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Clinical Trial Results:
A Dose Escalation (Phase 1), and Dose Expansion (Phase 2/3) Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using an Adeno-Associated Viral Vector (AAV8) Encoding Retinitis Pigmentosa GTPase Regulator (RPGR)

Summary
EudraCT number	2016-003852-60
Trial protocol	GB
Global end of trial date	18 Nov 2020

Results information
Results version number	v2(current)
This version publication date	20 Jun 2021
First version publication date	02 Jun 2021
Other versions	v1
Version creation reason	Correction of full data set Update in justification to the outcome measure.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

274RP101 (NSR-RPGR-01)

ISRCTN number

US NCT number

NCT03116113

WHO universal trial number (UTN)

Sponsor organisation name

Biogen

Sponsor organisation address

225 Binney Street, Cambridge, United States, 02142

Public contact

Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com

Scientific contact

Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-002601-PIP01-19

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

24 Mar 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Nov 2020

Was the trial ended prematurely?

Main objective of the trial

The objective of the study is to evaluate the safety, tolerability and efficacy of a single sub-retinal injection of BIIB112 in subjects with X-linked retinitis pigmentosa (XLRP).

Protection of trial subjects

Written informed consent was obtained from each subject or subject’s legally authorized representative (e.g., legal guardian), as applicable, prior to evaluations performed for eligibility. Subjects or the subject’s legally authorized representative were given adequate time to review the information in the informed consent/assent and were allowed to ask, and have answered, questions concerning all portions of the conduct of the study.

Background therapy

In Part I, all subjects were prescribed to take 1 milligram per kilogram per day (mg/kg/day) prednisone/prednisolone for a total of 10 days (beginning 2 days before the vector injection, on the day of injection, and then for 7 days); followed by 0.5 mg/kg/day for 7 days; 0.25 mg/kg/day for 2 days; and 0.125 mg/kg/day for 2 days (21 days in total). In Part II subjects in treated groups were given a 9-week course of oral prednisone/prednisolone and instructed to start taking the drug 3 days before Visit 2.

Evidence for comparator

Actual start date of recruitment

16 Mar 2017

Long term follow-up planned

Yes

Long term follow-up rationale

Efficacy, Safety

Long term follow-up duration

5 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 25

Country: Number of subjects enrolled

United Kingdom: 25

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Subjects were enrolled at investigational sites in the United Kingdom (UK) and the United States (US) from 16 March, 2017 to 18 November, 2020.

Screening details

A total of 50 subjects with X-Linked Retinitis Pigmentosa (XLRP) were randomised in the study and received treatment (18 subjects in Part 1 and 32 subjects in Part 2). Of these, 47 subjects completed the study (18 subjects in Part 1 and 29 in Part 2).

Period 1 title

Overall Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Data analyst, Assessor

Blinding implementation details

Part 1 of the study was open label and Part II was double-masked to the assigned dose, and open-label with respect to the treatment procedure. Primary efficacy endpoint data for Part 2 was also masked.

Are arms mutually exclusive

Yes

Part 1: BIIB112 Dose 1

Arm description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 1 (5 × 10^9 vector genomes {vg}) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Arm type

Experimental

Investigational medicinal product name

BIIB112

Investigational medicinal product code

Other name

AAV8-RPGR

Pharmaceutical forms

Suspension for injection

Routes of administration

Intraocular use

Dosage and administration details

Single, subretinal injection, Day 0.

Part 1: BIIB112 Dose 2

Arm description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 2 (1 × 10^10 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Arm type

Experimental

Investigational medicinal product name

BIIB112

Investigational medicinal product code

Other name

AAV8-RPGR

Pharmaceutical forms

Suspension for injection

Routes of administration

Intraocular use

Dosage and administration details

Single, subretinal injection, Day 0.

Part 1: BIIB112 Dose 3

Arm description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 3 (5 × 10^10 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Arm type

Experimental

Investigational medicinal product name

BIIB112

Investigational medicinal product code

Other name

AAV8-RPGR

Pharmaceutical forms

Suspension for injection

Routes of administration

Intraocular use

Dosage and administration details

Single, subretinal injection, Day 0.

Part 1: BIIB112 Dose 4

Arm description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 4 (1 × 10^11 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Arm type

Experimental

Investigational medicinal product name

BIIB112

Investigational medicinal product code

Other name

AAV8-RPGR

Pharmaceutical forms

Suspension for injection

Routes of administration

Intraocular use

Dosage and administration details

Single, subretinal injection, Day 0.

Part 1: BIIB112 Dose 5

Arm description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 5 (2.5 × 10^11 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Arm type

Experimental

Investigational medicinal product name

BIIB112

Investigational medicinal product code

Other name

AAV8-RPGR

Pharmaceutical forms

Suspension for injection

Routes of administration

Intraocular use

Dosage and administration details

Single, subretinal injection, Day 0.

Part 1: BIIB112 Dose 6

Arm description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 6 (5 × 10^11 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Arm type

Experimental

Investigational medicinal product name

BIIB112

Investigational medicinal product code

Other name

AAV8-RPGR

Pharmaceutical forms

Suspension for injection

Routes of administration

Intraocular use

Dosage and administration details

Single, subretinal injection, Day 0.

Part 2: Untreated Group

Arm description

Subjects received no intervention to allow for a controlled comparison.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Part 2: BIIB112 Low Dose

Arm description

Followed by vitrectomy and retinal detachment in study eye, subjects received a single low dose (5 × 10^10 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Arm type

Experimental

Investigational medicinal product name

BIIB112

Investigational medicinal product code

Other name

AAV8-RPGR

Pharmaceutical forms

Suspension for injection

Routes of administration

Intraocular use

Dosage and administration details

Single, subretinal injection, Day 0.

Part 2: BIIB112 High Dose

Arm description

Followed by vitrectomy and retinal detachment in study eye, subjects received a single high dose (2.5 × 10^11 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Arm type

Experimental

Investigational medicinal product name

BIIB112

Investigational medicinal product code

Other name

AAV8-RPGR

Pharmaceutical forms

Suspension for injection

Routes of administration

Intraocular use

Dosage and administration details

Single, subretinal injection, Day 0.

Number of subjects in period 1	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Started	3	3	3	3	3	3	9	11	12
Completed	3	3	3	3	3	3	9	10	10
Not completed	0	0	0	0	0	0	0	1	2
Withdrew due to COVID-19	-	-	-	-	-	-	-	1	2

Baseline characteristics

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Reporting group title

Part 1: BIIB112 Dose 1

Reporting group description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 1 (5 × 10^9 vector genomes {vg}) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 1: BIIB112 Dose 2

Reporting group description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 2 (1 × 10^10 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 1: BIIB112 Dose 3

Reporting group description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 3 (5 × 10^10 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 1: BIIB112 Dose 4

Reporting group description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 4 (1 × 10^11 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 1: BIIB112 Dose 5

Reporting group description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 5 (2.5 × 10^11 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 1: BIIB112 Dose 6

Reporting group description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 6 (5 × 10^11 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 2: Untreated Group

Reporting group description

Subjects received no intervention to allow for a controlled comparison.

Reporting group title

Part 2: BIIB112 Low Dose

Reporting group description

Followed by vitrectomy and retinal detachment in study eye, subjects received a single low dose (5 × 10^10 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 2: BIIB112 High Dose

Reporting group description

Followed by vitrectomy and retinal detachment in study eye, subjects received a single high dose (2.5 × 10^11 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose	Total
Number of subjects	3	3	3	3	3	3	9	11	12	50
Age Categorical
Units: subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	36.3 ( 6.35 )	34.3 ( 10.69 )	30.0 ( 2.65 )	33.3 ( 14.57 )	25.0 ( 5.00 )	32.3 ( 15.31 )	33.7 ( 13.83 )	30.6 ( 8.83 )	26.8 ( 7.11 )	-
Gender Categorical
Units: subjects
Female	0	0	0	0	0	0	0	0	0	0
Male	3	3	3	3	3	3	9	11	12	50
Ethnicity
Units: Subjects
Hispanic or Latino	0	0	0	0	0	1	2	3	5	11
Not Hispanic or Latino	3	3	3	3	3	2	7	8	7	39
Race
Units: Subjects
White	3	3	3	3	3	3	6	9	12	45
Black, of African Heritage	0	0	0	0	0	0	0	1	0	1
Asian	0	0	0	0	0	0	0	1	0	1
Multiple	0	0	0	0	0	0	1	0	0	1
Other	0	0	0	0	0	0	2	0	0	2

End points

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Reporting group title

Part 1: BIIB112 Dose 1

Reporting group description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 1 (5 × 10^9 vector genomes {vg}) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 1: BIIB112 Dose 2

Reporting group description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 2 (1 × 10^10 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 1: BIIB112 Dose 3

Reporting group description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 3 (5 × 10^10 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 1: BIIB112 Dose 4

Reporting group description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 4 (1 × 10^11 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 1: BIIB112 Dose 5

Reporting group description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 5 (2.5 × 10^11 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 1: BIIB112 Dose 6

Reporting group description

Followed by vitrectomy and retinal detachment in the study eye, subjects received a single Dose 6 (5 × 10^11 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 2: Untreated Group

Reporting group description

Subjects received no intervention to allow for a controlled comparison.

Reporting group title

Part 2: BIIB112 Low Dose

Reporting group description

Followed by vitrectomy and retinal detachment in study eye, subjects received a single low dose (5 × 10^10 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Reporting group title

Part 2: BIIB112 High Dose

Reporting group description

Followed by vitrectomy and retinal detachment in study eye, subjects received a single high dose (2.5 × 10^11 vg) of BIIB112 by sub-retinal injection on Day 0 (surgery day).

Primary: Part 1: Number of Subjects with Dose-Limiting Toxicities (DLTs)

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End point title

Part 1: Number of Subjects with Dose-Limiting Toxicities (DLTs) ^[1] ^[2]

End point description

DLTs are defined as any of the following events considered to be related to AAV8-RPGR: Sustained decrease in best-corrected visual acuity (BCVA) of ≥30 letters on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart compared to baseline (sustained is defined as lasting 48 hours or more until recovery, with recovery defined as visual acuity (VA) returning to within 10 letters of baseline VA. An exception is made for surgery-related events occurring in close temporal association {within <24 hours} of the surgery); Vitreous inflammation, vitritis (>Grade 3 using standardised Nussenblatt vitreous inflammation scale grading); Any clinically significant retinal damage observed that is not directly attributed to complications of surgery; Any clinically relevant suspected unexpected serious adverse reaction, with the exception of vision loss or vision threatening. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Primary

End point timeframe

Up to Month 24

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: subjects	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Part 1: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

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End point title

Part 1: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs) ^[3] ^[4]

End point description

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Primary

End point timeframe

Up to Month 24

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: subjects	3	3	3	3	3	3

No statistical analyses for this end point

Primary: Part 2: Percentage of Study Eyes with ≥7 Decibels (dB) Improvement from Baseline at ≥5 of the 16 Central Loci of the 10-2 Grid Assessed by Macular Integrity Assessment (MAIA) Microperimetry

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End point title

Part 2: Percentage of Study Eyes with ≥7 Decibels (dB) Improvement from Baseline at ≥5 of the 16 Central Loci of the 10-2 Grid Assessed by Macular Integrity Assessment (MAIA) Microperimetry ^[5]

End point description

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as ‘< 0’, ‘0’, or a positive integer. The point labelled as ‘< 0’ was assigned a value of ‘-1’ by MAIA in the calculation. Improvement in Retinal Sensitivity in center grid was defined as an increase from baseline of 7 or more decibels in any 5 or more points out of the 16 central points. Intent-to-treat (ITT) analysis set included all subjects that were randomised under the 3-arm randomisation schedules.

End point type

Primary

End point timeframe

Month 12

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9 ^[6]	8 ^[7]	8 ^[8]
Units: percentage of study eyes
number (confidence interval 80%)	22.2 (6.1 to 49.0)	37.5 (14.7 to 65.5)	25.0 (6.9 to 53.8)

Notes
[6] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[7] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[8] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

Untreated Group Vs BIIB112 Low Dose

Comparison groups

Part 2: Untreated Group v Part 2: BIIB112 Low Dose

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3181

Method

Fisher’s Exact-Boschloo test

Parameter type

Difference from Untreated Group

Confidence interval

level

80%

sides

2-sided

lower limit

-13.9

upper limit

Untreated Group Vs BIIB112 High Dose

Comparison groups

Part 2: Untreated Group v Part 2: BIIB112 High Dose

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5177

Method

Fisher’s Exact-Boschloo test

Parameter type

Difference from Untreated Group

Confidence interval

level

80%

sides

2-sided

lower limit

-24.4

upper limit

30.5

Primary: Part 2: Number of Subjects with TEAEs

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End point title

Part 2: Number of Subjects with TEAEs ^[9] ^[10]

End point description

End point type

Primary

End point timeframe

Up to Month 12

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	11	12
Units: subjects	5	11	12

No statistical analyses for this end point

Secondary: Part 1: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 out of the 16 Central Loci in Microperimetry

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End point title

Part 1: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 out of the 16 Central Loci in Microperimetry ^[11]

End point description

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as ‘< 0’, ‘0’ or a positive integer. The point labelled as ‘< 0’ was assigned a value of ‘-1’ by MAIA in the calculation. Improvement in Retinal Sensitivity in center grid was defined as an increase from baseline of 7 or more decibels in any 5 or more points out of the 16 central points. Safety analysis set consists of all subjects who received study treatment (vitrectomy/AAV8-RPGR). n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3 ^[12]	2 ^[13]	3 ^[14]	3 ^[15]	3 ^[16]	3 ^[17]
Units: percentage of study eyes
number (confidence interval 95%)
Month 1 (n=3,2,3,3,3,3)	0.0 (0.0 to 70.8)	0.0 (0.0 to 84.2)	100.0 (29.2 to 100.0)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 3 (n=3,2,3,3,3,3)	0.0 (0.0 to 70.8)	0.0 (0.0 to 84.2)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 6 (n=3,2,3,3,3,3)	0.0 (0.0 to 70.8)	0.0 (0.0 to 84.2)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 9 (n=3,2,3,3,3,3)	0.0 (0.0 to 70.8)	0.0 (0.0 to 84.2)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 12 (n=3,2,3,3,2,3)	0.0 (0.0 to 70.8)	0.0 (0.0 to 84.2)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	50.0 (1.3 to 98.7)	33.3 (0.8 to 90.6)
Month 18 (n=3,2,3,3,3,2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 84.2)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 84.2)
Month 24 (n=3,1,3,3,3,3)	0.0 (0.0 to 70.8)	0.0 (0.0 to 97.5)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)

Notes
[12] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[13] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[14] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[15] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[16] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[17] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

No statistical analyses for this end point

Secondary: Part 1: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 Out of the 68 Loci in Microperimetry

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End point title

Part 1: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 Out of the 68 Loci in Microperimetry ^[18]

End point description

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as ‘< 0’, ‘0’ or a positive integer. The point labelled as ‘< 0’ was assigned a value of ‘-1’ by MAIA in the calculation. Improvement in Retinal Sensitivity in whole grid was defined as an increase from baseline of 7 or more decibels in any 5 or more points of the grid as a whole (68 points). Safety analysis set consists of all subjects who received study treatment (vitrectomy/AAV8-RPGR). n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3 ^[19]	2 ^[20]	3 ^[21]	3 ^[22]	3 ^[23]	3 ^[24]
Units: percentage of study eyes
number (confidence interval 95%)
Month 1 (n=3,2,3,3,3,3)	0.0 (0.0 to 70.8)	0.0 (0.0 to 84.2)	100.0 (29.2 to 100.0)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 3 (n=3,2,3,3,3,3)	0.0 (0.0 to 70.8)	0.0 (0.0 to 84.2)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)
Month 6 (n=3,2,3,3,3,3)	0.0 (0.0 to 70.8)	0.0 (0.0 to 84.2)	100.0 (29.2 to 100.0)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)
Month 9 (n=3,2,3,3,3,3)	0.0 (0.0 to 70.8)	0.0 (0.0 to 84.2)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)
Month 12 (n=3,2,3,3,2,3)	0.0 (0.0 to 70.8)	50.0 (1.3 to 98.7)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)	50.0 (1.3 to 98.7)	66.7 (9.4 to 99.2)
Month 18 (n=3,2,3,3,3,2)	0.0 (0.0 to 70.8)	50.0 (1.3 to 98.7)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)	50.0 (1.3 to 98.7)
Month 24 (n=3,1,3,3,3,3)	0.0 (0.0 to 70.8)	0.0 (0.0 to 97.5)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)

Notes
[19] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[20] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[21] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[22] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[23] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[24] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Mean Sensitivity of the 16 Central Loci

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End point title

Part 1: Change from Baseline in Mean Sensitivity of the 16 Central Loci ^[25]

End point description

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as ‘< 0’, ‘0’ or a positive integer. The point labelled as ‘< 0’ is assigned a value of ‘-1’ by MAIA in the calculation. Improvement in Retinal Sensitivity in center grid was defined as an increase from baseline of 7 or more decibels in any 5 or more points out of the 16 central points. Here negative values indicate a decline in retinal sensitivity. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR). 99999 indicates that standard deviation was not evaluable as there was only 1 subject. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Month 1, 3, 6, 9, 12, 18 and 24

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3 ^[26]	2 ^[27]	3 ^[28]	3 ^[29]	3 ^[30]	3 ^[31]
Units: decibel
arithmetic mean (standard deviation)
Baseline: Study Eye (n=3,2,3,3,3,3)	0.33 ( 1.748 )	1.78 ( 1.282 )	3.35 ( 0.911 )	6.52 ( 3.398 )	13.46 ( 6.316 )	7.75 ( 7.742 )
Baseline: Non-Study Eye (n=3,2,3,3,3,3)	0.23 ( 1.358 )	3.31 ( 2.563 )	6.92 ( 2.221 )	8.21 ( 5.570 )	13.71 ( 8.447 )	7.54 ( 7.542 )
Change at Month 1: Study Eye (n=3,2,3,3,3,3)	0.52 ( 0.477 )	-0.09 ( 0.928 )	6.10 ( 0.844 )	1.19 ( 6.094 )	-0.63 ( 4.154 )	-1.90 ( 7.686 )
Change at Month 1: Non-Study Eye (n=3,2,3,3,3,3)	0.42 ( 1.122 )	-0.81 ( 1.768 )	-0.98 ( 1.531 )	-0.19 ( 0.272 )	1.40 ( 2.690 )	0.19 ( 2.063 )
Change at Month 3: Study Eye (n=3,2,3,3,3,3)	0.40 ( 0.407 )	0.47 ( 1.282 )	5.63 ( 2.394 )	1.73 ( 8.714 )	-3.58 ( 7.476 )	-3.35 ( 2.894 )
Change at Month 3: Non-Study Eye (n=3,2,3,3,3,3)	-0.06 ( 0.534 )	-0.91 ( 0.575 )	-1.15 ( 2.094 )	0.33 ( 1.134 )	2.06 ( 1.137 )	-0.42 ( 0.289 )
Change at Month 6: Study Eye (n=3,2,3,3,3,3)	0.54 ( 0.485 )	-0.06 ( 0.265 )	5.10 ( 1.890 )	3.25 ( 8.199 )	-2.38 ( 5.177 )	0.85 ( 5.105 )
Change at Month 6: Non-Study Eye (n=3,2,3,3,3,3)	-0.17 ( 0.344 )	-0.34 ( 2.607 )	-1.19 ( 1.535 )	2.10 ( 3.437 )	2.19 ( 0.933 )	-0.65 ( 1.156 )
Change at Month 9: Study Eye (n=3,2,3,3,3,3)	0.21 ( 0.219 )	0.09 ( 1.282 )	4.65 ( 3.851 )	3.69 ( 6.308 )	-2.50 ( 5.314 )	0.77 ( 7.096 )
Change at Month 9: Non-Study Eye (n=3,2,3,3,3,3)	-0.35 ( 0.509 )	0.19 ( 2.210 )	0.20 ( 2.751 )	-0.06 ( 1.789 )	2.52 ( 1.714 )	0.40 ( 2.032 )
Change at Month 12: Study Eye (n=3,2,3,3,2,3)	0.19 ( 0.272 )	0.13 ( 1.945 )	4.10 ( 2.908 )	3.98 ( 5.090 )	2.25 ( 2.121 )	0.56 ( 5.590 )
Change at Month 12: Non-Study Eye (n=3,2,3,3,2,3)	-0.10 ( 0.355 )	-1.09 ( 1.370 )	-1.02 ( 0.581 )	0.42 ( 1.951 )	2.31 ( 2.990 )	-0.29 ( 1.835 )
Change at Month 18: Study Eye (n=3,2,3,3,3,2)	0.21 ( 0.473 )	-1.13 ( 0.177 )	2.69 ( 2.507 )	2.92 ( 5.550 )	-2.79 ( 6.733 )	-1.09 ( 5.436 )
Change at Month 18: Non-Study Eye (n=3,2,3,3,3,2)	-0.33 ( 0.577 )	-1.09 ( 1.282 )	0.02 ( 0.940 )	-0.67 ( 0.806 )	1.92 ( 3.085 )	-0.59 ( 2.607 )
Change at Month 24: Study Eye (n=3,1,3,3,3,3)	0.04 ( 0.253 )	-1.88 ( 99999 )	2.75 ( 2.683 )	1.48 ( 5.236 )	-4.90 ( 5.250 )	-1.88 ( 5.862 )
Month 24: Non-Study Eye (n=3,1,3,3,3,3)	-0.46 ( 0.469 )	-1.63 ( 99999 )	-0.33 ( 1.347 )	-0.56 ( 1.207 )	0.71 ( 3.263 )	-2.19 ( 2.189 )

Notes
[26] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[27] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[28] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[29] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[30] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[31] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Mean Sensitivity of the 68 Central Loci

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End point title

Part 1: Change from Baseline in Mean Sensitivity of the 68 Central Loci ^[32]

End point description

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as ‘< 0’, ‘0’ or a positive integer. The point labelled as ‘< 0’ is assigned a value of ‘-1’ by MAIA in the calculation. Improvement in Retinal Sensitivity in whole grid was defined as an increase from baseline of 7 or more decibels in any 5 or more points of the grid as a whole (68 points). Here negative values indicate a decline in retinal sensitivity. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR). 99999 indicates that standard deviation was not evaluable as there was only 1 subject. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Month 1, 3, 6, 9, 12, 18 and 24

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3 ^[33]	2 ^[34]	3 ^[35]	3 ^[36]	3 ^[37]	3 ^[38]
Units: decibel
arithmetic mean (standard deviation)
Baseline: Study Eye (n=3,2,3,3,3,3)	-0.19 ( 0.690 )	0.20 ( 0.281 )	0.21 ( 0.435 )	2.22 ( 1.536 )	8.87 ( 10.784 )	4.26 ( 6.732 )
Baseline: Non-Study Eye (n=3,2,3,3,3,3)	-0.38 ( 0.540 )	1.47 ( 1.061 )	1.50 ( 1.419 )	2.30 ( 1.559 )	9.11 ( 12.466 )	5.35 ( 8.579 )
Change at Month 1: Study Eye (n=3,2,3,3,3,3)	0.12 ( 0.309 )	0.24 ( 1.185 )	2.42 ( 0.283 )	0.08 ( 2.436 )	0.56 ( 3.243 )	-1.69 ( 4.341 )
Change at Month 1: Non-Study Eye (n=3,2,3,3,3,3)	0.18 ( 0.481 )	-0.76 ( 1.165 )	-0.08 ( 0.938 )	-0.11 ( 0.111 )	1.24 ( 1.639 )	-0.66 ( 1.474 )
Change at Month 3: Study Eye (n=3,2,3,3,3,3)	0.14 ( 0.137 )	0.74 ( 1.820 )	2.44 ( 1.564 )	0.58 ( 5.061 )	-1.87 ( 4.073 )	-0.60 ( 1.383 )
Change at Month 3: Non-Study Eye (n=3,2,3,3,3,3)	-0.06 ( 0.292 )	-0.29 ( 1.549 )	-0.29 ( 1.351 )	0.68 ( 1.223 )	1.38 ( 1.005 )	-0.65 ( 0.407 )
Change at Month 6: Study Eye (n=3,2,3,3,3,3)	0.04 ( 0.334 )	0.19 ( 0.957 )	2.28 ( 1.534 )	0.90 ( 5.011 )	-0.60 ( 1.596 )	0.51 ( 2.154 )
Change at Month 6: Non-Study Eye (n=3,2,3,3,3,3)	-0.24 ( 0.331 )	-0.32 ( 1.872 )	-0.51 ( 0.773 )	3.86 ( 5.648 )	1.76 ( 0.470 )	-0.84 ( 1.101 )
Change at Month 9: Study Eye (n=3,2,3,3,3,3)	-0.18 ( 0.145 )	0.31 ( 1.456 )	2.02 ( 2.177 )	0.90 ( 4.233 )	-0.87 ( 2.229 )	-0.13 ( 4.044 )
Change at Month 9: Non-Study Eye (n=3,2,3,3,3,3)	-0.37 ( 0.467 )	-0.12 ( 1.830 )	1.66 ( 1.790 )	0.77 ( 1.405 )	2.05 ( 0.816 )	-0.41 ( 1.157 )
Change at Month 12: Study Eye (n=3,2,3,3,2,3)	-0.16 ( 0.165 )	0.30 ( 1.612 )	1.72 ( 1.892 )	1.28 ( 3.541 )	-0.22 ( 2.600 )	-0.41 ( 4.208 )
Change at Month 12: Non-Study Eye (n=3,2,3,3,2,3)	-0.30 ( 0.417 )	-0.46 ( 1.633 )	-0.24 ( 0.153 )	0.76 ( 1.345 )	1.72 ( 1.144 )	-0.82 ( 1.248 )
Change at Month 18: Study Eye (n=3,2,3,3,3,2)	-0.23 ( 0.213 )	-0.50 ( 0.458 )	1.16 ( 1.144 )	1.37 ( 4.233 )	-0.72 ( 1.253 )	-1.32 ( 4.721 )
Change at Month 18: Non-Study Eye (n=3,2,3,3,3,2)	-0.33 ( 0.412 )	-0.57 ( 1.435 )	0.07 ( 0.509 )	0.18 ( 0.191 )	1.24 ( 1.265 )	-1.19 ( 2.267 )
Change at Month 24: Study Eye (n=3,1,3,3,3,3)	-0.40 ( 0.382 )	-0.96 ( 99999 )	1.17 ( 1.190 )	0.98 ( 3.510 )	-2.37 ( 1.225 )	-2.26 ( 6.009 )
Change at Month 24: Non-Study Eye (n=3,1,3,3,3,3)	-0.37 ( 0.427 )	-1.44 ( 99999 )	0.14 ( 0.221 )	0.24 ( 0.153 )	0.75 ( 1.427 )	-1.73 ( 2.481 )

Notes
[33] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[34] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[35] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[36] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[37] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[38] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Best Corrected Visual Acuity (BCVA) Score

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End point title

Part 1: Change from Baseline in Best Corrected Visual Acuity (BCVA) Score ^[39]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. Here negative values indicate decline in BCVA. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Baseline, Month 1, 3, 6, 9, 12, 18 and 24

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: letters
arithmetic mean (standard deviation)
Baseline: Study Eye	27.67 ( 8.145 )	49.67 ( 9.452 )	64.33 ( 7.095 )	63.67 ( 20.551 )	70.67 ( 4.163 )	67.33 ( 15.044 )
Baseline: Non-Study Eye	60.67 ( 2.082 )	57.33 ( 5.686 )	66.33 ( 2.517 )	62.67 ( 22.279 )	73.33 ( 4.163 )	75.00 ( 4.583 )
Change at Month 1: Study Eye	3.67 ( 3.055 )	0.33 ( 2.517 )	-1.00 ( 1.732 )	-1.33 ( 6.506 )	-0.67 ( 4.041 )	-0.67 ( 10.693 )
Change at Month 1: Non-Study Eye	3.00 ( 3.000 )	1.00 ( 4.359 )	1.00 ( 1.000 )	0.33 ( 0.577 )	2.00 ( 4.583 )	-2.67 ( 1.155 )
Change at Month 3: Study Eye	6.33 ( 2.309 )	0.00 ( 3.606 )	0.67 ( 2.082 )	1.67 ( 4.726 )	0.33 ( 6.028 )	0.67 ( 6.506 )
Change at Month 3: Non-Study Eye	3.00 ( 1.000 )	1.67 ( 1.528 )	-1.67 ( 1.528 )	2.33 ( 2.309 )	4.67 ( 4.509 )	-0.33 ( 0.577 )
Change at Month 6: Study Eye	5.00 ( 1.000 )	-3.67 ( 3.786 )	0.33 ( 0.577 )	3.67 ( 5.686 )	-3.67 ( 8.737 )	-0.67 ( 5.033 )
Change at Month 6: Non-Study Eye	-1.00 ( 7.211 )	-0.67 ( 4.726 )	-0.33 ( 3.215 )	3.67 ( 3.055 )	4.00 ( 4.359 )	-0.67 ( 1.528 )
Change at Month 9: Study Eye	1.33 ( 4.619 )	-0.67 ( 0.577 )	1.33 ( 4.509 )	4.00 ( 5.292 )	-3.67 ( 16.073 )	-2.33 ( 9.074 )
Change at Month 9: Non-Study Eye	-5.00 ( 5.292 )	-0.67 ( 5.033 )	1.00 ( 1.000 )	3.00 ( 3.606 )	5.67 ( 8.622 )	2.00 ( 4.359 )
Change at Month 12: Study Eye	4.67 ( 4.509 )	-2.00 ( 3.464 )	0.67 ( 5.132 )	4.33 ( 4.933 )	-15.00 ( 40.286 )	-2.33 ( 8.327 )
Change at Month 12: Non-Study Eye	-1.67 ( 2.309 )	-0.33 ( 3.215 )	-0.33 ( 0.577 )	2.00 ( 4.359 )	6.67 ( 6.429 )	1.00 ( 2.000 )
Change at Month 18: Study Eye	3.00 ( 8.718 )	-2.00 ( 3.606 )	-3.33 ( 5.132 )	3.33 ( 3.786 )	-9.33 ( 28.919 )	-5.00 ( 8.544 )
Change at Month 18: Non-Study Eye	-4.00 ( 6.245 )	0.00 ( 5.000 )	-0.33 ( 2.517 )	1.33 ( 2.517 )	5.00 ( 7.810 )	-0.33 ( 5.508 )
Change at Month 24: Study Eye	-2.00 ( 15.588 )	-2.00 ( 5.292 )	-3.33 ( 3.215 )	5.00 ( 7.000 )	-13.33 ( 32.747 )	-5.67 ( 6.110 )
Change at Month 24: Non-Study Eye	-3.67 ( 5.508 )	0.67 ( 0.577 )	-2.33 ( 1.528 )	2.33 ( 4.509 )	2.00 ( 7.810 )	-2.00 ( 3.000 )

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Low Luminance Visual Acuity (LLVA) Score

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End point title

Part 1: Change from Baseline in Low Luminance Visual Acuity (LLVA) Score ^[40]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. Here negative values indicate decline in LLVA. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Baseline, Month 1, 3, 6, 9. 12. 18 and 24

Notes
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	0 ^[41]	0 ^[42]	2 ^[43]	3 ^[44]	3 ^[45]	3 ^[46]
Units: letters
arithmetic mean (standard deviation)
Baseline: Study Eye	( )	( )	41.00 ( 18.385 )	34.33 ( 29.939 )	58.00 ( 3.000 )	41.67 ( 34.646 )
Baseline: Non-Study Eye	( )	( )	37.50 ( 24.749 )	37.67 ( 32.808 )	61.00 ( 2.646 )	57.33 ( 14.844 )
Change at Month 1: Study Eye	( )	( )	10.00 ( 9.899 )	0.33 ( 0.577 )	3.00 ( 5.292 )	4.67 ( 26.502 )
Change at Month 1: Non-Study Eye	( )	( )	10.00 ( 18.385 )	-0.33 ( 7.506 )	3.00 ( 5.196 )	-4.33 ( 7.572 )
Change at Month 3: Study Eye	( )	( )	14.00 ( 11.314 )	7.33 ( 6.658 )	-14.33 ( 38.214 )	-7.67 ( 10.263 )
Change at Month 3: Non-Study Eye	( )	( )	10.00 ( 16.971 )	1.00 ( 1.000 )	3.00 ( 4.583 )	2.00 ( 3.464 )
Change at Month 6: Study Eye	( )	( )	11.50 ( 7.778 )	8.33 ( 7.234 )	-16.67 ( 35.810 )	7.33 ( 9.713 )
Change at Month 6: Non-Study Eye	( )	( )	8.00 ( 15.556 )	1.67 ( 2.887 )	5.33 ( 1.155 )	0.67 ( 3.215 )
Change at Month 9: Study Eye	( )	( )	0.50 ( 4.950 )	10.00 ( 6.557 )	-14.33 ( 37.820 )	4.33 ( 8.083 )
Change at Month 9: Non-Study Eye	( )	( )	0.50 ( 4.950 )	2.00 ( 4.359 )	2.00 ( 3.464 )	3.33 ( 2.309 )
Change at Month 12: Study Eye	( )	( )	3.50 ( 0.707 )	16.00 ( 13.454 )	-11.33 ( 40.612 )	8.33 ( 11.590 )
Change at Month 12: Non-Study Eye	( )	( )	7.00 ( 9.899 )	6.67 ( 8.327 )	9.00 ( 4.359 )	4.00 ( 6.083 )
Change at Month 18: Study Eye	( )	( )	6.50 ( 7.778 )	10.67 ( 8.622 )	-12.33 ( 40.079 )	8.33 ( 5.508 )
Change at Month 18: Non-Study Eye	( )	( )	9.00 ( 21.213 )	2.33 ( 2.517 )	5.67 ( 4.726 )	-4.33 ( 7.234 )
Change at Month 24: Study Eye	( )	( )	3.00 ( 8.485 )	9.33 ( 14.295 )	-14.67 ( 38.371 )	-1.67 ( 6.506 )
Change at Month 24: Non-Study Eye	( )	( )	5.50 ( 24.749 )	0.67 ( 4.041 )	3.33 ( 3.512 )	-12.67 ( 11.547 )

Notes
[41] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[42] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[43] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[44] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[45] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[46] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with a ≥15 Letters Increase from Baseline for BCVA

Top of page

End point title

Part 1: Percentage of Eyes with a ≥15 Letters Increase from Baseline for BCVA ^[47]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 1: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 12: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 12: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 18: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 18: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 24: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 24: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with a ≥15 Letters Increase from Baseline for LLVA

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End point title

Part 1: Percentage of Eyes with a ≥15 Letters Increase from Baseline for LLVA ^[48]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	0 ^[49]	0 ^[50]	2 ^[51]	3 ^[52]	3 ^[53]	3 ^[54]
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 1: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 6: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 12: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 12: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 18: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 18: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 24: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 24: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)

Notes
[49] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[50] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[51] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[52] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[53] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[54] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with a ≥10 Letters Increase from Baseline for BCVA

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End point title

Part 1: Percentage of Eyes with a ≥10 Letters Increase from Baseline for BCVA ^[55]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 1: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 12: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 12: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 18: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 18: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 24: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 24: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with a ≥10 Letters Increase from Baseline for LLVA

Top of page

End point title

Part 1: Percentage of Eyes with a ≥10 Letters Increase from Baseline for LLVA ^[56]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	0 ^[57]	0 ^[58]	2 ^[59]	3 ^[60]	3 ^[61]	3 ^[62]
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	66.7 (9.4 to 99.2)
Month 1: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 3: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	66.7 (9.4 to 99.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 6: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 9: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 12: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)
Month 12: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 18: Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 18: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 24: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 24: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)

Notes
[57] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[58] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[59] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[60] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[61] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[62] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with a ≥5 Letters Increase from Baseline for BCVA

Top of page

End point title

Part 1: Percentage of Eyes with a ≥5 Letters Increase from Baseline for BCVA ^[63]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18, and 24

Notes
[63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	66.7 (9.4 to 99.2)
Month 1: Non-Study Eye	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 3: Study Eye	100.0 (29.2 to 100.0)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 3: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)	0.0 (0.0 to 70.8)
Month 6: Study Eye	66.7 (9.4 to 99.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 6: Non-Study Eye	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 9: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 9: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 12: Study Eye	66.7 (9.4 to 99.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 12: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 18: Study Eye	66.7 (9.4 to 99.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 18: Non-Study Eye	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 24: Study Eye	66.7 (9.4 to 99.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 24: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with a ≥5 Letters Increase from Baseline for LLVA

Top of page

End point title

Part 1: Percentage of Eyes with a ≥5 Letters Increase from Baseline for LLVA ^[64]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	0 ^[65]	0 ^[66]	2 ^[67]	3 ^[68]	3 ^[69]	3 ^[70]
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)
Month 1: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 3: Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 3: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 6: Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)
Month 6: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)	0.0 (0.0 to 70.8)
Month 9: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)
Month 9: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 12: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)
Month 12: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	33.3 (0.8 to 90.6)	100.0 (29.2 to 100.0)	33.3 (0.8 to 90.6)
Month 18: Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)
Month 18: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 24: Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 24: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)

Notes
[65] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[66] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[67] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[68] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[69] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[70] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with a ≥15 Letters Loss from Baseline for BCVA

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End point title

Part 1: Percentage of Eyes with a ≥15 Letters Loss from Baseline for BCVA ^[71]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 1: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 9: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 12: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 12: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 18: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 18: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 24: Study Eye	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 24: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with a ≥15 Letters Loss from Baseline for LLVA

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End point title

Part 1: Percentage of Eyes with a ≥15 Letters Loss from Baseline for LLVA ^[72]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	0 ^[73]	0 ^[74]	2 ^[75]	3 ^[76]	3 ^[77]	3 ^[78]
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 1: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 3: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 6: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 9: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 12: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 12: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 18: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 18: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 24: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 24: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)

Notes
[73] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[74] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[75] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[76] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[77] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[78] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with a ≥10 Letters Loss from Baseline for BCVA

Top of page

End point title

Part 1: Percentage of Eyes with a ≥10 Letters Loss from Baseline for BCVA ^[79]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[79] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 1: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 6: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 9: Non-Study Eye	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 12: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 12: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 18: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 18: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 24: Study Eye	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 24: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with a ≥10 Letters Loss from Baseline for LLVA

Top of page

End point title

Part 1: Percentage of Eyes with a ≥10 Letters Loss from Baseline for LLVA ^[80]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	0 ^[81]	0 ^[82]	2 ^[83]	3 ^[84]	3 ^[85]	3 ^[86]
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 1: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 3: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 3: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 6: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 9: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 12: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 12: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 18: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 18: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 24: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 24: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)

Notes
[81] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[82] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[83] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[84] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[85] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[86] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with a ≥5 Letters Loss from Baseline for BCVA

Top of page

End point title

Part 1: Percentage of Eyes with a ≥5 Letters Loss from Baseline for BCVA ^[87]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[87] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 1: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 3: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 3: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Study Eye	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)
Month 6: Non-Study Eye	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 9: Non-Study Eye	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 12: Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)
Month 12: Non-Study Eye	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 18: Study Eye	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)
Month 18: Non-Study Eye	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 24: Study Eye	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)
Month 24: Non-Study Eye	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with a ≥5 Letters Loss from Baseline for LLVA

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End point title

Part 1: Percentage of Eyes with a ≥5 Letters Loss from Baseline for LLVA ^[88]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	0 ^[89]	0 ^[90]	2 ^[91]	3 ^[92]	3 ^[93]	3 ^[94]
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 1: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)
Month 3: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)
Month 3: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 6: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 6: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 9: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 9: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 12: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 12: Non-Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)
Month 18: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	0.0 (0.0 to 70.8)
Month 18: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	66.7 (9.4 to 99.2)
Month 24: Study Eye	( to )	( to )	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)
Month 24: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	0.0 (0.0 to 70.8)	0.0 (0.0 to 70.8)	100.0 (29.2 to 100.0)

Notes
[89] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[90] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[91] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[92] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[93] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[94] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with Change from Baseline > -5 Letters for BCVA

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End point title

Part 1: Percentage of Eyes with Change from Baseline > -5 Letters for BCVA ^[95]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[95] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: percentage of eyes
number (confidence interval 95%)
Month 1: Study Eye	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)
Month 1: Non-Study Eye	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)
Month 3: Study Eye	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)
Month 3: Non-Study Eye	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)
Month 6: Study Eye	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)
Month 6: Non-Study Eye	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)
Month 9: Study Eye	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)
Month 9: Non-Study Eye	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)
Month 12: Study Eye	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)
Month 12: Non-Study Eye	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)
Month 18: Study Eye	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)
Month 18: Non-Study Eye	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)
Month 24: Study Eye	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)
Month 24: Non-Study Eye	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Eyes with Change from Baseline > -5 Letters for LLVA

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End point title

Part 1: Percentage of Eyes with Change from Baseline > -5 Letters for LLVA ^[96]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR).

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, 12, 18 and 24

Notes
[96] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	0 ^[97]	0 ^[98]	2 ^[99]	3 ^[100]	3 ^[101]	3 ^[102]
Units: percentage of eyes
number (confidence interval 95%)
Change at Month 1: Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)
Change at Month 1: Non-Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)
Change at Month 3: Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	33.3 (0.8 to 90.6)
Change at Month 3: Non-Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)
Change at Month 6: Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)
Change at Month 6: Non-Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)
Change at Month 9: Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)
Change at Month 9: Non-Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)
Change at Month 12: Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)
Change at Month 12: Non-Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)
Change at Month 18: Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	100.0 (29.2 to 100.0)
Change at Month 18: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	33.3 (0.8 to 90.6)
Change at Month 24: Study Eye	( to )	( to )	100.0 (15.8 to 100.0)	100.0 (29.2 to 100.0)	66.7 (9.4 to 99.2)	66.7 (9.4 to 99.2)
Change at Month 24: Non-Study Eye	( to )	( to )	50.0 (1.3 to 98.7)	100.0 (29.2 to 100.0)	100.0 (29.2 to 100.0)	0.0 (0.0 to 70.8)

Notes
[97] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[98] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[99] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[100] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[101] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.
[102] - 'Number of subjects analysed' signifies number of subjects analysed in this endpoint.

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Central Ellipsoid Area

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End point title

Part 1: Change from Baseline in Central Ellipsoid Area ^[103]

End point description

Spectral Domain Optical Coherence Tomography (SD-OCT) was used to assess change in central ellipsoid area. Here negative values indicate decline in central ellipsoid area. Safety analysis included all subjects who received study treatment (vitrectomy/AAV8-RPGR). n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Month 1, 3, 6, 9, 12, 18 and 24

Notes
[103] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: millimeter square (mm^2)
arithmetic mean (standard deviation)
Baseline: Study Eye (n=3,3,3,3,3,3)	0.140 ( 0.1637 )	2.750 ( 4.7631 )	0.137 ( 0.1582 )	0.193 ( 0.1686 )	8.327 ( 13.8600 )	3.107 ( 5.2001 )
Baseline: Non-Study Eye (n=3,3,3,2,3,3)	0.130 ( 0.0985 )	2.313 ( 3.7500 )	0.093 ( 0.0814 )	0.465 ( 0.1061 )	14.307 ( 24.1914 )	5.257 ( 8.8720 )
Change at Month 1: Study Eye (n=3,3,3,3,3,3)	-0.077 ( 0.1159 )	-0.493 ( 0.8545 )	-0.103 ( 0.1050 )	-0.050 ( 0.0458 )	-1.360 ( 2.2863 )	-1.310 ( 2.2258 )
Change at Month 1: Non-Study Eye (n=3,3,3,2,3,3)	-0.060 ( 0.0265 )	-0.383 ( 0.4508 )	-0.020 ( 0.0693 )	-0.080 ( 0.0566 )	-0.410 ( 0.7645 )	0.873 ( 1.5824 )
Change at Month 3: Study Eye (n=3,3,3,3,2,3)	-0.100 ( 0.1249 )	-0.560 ( 0.9699 )	-0.110 ( 0.1153 )	-0.060 ( 0.0529 )	-2.255 ( 3.0335 )	-2.960 ( 5.0319 )
Change at Month 3: Non-Study Eye (n=3,3,3,2,3,2)	-0.093 ( 0.0404 )	-0.407 ( 0.4895 )	-0.043 ( 0.0379 )	-0.095 ( 0.0495 )	-0.407 ( 0.7778 )	-0.040 ( 0.0566 )
Change at Month 6: Study Eye (n=3,3,3,3,3,2)	-0.120 ( 0.1375 )	-0.527 ( 0.9122 )	-0.113 ( 0.1206 )	-0.070 ( 0.0624 )	-4.847 ( 8.1176 )	-0.055 ( 0.0778 )
Change at Month 6: Non-Study Eye (n=3,3,3,2,3,2)	-0.093 ( 0.0404 )	-0.410 ( 0.4951 )	-0.060 ( 0.0529 )	-0.120 ( 0.0424 )	-0.983 ( 1.7747 )	-0.050 ( 0.0707 )
Change at Month 9: Study Eye (n=3,3,3,3,3,3)	-0.127 ( 0.1419 )	-0.540 ( 0.9353 )	-0.117 ( 0.1258 )	-0.063 ( 0.0551 )	-5.640 ( 9.4830 )	-2.960 ( 5.0664 )
Change at Month 9: Non-Study Eye (n=3,3,3,2,3,2)	-0.097 ( 0.0451 )	-0.437 ( 0.5326 )	-0.063 ( 0.0569 )	-0.120 ( 0.0141 )	-1.100 ( 1.9504 )	-0.050 ( 0.0707 )
Change at Month 12: Study Eye (n=3,3,3,3,3,3)	-0.130 ( 0.1473 )	-0.560 ( 0.9699 )	-0.117 ( 0.1258 )	-0.053 ( 0.0551 )	-5.623 ( 9.4975 )	-3.007 ( 5.1386 )
Change at Month 12: Non-Study Eye (n=3,3,3,2,3,3)	-0.097 ( 0.0451 )	-0.447 ( 0.5353 )	-0.033 ( 0.1266 )	-0.120 ( 0.0424 )	-1.010 ( 2.0313 )	0.997 ( 1.8312 )
Change at Month 18: Study Eye (n=3,3,3,3,3,3)	-0.133 ( 0.1528 )	-0.567 ( 0.9815 )	-0.137 ( 0.1582 )	0.027 ( 0.1617 )	-5.633 ( 9.4975 )	-2.993 ( 5.1155 )
Change at Month 18: Non-Study Eye (n=3,3,3,2,3,3)	-0.113 ( 0.0709 )	-0.450 ( 0.5408 )	-0.027 ( 0.1201 )	-0.115 ( 0.0919 )	-1.107 ( 2.0124 )	0.590 ( 1.1364 )
Change at Month 24: Study Eye (n=3,3,3,3,3,3)	-0.133 ( 0.1528 )	-0.573 ( 0.9930 )	-0.137 ( 0.1582 )	0.010 ( 0.1552 )	-5.657 ( 9.5292 )	-3.010 ( 5.1357 )
Change at Month 24: Non-Study Eye (n=3,3,3,2,3,3)	-0.117 ( 0.0764 )	-0.443 ( 0.5297 )	-0.060 ( 0.0794 )	-0.150 ( 0.0283 )	-1.163 ( 2.0063 )	0.367 ( 0.7505 )

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Central Horizontal Ellipsoid Width

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End point title

Part 1: Change from Baseline in Central Horizontal Ellipsoid Width ^[104]

End point description

SD-OCT was used to assess change in central horizontal ellipsoid width. Here negative values indicate decline in central horizontal ellipsoid width. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR). n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Month 1, 3, 6, 9, 12, 18 and 24

Notes
[104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: Micron (um)
arithmetic mean (standard deviation)
Baseline: Study Eye (n=3,3,3,3,3,3)	162.67 ( 175.104 )	1375.33 ( 2382.147 )	248.00 ( 275.158 )	462.33 ( 400.775 )	2411.33 ( 3048.253 )	745.67 ( 774.448 )
Baseline: Non-Study Eye (n=3,3,3,2,3,3)	355.67 ( 280.878 )	1383.67 ( 2396.581 )	250.00 ( 223.139 )	792.00 ( 100.409 )	3341.00 ( 4556.473 )	937.67 ( 1088.262 )
Change at Month 1: Study Eye (n=3,3,3,3,3,3)	-56.33 ( 73.894 )	-311.00 ( 538.668 )	-174.00 ( 162.567 )	-26.33 ( 24.007 )	-203.33 ( 248.605 )	88.67 ( 422.044 )
Change at Month 1: Non-Study Eye (n=3,3,3,2,3,3)	-62.33 ( 40.216 )	-321.67 ( 557.143 )	47.33 ( 226.509 )	-56.00 ( 63.640 )	-14.00 ( 113.331 )	977.33 ( 1814.500 )
Change at Month 3: Study Eye (n=3,3,3,3,3,3)	-73.00 ( 70.193 )	-318.00 ( 550.792 )	-174.33 ( 163.022 )	-89.33 ( 125.644 )	-369.00 ( 271.070 )	-453.33 ( 554.795 )
Change at Month 3: Non-Study Eye (n=3,3,3,2,3,3)	-149.00 ( 80.988 )	-333.33 ( 577.350 )	-60.67 ( 78.258 )	-151.00 ( 15.556 )	-19.00 ( 123.503 )	1008.33 ( 1869.924 )
Change at Month 6: Study Eye (n=3,3,3,3,3,3)	-115.67 ( 105.624 )	-318.67 ( 551.947 )	-175.67 ( 164.852 )	-146.67 ( 129.454 )	-1070.67 ( 1365.685 )	-461.33 ( 553.453 )
Change at Month 6: Non-Study Eye (n=3,3,3,2,3,2)	-158.67 ( 65.033 )	-347.00 ( 601.022 )	-76.33 ( 79.135 )	-195.50 ( 6.364 )	-20.00 ( 144.503 )	-108.50 ( 153.442 )
Change at Month 9: Study Eye (n=3,3,3,3,3,3)	-127.00 ( 121.025 )	-321.33 ( 556.566 )	-178.33 ( 168.548 )	-149.00 ( 131.936 )	-1096.33 ( 1343.289 )	-441.00 ( 505.720 )
Change at Month 9: Non-Study Eye (n=3,3,3,2,3,2)	-175.00 ( 39.585 )	-348.00 ( 602.754 )	-77.33 ( 79.053 )	-202.50 ( 4.950 )	-81.67 ( 217.721 )	-124.00 ( 175.362 )
Change at Month 12: Study Eye (n=3,3,3,3,3,3)	-130.00 ( 125.300 )	-238.33 ( 412.805 )	-217.00 ( 225.980 )	-106.33 ( 132.666 )	-1055.33 ( 1394.128 )	-463.00 ( 537.199 )
Change at Month 12: Non-Study Eye (n=3,3,3,2,3,3)	-181.67 ( 30.665 )	-349.33 ( 605.063 )	-35.67 ( 255.895 )	-113.50 ( 47.376 )	-143.00 ( 221.007 )	1108.00 ( 2145.532 )
Change at Month 18: Study Eye (n=3,3,3,3,3,3)	-131.00 ( 126.740 )	-239.33 ( 414.537 )	-248.00 ( 275.158 )	21.67 ( 332.031 )	-1059.67 ( 1438.362 )	-461.67 ( 530.381 )
Change at Month 18: Non-Study Eye (n=3,3,3,2,3,3)	-316.67 ( 213.601 )	-354.67 ( 614.301 )	-168.67 ( 161.122 )	-188.00 ( 65.054 )	-113.00 ( 242.736 )	1078.67 ( 2094.819 )
Change at Month 24: Study Eye (n=3,3,3,3,3,3)	-131.33 ( 127.222 )	-242.33 ( 419.734 )	-248.00 ( 275.158 )	-43.33 ( 243.904 )	-1162.00 ( 1352.050 )	-465.67 ( 587.699 )
Change at Month 24: Non-Study Eye (n=3,3,3,2,3,3)	-329.33 ( 235.434 )	-358.00 ( 620.074 )	-145.67 ( 162.543 )	-254.50 ( 7.778 )	-159.67 ( 265.038 )	1065.67 ( 2074.136 )

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Fundus Autofluoroscence- Total Area of Preserved Autofluoroscence

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End point title

Part 1: Change from Baseline in Fundus Autofluoroscence- Total Area of Preserved Autofluoroscence ^[105]

End point description

Fundus Autofluoroscence was used to assess change in total area of preserved autofluoroscence. Here negative values indicate decline in total area of preserved autofluoroscence. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR). 99999 indicates that standard deviation was not evaluable as there was only 1 subject. 999999 indicates that data was not evaluable at given time point. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Month 1, 3, 6, 12, 18 and 24

Notes
[105] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: mm^2
arithmetic mean (standard deviation)
Baseline: Study Eye (n=1,0,0,0,0,0)	27.050 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Baseline: Non-Study Eye (n=1,0,1,0,0,0)	22.910 ( 99999 )	999999 ( 999999 )	50.640 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 1: Study Eye (n=1,0,0,0,0,0)	-1.820 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 1: Non-Study Eye (n=1,0,1,0,0,0)	-2.420 ( 99999 )	999999 ( 999999 )	-8.620 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 3: Study Eye (n=1,0,0,0,0,0)	-2.940 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 3: Non-Study Eye (n=1,0,1,0,0,0)	-2.650 ( 99999 )	999999 ( 999999 )	-5.150 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 6: Study Eye (n=1,0,0,0,0,0)	-3.460 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 6: Non-Study Eye (n=1,0,1,0,0,0)	-3.050 ( 99999 )	999999 ( 999999 )	-6.530 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 9: Study Eye (n=1,0,0,0,0,0)	-3.470 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 9: Non-Study Eye (n=1,0,1,0,0,0)	-3.100 ( 99999 )	999999 ( 999999 )	-9.130 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 12: Study Eye (n=1,0,0,0,0,0)	-3.640 ( 99999 )	999999 ( 9999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 12: Non-Study Eye (n=1,0,1,0,0,0)	-3.760 ( 99999 )	999999 ( 999999 )	-9.220 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 18: Study Eye (n=1,0,0,0,0,0)	-3.670 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 18: Non-Study Eye (n=1,0,1,0,0,0)	-3.830 ( 99999 )	999999 ( 99999 )	-11.700 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 24: Study Eye (n=1,0,0,0,0,0)	-3.740 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Change at Month 24: Non-Study Eye (n=1,0,0,0,0,0)	-4.120 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Fundus Autofluoroscence- Distance from Foveal Center (FC) to Nearest Border of Preserved Autofluoroscence

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End point title

Part 1: Change from Baseline in Fundus Autofluoroscence- Distance from Foveal Center (FC) to Nearest Border of Preserved Autofluoroscence ^[106]

End point description

Fundus Autofluoroscence was used to assess change in distance from foveal center (FC) to nearest border of preserved autofluoroscence. Here negative values indicate decline in total area of preserved autofluoroscence. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR). 99999 indicates that standard deviation was not evaluable as there was only 1 subject. 999999 indicates that data was not evaluable at given time point. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Month 1, 3, 6, 9, 12, 18 and 24

Notes
[106] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: mm^2
arithmetic mean (standard deviation)
Baseline: Study Eye (n=2,1,1,1,1,0)	2394.50 ( 665.387 )	-39.00 ( 99999 )	3018.00 ( 99999 )	361.00 ( 99999 )	2853.00 ( 99999 )	999999 ( 999999 )
Baseline: Non-Study Eye (n=2,1,1,1,1,1)	2609.00 ( 386.080 )	-24.00 ( 99999 )	3052.00 ( 99999 )	369.00 ( 99999 )	2816.00 ( 99999 )	4047.00 ( 99999 )
Change at Month 1: Study Eye (n=2,1,1,1,1,0)	-33.00 ( 5.657 )	-14.00 ( 99999 )	-52.00 ( 99999 )	-14.00 ( 99999 )	-5.00 ( 99999 )	999999 ( 999999 )
Change at Month 1: Non-Study Eye (n=2,1,1,1,1,1)	-255.50 ( 297.692 )	-19.00 ( 99999 )	-281.00 ( 99999 )	-18.00 ( 99999 )	-12.00 ( 99999 )	-3.00 ( 99999 )
Change at Month 3: Study Eye (n=2,1,1,1,1,0)	-87.00 ( 24.042 )	-16.00 ( 99999 )	-138.00 ( 99999 )	-89.00 ( 99999 )	-104.00 ( 99999 )	999999 ( 999999 )
Change at Month 3: Non-Study Eye (n=2,1,1,1,1,1)	-276.50 ( 324.562 )	-30.00 ( 99999 )	-375.00 ( 99999 )	-22.00 ( 99999 )	-93.00 ( 99999 )	-21.00 ( 99999 )
Change at Month 6: Study Eye (n=2,1,1,1,1,0)	-128.50 ( 54.447 )	-24.00 ( 99999 )	-179.00 ( 99999 )	-93.00 ( 99999 )	-122.00 ( 99999 )	999999 ( 999999 )
Change at Month 6: Non-Study Eye (n=2,1,1,1,1,1)	-297.00 ( 349.311 )	-41.00 ( 99999 )	-462.00 ( 99999 )	-36.00 ( 99999 )	-102.00 ( 99999 )	999999 ( 999999 )
Change at Month 9: Study Eye (n=2,1,1,1,1,0)	-140.00 ( 41.012 )	-35.00 ( 99999 )	-281.00 ( 99999 )	-94.00 ( 99999 )	-140.00 ( 99999 )	999999 ( 999999 )
Change at Month 9: Non-Study Eye (n=2,1,1,1,1,1)	-310.50 ( 333.047 )	-58.00 ( 99999 )	-413.00 ( 99999 )	-38.00 ( 99999 )	92.00 ( 99999 )	999999 ( 999999 )
Change at Month 12: Study Eye (n=2,0,1,1,1,0)	-1489.50 ( 1829.285 )	999999 ( 999999 )	-282.00 ( 99999 )	-101.00 ( 99999 )	-708.00 ( 99999 )	999999 ( 999999 )
Change at Month 12: Non-Study Eye (n=2,0,1,1,1,1)	-353.50 ( 318.905 )	999999 ( 999999 )	-422.00 ( 99999 )	-39.00 ( 99999 )	89.00 ( 99999 )	999999 ( 999999 )
Change at Month 18: Study Eye (n=2,1,1,1,1,0)	-1493.00 ( 1829.992 )	-55.00 ( 99999 )	-310.00 ( 99999 )	-123.00 ( 99999 )	-1278.00 ( 99999 )	999999 ( 999999 )
Change at Month 18: Non-Study Eye (n=2,1,1,1,1,0)	-358.00 ( 318.198 )	-86.00 ( 99999 )	-425.00 ( 99999 )	-11.00 ( 99999 )	65.00 ( 99999 )	999999 ( 999999 )
Change at Month 24: Study Eye (n=2,1,1,1,1,0)	-1501.00 ( 1820.093 )	-69.00 ( 99999 )	-226.00 ( 99999 )	-125.00 ( 99999 )	-1293.00 ( 99999 )	999999 ( 999999 )
Change at Month 24: Non-Study Eye (n=2,1,1,1,1,0)	-391.00 ( 301.227 )	-91.00 ( 99999 )	-2646.00 ( 99999 )	-13.00 ( 99999 )	62.00 ( 99999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Volume of 30-Degree Hill of Vision

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End point title

Part 1: Change from Baseline in Volume of 30-Degree Hill of Vision ^[107]

End point description

Visual field testing was performed to assess change in volume of 30-degree hill vision. Reliability Factor (RF)=number of false positive responses + number of false negative responses/number of false positive presentations + number of false negative presentations*100. If there are 0 responses, then RF value=0. RFpositive=number of false positive responses/number of false positive presentations*100. If RF≤ 20% measurement is considered reliable. If 20% < RF ≤ 25% and RFpositive ≤ 10% measurement is also considered reliable. Otherwise if 20% < RF ≤ 25% and RFpositive > 10%, or RF > 25%, measurement is not reliable. Only reliable measurements were included for analysis of this endpoint. Here negative values indicate decline in volume of 30-degree hill vision. Safety analysis set. 99999= standard deviation was not evaluable as there was only 1 subject. 999999=data was not evaluable at given time point. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Month 6, 12 and 24

Notes
[107] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: decibel
arithmetic mean (standard deviation)
Baseline: Study Eye (n=0,0,0,0,1,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	2.73 ( 99999 )	5.07 ( 99999 )
Baseline: Non-Study Eye (n=0,0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	5.17 ( 99999 )
Change at Month 6: Study Eye (n=0,0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	-2.14 ( 99999 )
Change at Month 6: Non-Study Eye (n=0,0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	-1.10 ( 99999 )
Change at Month 12: Study Eye (n=0,0,0,0,1,1),	999999 ( 999999 )	999999 ( 999999 )	9999999 ( 999999 )	999999 ( 999999 )	0.33 ( 999999 )	-2.80 ( 99999 )
Change at Month 12: Non-Study Eye (n=0,0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	-1.02 ( 99999 )
Change at Month 24: Study Eye (n=0,0,0,0,1,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	-1.89 ( 99999 )	-3.08 ( 99999 )
Change at Month 24: Non-Study Eye (n=0,0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	-2.11 ( 99999 )

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Volume of Full Field Hill of Vision

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End point title

Part 1: Change from Baseline in Volume of Full Field Hill of Vision ^[108]

End point description

Visual field testing was performed to assess change in volume of full field of hill vision. Reliability Factor (RF)=number of false positive responses + number of false negative responses/number of false positive presentations + number of false negative presentations*100. If there are 0 responses, then RF value=0. RFpositive=number of false positive responses/number of false positive presentations*100. If RF≤ 20% measurement is considered reliable. If 20% < RF ≤ 25% and RFpositive ≤ 10% measurement is also considered reliable. Otherwise if 20% < RF ≤ 25% and RFpositive > 10%, or RF > 25%, measurement is not reliable. Only reliable measurements were included for analysis of this endpoint. Here negative values indicate decline in volume of 30-degree hill vision. Safety analysis set. 99999= standard deviation was not evaluable as there was only 1 subject. 999999= data was not evaluable at given time point. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Month 6, 12, and 24

Notes
[108] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: decibel
arithmetic mean (standard deviation)
Baseline: Study Eye (n=0,0,0,0,1,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	15.77 ( 99999 )	18.31 ( 99999 )
Baseline: Non-Study Eye (n=0,0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	99999 ( 999999 )	23.41 ( 99999 )
Change at Month 6: Study Eye (n=0,0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	-0.86 ( 99999 )
Change at Month 6: Non-Study Eye (n=0,0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	-4.91 ( 99999 )
Change at Month 12: Study Eye (n=0,0,0,0,1,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	1.29 ( 99999 )	-2.98 ( 99999 )
Change at Month 12: Non-Study Eye (n=0,0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	-3.70 ( 99999 )
Change at Month 24: Study Eye (n=0,0,0,0,1,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	-6.28 ( 99999 )	-5.36 ( 99999 )
Change at Month 24: Non-Study Eye (n=0,0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	-7.87 ( 99999 )

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Contrast Sensitivity

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End point title

Part 1: Change from Baseline in Contrast Sensitivity ^[109]

End point description

Change in contrast sensitivity (CS) was assessed by Pelli-Robson chart which uses a single large letter size (20/60 optotype), with contrast varying across groups of letters. Chart uses letters (6 per line), arranged in groups whose contrast varies from high to low. Subjects read the letters, starting with the highest contrast, until they are unable to read two or three letters in a single group. Each group has three letters of the same contrast level, so there are three trials per contrast level. Subject is assigned a score based on the contrast of the last group in which two or three letters were correctly read. Score is a measure of the subject’s log contrast sensitivity ranging from 0-2.25, with 0 being no letters read, and 2.25 being all letters read. Total CS score = [(total # letters correct - 3) x 0.05]. Safety analysis set consist of all subjects who received study treatment (vitrectomy/AAV8-RPGR). n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Part 1: Month 3, 6, 12 and 24

Notes
[109] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 1, hence data was reported for Part 1 reporting arm groups only.

End point values	Part 1: BIIB112 Dose 1	Part 1: BIIB112 Dose 2	Part 1: BIIB112 Dose 3	Part 1: BIIB112 Dose 4	Part 1: BIIB112 Dose 5	Part 1: BIIB112 Dose 6
Number of subjects analysed	3	3	3	3	3	3
Units: Score on scale
arithmetic mean (standard deviation)
Baseline: Study Eye (n=3,3,3,3,3,3)	0.300 ( 0.1732 )	0.533 ( 0.2309 )	0.900 ( 0.1732 )	0.883 ( 0.3884 )	1.267 ( 0.0289 )	1.067 ( 0.6110 )
Baseline: Non-Study (n=3,3,3,3,3,3)	0.433 ( 0.2082 )	0.583 ( 0.2255 )	1.050 ( 0.2598 )	0.933 ( 0.4646 )	1.350 ( 0.1803 )	1.100 ( 0.3279 )
Change at Month 3: Study Eye (n=3,3,3,3,3,3)	0.167 ( 0.1528 )	0.183 ( 0.2566 )	0.150 ( 0.0866 )	0.133 ( 0.1155 )	-0.033 ( 0.4163 )	-0.167 ( 0.3014 )
Change at Month 3: Non-Study Eye (n=3,3,3,3,3,3)	0.000 ( 0.0000 )	0.017 ( 0.4010 )	0.050 ( 0.0500 )	0.050 ( 0.0500 )	0.100 ( 0.0000 )	0.000 ( 0.1000 )
Change at Month 6: Study Eye (n=3,3,3,3,3,3)	0.133 ( 0.2082 )	0.067 ( 0.2363 )	0.100 ( 0.1323 )	0.133 ( 0.0577 )	-0.183 ( 0.4072 )	0.117 ( 0.2021 )
Change at Month 6: Non-Study Eye (n=3,3,3,3,3,3)	0.000 ( 0.1732 )	0.033 ( 0.2255 )	0.083 ( 0.0764 )	0.050 ( 0.1000 )	-0.100 ( 0.0500 )	0.000 ( 0.0500 )
Change at Month 12: Study Eye (n=2,3,3,3,3,3)	0.100 ( 0.1414 )	0.133 ( 0.3512 )	-0.017 ( 0.1041 )	0.183 ( 0.0577 )	-0.167 ( 0.6788 )	-0.017 ( 0.3329 )
Change at Month 12: Non-Study Eye (n=2,3,3,3,3,3)	-0.100 ( 0.2828 )	0.067 ( 0.3512 )	0.000 ( 0.0000 )	0.000 ( 0.0500 )	-0.100 ( 0.1323 )	-0.050 ( 0.1323 )
Change at Month 24: Study Eye (n=3,3,3,3,3,3)	0.000 ( 0.2291 )	0.017 ( 0.5965 )	-0.100 ( 0.0000 )	0.217 ( 0.1893 )	-0.217 ( 0.5346 )	-0.117 ( 0.2466 )
Change at Month 24: Non-Study Eye (n=3,3,3,3,3,3)	-0.183 ( 0.1258 )	0.117 ( 0.3884 )	-0.100 ( 0.1732 )	0.017 ( 0.2021 )	-0.050 ( 0.1323 )	-0.050 ( 0.0500 )

No statistical analyses for this end point

Secondary: Part 2: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 out of the 16 Central Loci in Microperimetry

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End point title

Part 2: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 out of the 16 Central Loci in Microperimetry ^[110]

End point description

MAIA microperimetry assessment was measured in decibel (dB) using a 10-2 grid of 68 points. Each point was labelled as ‘< 0’, ‘0’ or a positive integer. The point labelled as ‘< 0’ is assigned a value of ‘-1’ by MAIA in the calculation. Improvement in Retinal Sensitivity in center grid was defined as an increase from baseline of 7 or more decibels in any 5 or more points out of the 16 central points. ITT analysis set included all subjects who were randomized, under the 3-arm randomization schedules. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6 and 9

Notes
[110] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	10	10
Units: percentage of study eyes
number (confidence interval 80%)
Month 1 (n=9,10,10)	22.2 (6.1 to 49.0)	30.0 (11.6 to 55.2)	40.0 (18.8 to 64.6)
Month 2 (n=9,10,10)	22.2 (6.1 to 49.0)	30.0 (11.6 to 55.2)	50.0 (26.7 to 73.3)
Month 3 (n=8,10,10)	12.5 (1.3 to 40.6)	30.0 (11.6 to 55.2)	60.0 (35.4 to 81.2)
Month 6 (n=9,9,8)	22.2 (6.1 to 49.0)	33.3 (12.9 to 59.9)	62.5 (34.5 to 85.3)
Month 9 (n=9,7,7)	22.2 (6.1 to 49.0)	28.6 (7.9 to 59.6)	42.9 (17.0 to 72.1)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 Out of the 68 Loci in Microperimetry

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End point title

Part 2: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 Out of the 68 Loci in Microperimetry ^[111]

End point description

MAIA microperimetry assessment was measured in decibel (dB) using a 10-2 grid of 68 points. Each point was labelled as ‘< 0’, ‘0’ or a positive integer. The point labelled as ‘< 0’ was assigned a value of ‘-1’ by MAIA in the calculation. Improvement in Retinal Sensitivity in whole grid was defined as an increase from baseline of 7 or more decibels in any 5 or more points of the grid as a whole (68 points). ITT analysis set included all subjects who were randomized, under the 3-arm randomization schedules. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9 and 12

Notes
[111] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	10	10
Units: percentage of study eyes
number (confidence interval 80%)
Month 1 (n=9,10,10)	33.3 (12.9 to 59.9)	60.0 (35.4 to 81.2)	40.0 (18.8 to 64.6)
Month 2 (n=9,10,10)	22.2 (6.1 to 49.0)	80.0 (55.0 to 94.5)	80.0 (55.0 to 94.5)
Month 3 (n=8,10,10)	25.0 (6.9 to 53.8)	80.0 (55.0 to 94.5)	70.0 (44.8 to 88.4)
Month 6 (n=9,9,8)	33.3 (12.9 to 59.9)	77.8 (51.0 to 93.9)	100.0 (75.0 to 100.0)
Month 9 (n=9,7,7)	33.3 (12.9 to 59.9)	85.7 (54.7 to 98.5)	71.4 (40.4 to 92.1)
Month 12 (n=9,8,8)	33.3 (12.9 to 59.9)	62.5 (34.5 to 85.3)	62.5 (34.5 to 85.3)

No statistical analyses for this end point

Secondary: Part 2: Change from Baseline in Mean Sensitivity of the 16 Central Loci

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End point title

Part 2: Change from Baseline in Mean Sensitivity of the 16 Central Loci ^[112]

End point description

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as ‘< 0’, ‘0’ or a positive integer. The point labelled as ‘< 0’ was assigned a value of ‘-1’ by MAIA in the calculation. Mean Sensitivity in center grid was defined as the mean in dB of the 16 points located in the center of the grid. Here negative values indicate a decline in retinal sensitivity. ITT analysis set included all subjects who were randomized, under the 3-arm randomization schedules. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Month 1, 2, 3, 6, 9 and 12

Notes
[112] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	10	10
Units: decibel
arithmetic mean (standard deviation)
Baseline: Study Eye (n=9,10,10)	6.78 ( 3.488 )	7.39 ( 5.207 )	7.38 ( 3.095 )
Baseline: Non-Study Eye (n=9,10,10)	9.56 ( 3.321 )	9.09 ( 5.003 )	8.98 ( 3.583 )
Change at Month 1: Study Eye (n=9,10,10)	1.53 ( 3.086 )	2.70 ( 3.731 )	0.10 ( 5.723 )
Change at Month 1: Non-Study Eye (n=9,10,10)	-0.26 ( 1.692 )	-0.76 ( 1.793 )	-0.08 ( 0.834 )
Change at Month 2: Study Eye (n=9,10,10)	1.62 ( 2.846 )	2.73 ( 4.360 )	1.55 ( 5.886 )
Change at Month 2: Non-Study Eye (n=9,10,10)	-0.34 ( 2.027 )	-0.44 ( 1.723 )	0.26 ( 1.118 )
Change at Month 3: Study Eye (n=8,10,10)	1.17 ( 2.760 )	2.77 ( 4.598 )	1.00 ( 6.862 )
Change at Month 3: Non-Study Eye (n=8,10,10)	-1.24 ( 1.253 )	0.07 ( 1.393 )	-0.24 ( 0.500 )
Change at Month 6: Study Eye (n=9,9,8)	0.72 ( 3.208 )	3.38 ( 4.770 )	3.74 ( 3.931 )
Change at Month 6: Non-Study Eye (n=9,9,8)	-0.69 ( 2.199 )	-0.35 ( 1.125 )	-0.66 ( 0.702 )
Change at Month 9: Study Eye (n=9,7,7)	0.65 ( 3.272 )	2.52 ( 4.619 )	2.54 ( 6.317 )
Change at Month 9: Non-Study Eye (n=9,8,7)	-1.01 ( 1.943 )	0.30 ( 1.654 )	-0.54 ( 0.636 )
Change at Month 12: Study Eye (n=9,8,8)	-0.11 ( 4.446 )	2.79 ( 4.663 )	1.16 ( 5.660 )
Change at Month 12: Non-Study Eye (n=9,9,8)	-2.23 ( 4.018 )	-0.44 ( 1.078 )	-1.04 ( 1.292 )

No statistical analyses for this end point

Secondary: Part 2: Change from Baseline in Mean Sensitivity of the 68 Central Loci

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End point title

Part 2: Change from Baseline in Mean Sensitivity of the 68 Central Loci ^[113]

End point description

MAIA microperimetry assessment was measured in decibel (dB) using a 10-2 grid of 68 points. Each point was labelled as ‘< 0’, ‘0’ or a positive integer. The point labelled as ‘< 0’ was assigned a value of ‘-1’ by MAIA in the calculation. Improvement in Retinal Sensitivity in whole grid was defined as an increase from baseline of 7 or more decibels in any 5 or more points of the grid as a whole (68 points). Here negative values indicate a decline in retinal sensitivity. ITT analysis set included all subjects who were randomized, under the 3-arm randomization schedules. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Month 1, 2, 3, 6, 9, and 12

Notes
[113] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	10	10
Units: decibel
arithmetic mean (standard deviation)
Baseline: Study Eye (n=9,10,10)	2.15 ( 2.182 )	2.46 ( 1.911 )	3.84 ( 2.138 )
Baseline: Non-Study Eye (n=9,10,10)	3.32 ( 2.539 )	3.34 ( 2.092 )	4.47 ( 2.331 )
Change at Month 1: Study Eye (n=9,10,10)	0.91 ( 1.389 )	1.60 ( 2.225 )	-0.07 ( 3.898 )
Change at Month 1: Non-Study Eye (n=9,10,10)	0.12 ( 1.214 )	-0.46 ( 1.044 )	-0.03 ( 0.850 )
Change at Month 2: Study Eye (n=9,10,10)	0.90 ( 0.972 )	2.34 ( 2.353 )	1.18 ( 3.367 )
Change at Month 2: Non-Study Eye (n=9,10,10)	0.30 ( 1.111 )	-0.23 ( 0.859 )	0.13 ( 0.668 )
Change at Month 3: Study Eye (n=8,10,10)	0.46 ( 1.064 )	2.64 ( 2.962 )	0.24 ( 3.962 )
Change at Month 3: Non-Study Eye (n=8,10,10)	-0.16 ( 0.743 )	-0.03 ( 0.516 )	-0.11 ( 0.619 )
Change at Month 6: Study Eye (n=9,9,8)	0.32 ( 1.301 )	3.15 ( 3.283 )	2.05 ( 3.007 )
Change at Month 6: Non-Study Eye (n=9,9,8)	-0.13 ( 1.283 )	-0.27 ( 0.527 )	-0.50 ( 0.632 )
Change at Month 9: Study Eye (n=9,7,7)	0.40 ( 1.456 )	2.80 ( 3.116 )	1.71 ( 3.605 )
Change at Month 9: Non- Study Eye (n=9,8,7)	-0.41 ( 1.150 )	-0.05 ( 0.790 )	0.09 ( 0.544 )
Change at Month 12: Study Eye (n=9,8,8)	0.11 ( 1.592 )	2.79 ( 3.045 )	0.89 ( 3.132 )
Change at Month 12: Non-Study Eye (n=9,9,8)	-0.84 ( 1.749 )	-0.28 ( 0.476 )	-0.35 ( 1.004 )

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in BCVA

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End point title

Part 2: Change From Baseline in BCVA ^[114]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. Here negative values indicate a decline in BCVA. ITT analysis set consist of all subjects that were randomised under the 3-arm randomisation schedules. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Month 1, 2, 3, 6, 9, and 12

Notes
[114] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	10	10
Units: letters
arithmetic mean (standard deviation)
Baseline: Study Eye (n=9,10,10)	68.78 ( 5.954 )	65.90 ( 10.104 )	68.20 ( 8.991 )
Baseline: Non-Study Eye (n=9,10,10)	72.89 ( 6.846 )	68.50 ( 9.675 )	68.80 ( 6.989 )
Change at Month 1: Study Eye (n=9,10,10)	0.44 ( 2.833 )	1.60 ( 6.450 )	0.60 ( 7.545 )
Change at Month 1: Non-Study Eye (n=9,10,10)	-0.89 ( 2.028 )	0.00 ( 4.110 )	3.80 ( 3.360 )
Change at Month 2: Study Eye (n=9,10,10)	0.22 ( 2.108 )	-1.00 ( 12.392 )	0.00 ( 8.957 )
Change at Month 2: Non-Study Eye (n=9,10,10)	-0.11 ( 1.269 )	0.60 ( 2.836 )	3.10 ( 2.644 )
Change at Month 3: Study Eye (n=8,10,10)	1.38 ( 2.615 )	0.10 ( 6.540 )	-0.30 ( 11.036 )
Change at Month 3: Non-Study Eye (n=8,10,10)	0.13 ( 2.642 )	1.10 ( 2.470 )	3.20 ( 2.860 )
Change at Month 6: Study Eye (n=9,9,8)	1.00 ( 2.000 )	2.44 ( 5.003 )	-0.38 ( 5.630 )
Change at Month 6: Non-Study Eye (n=9,9,8)	-1.56 ( 2.833 )	0.67 ( 1.581 )	1.00 ( 4.629 )
Change at Month 9: Study Eye (n=9,8,7)	0.44 ( 1.944 )	-2.50 ( 14.263 )	-0.57 ( 1.397 )
Change at Month 9: Non-Study Eye (n=9,8,7)	-1.78 ( 2.949 )	1.00 ( 2.000 )	1.71 ( 3.147 )
Change at Month 12: Study Eye (n=9,9,8)	0.22 ( 2.949 )	-4.00 ( 17.436 )	-0.75 ( 3.370 )
Change at Month 12: Non-Study Eye (n=9,9,7)	-4.11 ( 3.983 )	0.89 ( 3.100 )	2.14 ( 3.976 )

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in LLVA

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End point title

Part 2: Change From Baseline in LLVA ^[115]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. Here negative values indicate decline in LLVA. ITT analysis set included all subjects that were randomised under the 3-arm randomisation schedules. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Baseline, Month 1, 3, 6, 9, and 12

Notes
[115] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9 ^[116]	10 ^[117]	10 ^[118]
Units: letters
arithmetic mean (standard deviation)
Baseline: Study Eye (n=9,10,10)	50.22 ( 13.349 )	39.30 ( 22.246 )	47.90 ( 14.970 )
Baseline: Non-Study Eye (n=9,10,10)	54.78 ( 11.872 )	49.50 ( 19.127 )	51.60 ( 9.524 )
Change at Month 1: Study Eye (n=9,10,10)	0.56 ( 7.618 )	11.30 ( 16.918 )	-1.30 ( 18.397 )
Change at Month 1: Non-Study Eye (n=9,10,10)	0.22 ( 5.215 )	-3.00 ( 9.165 )	3.50 ( 4.882 )
Change at Month 3: Study Eye (n=8,10,10)	3.63 ( 7.230 )	8.10 ( 16.251 )	-3.50 ( 22.609 )
Change at Month 3: Non-Study Eye (n=8,10,10)	-0.63 ( 8.158 )	0.50 ( 3.749 )	1.20 ( 3.553 )
Change at Month 6: Study Eye (n=9,9,8)	1.22 ( 7.032 )	8.00 ( 18.581 )	3.25 ( 14.636 )
Change at Month 6: Non-Study Eye (n=9,9,8)	0.11 ( 6.274 )	-3.56 ( 8.472 )	2.13 ( 2.850 )
Change at Month 9: Study Eye (n=9,8,7)	-1.78 ( 7.225 )	8.38 ( 16.088 )	6.00 ( 12.356 )
Change at Month 9: Non-Study Eye (n=9,8,7)	-3.11 ( 7.491 )	-1.13 ( 6.749 )	4.00 ( 4.082 )
Change at Month 12: Study Eye (n=9,9,8)	-2.22 ( 7.412 )	5.11 ( 14.426 )	-0.63 ( 11.575 )
Change at Month 12: Non-Study Eye (n=9,9,8)	-4.44 ( 7.002 )	-3.56 ( 11.652 )	-1.50 ( 4.309 )

Notes
[116] - 'Number of Subjects Analyzed' signifies number of subjects analyzed in this endpoint.
[117] - 'Number of Subjects Analyzed' signifies number of subjects analyzed in this endpoint.
[118] - 'Number of Subjects Analyzed' signifies number of subjects analyzed in this endpoint.

No statistical analyses for this end point

Secondary: Part 2: Percentage of Eyes with a ≥15 Letter Increase From Baseline for BCVA

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End point title

Part 2: Percentage of Eyes with a ≥15 Letter Increase From Baseline for BCVA ^[119]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. ITT analysis set included all subjects that were randomised under the 3-arm randomisation schedules. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, and 12

Notes
[119] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	10	10
Units: percentage of eyes
number (confidence interval 80%)
Month 1: Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	10.0 (1.0 to 33.7)
Month 1: Non-Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	0.0 (0.0 to 20.6)
Month 2: Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	10.0 (1.0 to 33.7)
Month 2: Non-Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	0.0 (0.0 to 20.6)
Month 3: Study Eye (n=8,10,10)	0.0 (0.0 to 25.0)	0.0 (0.0 to 20.6)	10.0 (1.0 to 33.7)
Month 3: Non-Study Eye (n=8,10,10)	0.0 (0.0 to 25.0)	0.0 (0.0 to 20.6)	0.0 (0.0 to 20.6)
Month 6: Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)	0.0 (0.0 to 25.0)
Month 6: Non-Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)	0.0 (0.0 to 25.0)
Month 9: Study Eye (n=9,8,7)	0.0 (0.0 to 22.6)	0.0 (0.0 to 25.0)	0.0 (0.0 to 28.0)
Month 9: Non-Study Eye (n=9,8,7)	0.0 (0.0 to 22.6)	0.0 (0.0 to 25.0)	0.0 (0.0 to 28.0)
Month 12: Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)	0.0 (0.0 to 25.0)
Month 12: Non-Study Eye (n=9,9,7)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)	0.0 (0.0 to 28.0)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Eyes with a ≥15 Letter Increase From Baseline for LLVA

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End point title

Part 2: Percentage of Eyes with a ≥15 Letter Increase From Baseline for LLVA ^[120]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. ITT analysis set included all subjects that were randomised under the 3-arm randomisation schedules. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, and 12

Notes
[120] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	10	10
Units: percentage of eyes
number (confidence interval 80%)
Month 1: Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	40.0 (18.8 to 64.6)	20.0 (5.5 to 45.0)
Month 1: Non-Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	10.0 (1.0 to 33.7)
Month 3: Study Eye (n=8,10,10)	0.0 (0.0 to 25.0)	40.0 (18.8 to 64.6)	30.0 (11.6 to 55.2)
Month 3: Non-Study Eye (n=8,10,10)	0.0 (0.0 to 25.0)	0.0 (0.0 to 20.6)	0.0 (0.0 to 20.6)
Month 6: Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	33.3 (12.9 to 59.9)	12.5 (1.3 to 40.6)
Month 6: Non-Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)	0.0 (0.0 to 25.0)
Month 9: Study Eye (n=9,8,7)	0.0 (0.0 to 22.6)	25.0 (6.9 to 53.8)	28.6 (7.9 to 59.6)
Month 9: Non-Study Eye (n=9,8,7)	0.0 (0.0 to 22.6)	0.0 (0.0 to 25.0)	0.0 (0.0 to 28.0)
Month 12: Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	33.3 (12.9 to 59.9)	12.5 (1.3 to 40.6)
Month 12: Non-Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)	0.0 (0.0 to 25.0)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Eyes with a ≥10 Letter Increase From Baseline for BCVA

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End point title

Part 2: Percentage of Eyes with a ≥10 Letter Increase From Baseline for BCVA ^[121]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. ITT analysis set included all subjects that were randomised under the 3-arm randomisation schedules. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, and 12

Notes
[121] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	10	10
Units: percentage of eyes
number (confidence interval 80%)
Month 1: Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	10.0 (1.0 to 33.7)
Month 1: Non-Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	10.0 (1.0 to 33.7)
Month 2: Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	20.0 (5.5 to 45.0)
Month 2: Non-Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	0.0 (0.0 to 20.6)
Month 3: Study Eye (n=8,10,10)	0.0 (0.0 to 25.0)	0.0 (0.0 to 20.6)	10.0 (1.0 to 33.7)
Month 3: Non-Study Eye (n=8,10,10)	0.0 (0.0 to 25.0)	0.0 (0.0 to 20.6)	0.0 (0.0 to 20.6)
Month 6: Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)	12.5 (1.3 to 40.6)
Month 6: Non-Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)	0.0 (0.0 to 25.0)
Month 9: Study Eye (n=9,8,7)	0.0 (0.0 to 22.6)	0.0 (0.0 to 25.0)	0.0 (0.0 to 28.0)
Month 9: Non-Study Eye (n=9,8,7)	0.0 (0.0 to 22.6)	0.0 (0.0 to 25.0)	0.0 (0.0 to 28.0)
Month 12: Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	11.1 (1.2 to 36.8)	0.0 (0.0 to 25.0)
Month 12: Non-Study Eye (n=9,9,7)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)	0.0 (0.0 to 28.0)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Eyes with a ≥10 Letter Increase From Baseline for LLVA

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End point title

Part 2: Percentage of Eyes with a ≥10 Letter Increase From Baseline for LLVA ^[122]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. ITT analysis set included all subjects that were randomised under the 3-arm randomisation schedules. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, and 12

Notes
[122] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	10	10
Units: percentage of eyes
number (confidence interval 80%)
Month 1: Study Eye (n=9,10,10)	11.1 (1.2 to 36.8)	40.0 (18.8 to 64.6)	30.0 (11.6 to 55.2)
Month 1: Non-Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	0.0 (0.0 to 20.6)
Month 3: Study Eye (n=8,10,10)	25.0 (6.9 to 53.8)	40.0 (18.8 to 64.6)	30.0 (11.6 to 55.2)
Month 3: Non-Study Eye (n=8,10,10)	12.5 (1.3 to 40.6)	0.0 (0.0 to 20.6)	0.0 (0.0 to 20.6)
Month 6: Study Eye (n=9,9,8)	11.1 (1.2 to 36.8)	44.4 (21.0 to 69.9)	37.5 (14.7 to 65.5)
Month 6: Non-Study Eye (n=9,9,8)	11.1 (1.2 to 36.8)	11.1 (1.2 to 36.8)	0.0 (0.0 to 25.0)
Month 9: Study Eye (n=9,8,7)	11.1 (1.2 to 36.8)	37.5 (14.7 to 65.5)	28.6 (7.9 to 59.6)
Month 9: Non-Study Eye (n=9,8,7)	11.1 (1.2 to 36.8)	12.5 (1.3 to 40.6)	14.3 (1.5 to 45.3)
Month 12: Study Eye (n=9,9,8)	11.1 (1.2 to 36.8)	33.3 (12.9 to 59.9)	12.5 (1.3 to 40.6)
Month 12: Non-Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	11.1 (1.2 to 36.8)	0.0 (0.0 to 25.0)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Eyes with a ≥5 Letter Increase From Baseline for BCVA

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End point title

Part 2: Percentage of Eyes with a ≥5 Letter Increase From Baseline for BCVA ^[123]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. ITT analysis set included all subjects that were randomised under the 3-arm randomisation schedules. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, and 12

Notes
[123] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	10	10
Units: percentage of eyes
number (confidence interval 80%)
Month 1: Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	60.0 (35.4 to 81.2)	20.0 (5.5 to 45.0)
Month 1: Non-Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	10.0 (1.0 to 33.7)	40.0 (18.8 to 64.6)
Month 2: Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	60.0 (35.4 to 81.2)	30.0 (11.6 to 55.2)
Month 2: Non-Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)	30.0 (11.6 to 55.2)
Month 3: Study Eye (n=8,10,10)	12.5 (1.3 to 40.6)	20.0 (5.5 to 45.0)	30.0 (11.6 to 55.2)
Month 3: Non-Study Eye (n=8,10,10)	0.0 (0.0 to 25.0)	0.0 (0.0 to 20.6)	20.0 (5.5 to 45.0)
Month 6: Study Eye (n=9,9,8)	11.1 (1.2 to 36.8)	44.4 (21.0 to 69.9)	12.5 (1.3 to 40.6)
Month 6: Non-Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)	25.0 (6.9 to 53.8)
Month 9: Study Eye (n=9,8,7)	0.0 (0.0 to 22.6)	37.5 (14.7 to 65.5)	0.0 (0.0 to 28.0)
Month 9: Non-Study Eye (n=9,8,7)	0.0 (0.0 to 22.6)	0.0 (0.0 to 25.0)	42.9 (17.0 to 72.1)
Month 12: Study Eye (n=9,9,8)	0.0 (0.0 to 22.6)	22.2 (6.1 to 49.0)	0.0 (0.0 to 25.0)
Month 12: Non-Study Eye (n=9,9,7)	0.0 (0.0 to 22.6)	11.1 (1.2 to 36.8)	28.6 (7.9 to 59.6)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Eyes with a ≥5 Letter Increase From Baseline for LLVA

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End point title

Part 2: Percentage of Eyes with a ≥5 Letter Increase From Baseline for LLVA ^[124]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. ITT analysis set included all subjects that were randomised under the 3-arm randomisation schedules. n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, and 12

Notes
[124] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9 ^[125]	10 ^[126]	10 ^[127]
Units: percentage of eyes
number (confidence interval 80%)
Month 1: Study Eye (n=9,10,10)	22.2 (6.1 to 49.0)	60.0 (35.4 to 81.2)	40.0 (18.8 to 64.6)
Month 1: Non-Study Eye (n=9,10,10)	22.2 (6.1 to 49.0)	30.0 (11.6 to 55.2)	30.0 (11.6 to 55.2)
Month 3: Study Eye (n=8,10,10)	37.5 (14.7 to 65.5)	50.0 (26.7 to 73.3)	30.0 (11.6 to 55.2)
Month 3: Non-Study Eye (n=8,10,10)	25.0 (6.9 to 53.8)	20.0 (5.5 to 45.0)	10.0 (1.0 to 33.7)
Month 6: Study Eye (n=9,9,8)	44.4 (21.0 to 69.9)	66.7 (40.1 to 87.1)	50.0 (24.0 to 76.0)
Month 6: Non-Study Eye (n=9,9,8)	22.2 (6.1 to 49.0)	11.1 (1.2 to 36.8)	25.0 (6.9 to 53.8)
Month 9: Study Eye (n=9,8,7)	22.2 (6.1 to 49.0)	62.5 (34.5 to 85.3)	57.1 (27.9 to 83.0)
Month 9: Non-Study Eye (n=9,8,7)	11.1 (1.2 to 36.8)	12.5 (1.3 to 40.6)	42.9 (17.0 to 72.1)
Month 12: Study Eye (n=9,9,8)	22.2 (6.1 to 49.0)	44.4 (21.0 to 69.9)	12.5 (1.3 to 40.6)
Month 12: Non-Study Eye (n=9,9,8)	11.1 (1.2 to 36.8)	22.2 (6.1 to 49.0)	0.0 (0.0 to 25.0)

Notes
[125] - 'Number of Subjects Analyzed' signifies number of subjects analyzed in this endpoint.
[126] - 'Number of Subjects Analyzed' signifies number of subjects analyzed in this endpoint.
[127] - 'Number of Subjects Analyzed' signifies number of subjects analyzed in this endpoint.

No statistical analyses for this end point

Secondary: Part 2: Percentage of Eyes with a ≥15 Letters Loss From Baseline for BCVA

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End point title

Part 2: Percentage of Eyes with a ≥15 Letters Loss From Baseline for BCVA ^[128]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. Safety analysis set consist of all subjects who received study treatment (vitrectomy/AAV8-RPGR). n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, and 12

Notes
[128] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	11	12
Units: percentage of eyes
number (confidence interval 80%)
Month 1: Study Eye (n=9,11,12)	0.0 (0.0 to 22.6)	0.0 (0.0 to 18.9)	8.3 (0.9 to 28.7)
Month 1: Non-Study Eye (n=9,11,12)	0.0 (0.0 to 22.6)	0.0 (0.0 to 18.9)	0.0 (0.0 to 17.5)
Month 2: Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	10.0 (1.0 to 33.7)	0.0 (0.0 to 20.6)
Month 2: Non- Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	0.0 (0.0 to 20.6)
Month 3: Study Eye (n=8,11,12)	0.0 (0.0 to 25.0)	0.0 (0.0 to 18.9)	8.3 (0.9 to 28.7)
Month 3: Non- Study Eye (n=8,11,12)	0.0 (0.0 to 25.0)	0.0 (0.0 to 18.9)	0.0 (0.0 to 17.5)
Month 6: Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	0.0 (0.0 to 20.6)
Month 6: Non- Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	0.0 (0.0 to 20.6)	0.0 (0.0 to 20.6)
Month 9: Study Eye (n=9,9,9)	0.0 (0.0 to 22.6)	11.1 (1.2 to 36.8)	11.1 (1.2 to 36.8)
Month 9: Non- Study Eye (n=9,9,9)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)
Month 12: Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	10.0 (1.0 to 33.7)	0.0 (0.0 to 20.6)
Month 12: Non- Study Eye (n=9,10,9)	0.0 (0.0 to 222.6)	0.0 (0.0 to 20.6)	0.0 (0.0 to 22.6)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Eyes with a ≥15 Letters Loss From Baseline for LLVA

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End point title

Part 2: Percentage of Eyes with a ≥15 Letters Loss From Baseline for LLVA ^[129]

End point description

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the subject. Safety analysis set included all subjects who received study treatment (vitrectomy/AAV8-RPGR). n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 3, 6, 9, and 12

Notes
[129] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	11	12
Units: percentage of eyes
number (confidence interval 80%)
Month 1: Study Eye (n=9,11,12)	0.0 (0.0 to 22.6)	0.0 (0.0 to 18.9)	33.3 (15.4 to 55.9)
Month 1: Non-Study Eye (n=9,11,12)	0.0 (0.0 to 22.6)	18.2 (4.9 to 41.5)	0.0 (0.0 to 17.5)
Month 3: Study Eye (n=8,11,12)	0.0 (0.0 to 25.0)	9.1 (1.0 to 31.0)	33.3 (15.4 to 55.9)
Month 3: Non-Study Eye (n=8,11,12)	0.0 (0.0 to 25.0)	0.0 (0.0 to 18.9)	0.0 (0.0 to 17.5)
Month 6: Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	20.0 (5.5 to 45.0)	20.0 (5.5 to 45.0)
Month 6: Non-Study Eye(n=9,10,10)	0.0 (0.0 to 22.6)	10.0 (1.0 to 33.7)	0.0 (0.0 to 20.6)
Month 9: Study Eye (n=9,9,9)	0.0 (0.0 to 22.6)	11.1 (1.2 to 36.8)	11.1 (1.2 to 36.8)
Month 9: Non-Study Eye (n=9,9,9)	11.1 (1.2 to 36.8)	0.0 (0.0 to 22.6)	0.0 (0.0 to 22.6)
Month 12: Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	10.0 (1.0 to 33.7)	20.0 (5.5 to 45.0)
Month 12: Non-Study Eye (n=9,10,10)	0.0 (0.0 to 22.6)	10.0 (1.0 to 33.7)	0.0 (0.0 to 20.6)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Eyes with a ≥10 Letters Loss From Baseline for BCVA

Top of page

End point title

Part 2: Percentage of Eyes with a ≥10 Letters Loss From Baseline for BCVA ^[130]

End point description

BCVA was assessed using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was to be reported as number of letters read correctly by the subject. An increase in the number of letters read correctly means that vision has improved. Safety analysis set consist of all subjects who received study treatment (vitrectomy/AAV8-RPGR). n=number of subjects analysed at specific timepoint.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, and 12

Notes
[130] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was for Part 2, hence data was reported for Part 2 reporting arm groups only.

End point values	Part 2: Untreated Group	Part 2: BIIB112 Low Dose	Part 2: BIIB112 High Dose
Number of subjects analysed	9	11	12
Units: percentage of eyes
arithmetic mean (confidence interval 80%)
Month 1: Study Eye (n=9,11,12)	0.0 (0.0 to 22.6)	9.1 (1.0 to 31.0)	8.3 (0.9 to 28.7)
Month 1: Non-Study Eye (n=9,11,12)	0.0 (0.0 to 22.6)	0.0 (0.0 to 18.9)	0.0 (0.0 to 17.5)
Month 2: Study Eye (n=9,10,10)

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Clinical trials

Clinical Trial Results: A Dose Escalation (Phase 1), and Dose Expansion (Phase 2/3) Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using an Adeno-Associated Viral Vector (AAV8) Encoding Retinitis Pigmentosa GTPase Regulator (RPGR)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part 1: Number of Subjects with Dose-Limiting Toxicities (DLTs)

Primary: Part 1: Number of Subjects with Dose-Limiting Toxicities (DLTs)

Primary: Part 1: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

Primary: Part 1: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

Primary: Part 2: Percentage of Study Eyes with ≥7 Decibels (dB) Improvement from Baseline at ≥5 of the 16 Central Loci of the 10-2 Grid Assessed by Macular Integrity Assessment (MAIA) Microperimetry

Primary: Part 2: Percentage of Study Eyes with ≥7 Decibels (dB) Improvement from Baseline at ≥5 of the 16 Central Loci of the 10-2 Grid Assessed by Macular Integrity Assessment (MAIA) Microperimetry

Primary: Part 2: Number of Subjects with TEAEs

Primary: Part 2: Number of Subjects with TEAEs

Secondary: Part 1: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 out of the 16 Central Loci in Microperimetry

Secondary: Part 1: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 out of the 16 Central Loci in Microperimetry

Secondary: Part 1: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 Out of the 68 Loci in Microperimetry

Secondary: Part 1: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 Out of the 68 Loci in Microperimetry

Secondary: Part 1: Change from Baseline in Mean Sensitivity of the 16 Central Loci

Secondary: Part 1: Change from Baseline in Mean Sensitivity of the 16 Central Loci

Secondary: Part 1: Change from Baseline in Mean Sensitivity of the 68 Central Loci

Secondary: Part 1: Change from Baseline in Mean Sensitivity of the 68 Central Loci

Secondary: Part 1: Change from Baseline in Best Corrected Visual Acuity (BCVA) Score

Secondary: Part 1: Change from Baseline in Best Corrected Visual Acuity (BCVA) Score

Secondary: Part 1: Change from Baseline in Low Luminance Visual Acuity (LLVA) Score

Secondary: Part 1: Change from Baseline in Low Luminance Visual Acuity (LLVA) Score

Secondary: Part 1: Percentage of Eyes with a ≥15 Letters Increase from Baseline for BCVA

Secondary: Part 1: Percentage of Eyes with a ≥15 Letters Increase from Baseline for BCVA

Secondary: Part 1: Percentage of Eyes with a ≥15 Letters Increase from Baseline for LLVA

Secondary: Part 1: Percentage of Eyes with a ≥15 Letters Increase from Baseline for LLVA

Secondary: Part 1: Percentage of Eyes with a ≥10 Letters Increase from Baseline for BCVA

Secondary: Part 1: Percentage of Eyes with a ≥10 Letters Increase from Baseline for BCVA

Secondary: Part 1: Percentage of Eyes with a ≥10 Letters Increase from Baseline for LLVA

Secondary: Part 1: Percentage of Eyes with a ≥10 Letters Increase from Baseline for LLVA

Secondary: Part 1: Percentage of Eyes with a ≥5 Letters Increase from Baseline for BCVA

Secondary: Part 1: Percentage of Eyes with a ≥5 Letters Increase from Baseline for BCVA

Secondary: Part 1: Percentage of Eyes with a ≥5 Letters Increase from Baseline for LLVA

Secondary: Part 1: Percentage of Eyes with a ≥5 Letters Increase from Baseline for LLVA

Secondary: Part 1: Percentage of Eyes with a ≥15 Letters Loss from Baseline for BCVA

Secondary: Part 1: Percentage of Eyes with a ≥15 Letters Loss from Baseline for BCVA

Secondary: Part 1: Percentage of Eyes with a ≥15 Letters Loss from Baseline for LLVA

Secondary: Part 1: Percentage of Eyes with a ≥15 Letters Loss from Baseline for LLVA

Secondary: Part 1: Percentage of Eyes with a ≥10 Letters Loss from Baseline for BCVA

Secondary: Part 1: Percentage of Eyes with a ≥10 Letters Loss from Baseline for BCVA

Secondary: Part 1: Percentage of Eyes with a ≥10 Letters Loss from Baseline for LLVA

Secondary: Part 1: Percentage of Eyes with a ≥10 Letters Loss from Baseline for LLVA

Secondary: Part 1: Percentage of Eyes with a ≥5 Letters Loss from Baseline for BCVA

Secondary: Part 1: Percentage of Eyes with a ≥5 Letters Loss from Baseline for BCVA

Secondary: Part 1: Percentage of Eyes with a ≥5 Letters Loss from Baseline for LLVA

Secondary: Part 1: Percentage of Eyes with a ≥5 Letters Loss from Baseline for LLVA

Secondary: Part 1: Percentage of Eyes with Change from Baseline > -5 Letters for BCVA

Secondary: Part 1: Percentage of Eyes with Change from Baseline > -5 Letters for BCVA

Secondary: Part 1: Percentage of Eyes with Change from Baseline > -5 Letters for LLVA

Secondary: Part 1: Percentage of Eyes with Change from Baseline > -5 Letters for LLVA

Secondary: Part 1: Change from Baseline in Central Ellipsoid Area

Secondary: Part 1: Change from Baseline in Central Ellipsoid Area

Secondary: Part 1: Change from Baseline in Central Horizontal Ellipsoid Width

Secondary: Part 1: Change from Baseline in Central Horizontal Ellipsoid Width

Secondary: Part 1: Change from Baseline in Fundus Autofluoroscence- Total Area of Preserved Autofluoroscence

Secondary: Part 1: Change from Baseline in Fundus Autofluoroscence- Total Area of Preserved Autofluoroscence

Secondary: Part 1: Change from Baseline in Fundus Autofluoroscence- Distance from Foveal Center (FC) to Nearest Border of Preserved Autofluoroscence

Secondary: Part 1: Change from Baseline in Fundus Autofluoroscence- Distance from Foveal Center (FC) to Nearest Border of Preserved Autofluoroscence

Secondary: Part 1: Change from Baseline in Volume of 30-Degree Hill of Vision

Secondary: Part 1: Change from Baseline in Volume of 30-Degree Hill of Vision

Secondary: Part 1: Change from Baseline in Volume of Full Field Hill of Vision

Secondary: Part 1: Change from Baseline in Volume of Full Field Hill of Vision

Secondary: Part 1: Change from Baseline in Contrast Sensitivity

Secondary: Part 1: Change from Baseline in Contrast Sensitivity

Secondary: Part 2: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 out of the 16 Central Loci in Microperimetry

Secondary: Part 2: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 out of the 16 Central Loci in Microperimetry

Secondary: Part 2: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 Out of the 68 Loci in Microperimetry

Secondary: Part 2: Percentage of Study Eyes with ≥7 dB Improvement from Baseline at ≥5 Out of the 68 Loci in Microperimetry

Secondary: Part 2: Change from Baseline in Mean Sensitivity of the 16 Central Loci

Secondary: Part 2: Change from Baseline in Mean Sensitivity of the 16 Central Loci

Secondary: Part 2: Change from Baseline in Mean Sensitivity of the 68 Central Loci

Secondary: Part 2: Change from Baseline in Mean Sensitivity of the 68 Central Loci

Clinical Trial Results:
A Dose Escalation (Phase 1), and Dose Expansion (Phase 2/3) Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using an Adeno-Associated Viral Vector (AAV8) Encoding Retinitis Pigmentosa GTPase Regulator (RPGR)