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Clinical Trial Results:
Single and Repeat Dose Study of the Safety and Efficacy of AGN-150998 in Patients with Exudative Age-related Macular Degeneration

Summary
EudraCT number	2011-002526-43
Trial protocol	DE AT IT
Global end of trial date	09 Apr 2014

Results information
Results version number	v1(current)
This version publication date	08 Apr 2016
First version publication date	08 Apr 2016
Other versions

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

150998-001

ISRCTN number

US NCT number

NCT01397409

WHO universal trial number (UTN)

Sponsor organisation name

Allergan, Inc

Sponsor organisation address

2525 Dupont Drive, Irvine, United States, 92612

Public contact

Medical Director, Allergan, +1 714-246-4500, clinicaltrials@allergan.com

Scientific contact

Medical Director, Allergan, +1 714-246-4500, clinicaltrials@allergan.com

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

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?

Analysis stage

Final

Date of interim/final analysis

17 Dec 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

31 Mar 2014

Global end of trial reached?

Yes

Global end of trial date

09 Apr 2014

Was the trial ended prematurely?

Main objective of the trial

This study was conducted in 3 stages. Stage 1 was an open-label, dose-escalation assessment of the safety of AGN-150998 administered as a single intravitreal injection to patients with advanced exudative Age-related Macular Degeneration (AMD). Stage 2 and Stage 3 were randomized, double-masked, comparisons of the safety and treatment effects on retinal edema and best-corrected visual acuity (BCVA) of AGN-150998 and ranibizumab in treatment-naive patients with exudative AMD. Study medication was administered as needed in Stage 2 and with a fixed-dosing schedule in Stage 3. The study objectives were (1) to identify the highest tolerated dose of AGN-150998, (2) to assess the safety and duration of treatment effects on retinal edema and BCVA, and (3) to characterize the systemic pharmacokinetic profile of AGN-150998.

Protection of trial subjects

All participants were required to read an sign an informed consent form.

Background therapy

Evidence for comparator

Actual start date of recruitment

29 Sep 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 167

Country: Number of subjects enrolled

France: 19

Country: Number of subjects enrolled

Israel: 25

Country: Number of subjects enrolled

Italy: 9

Country: Number of subjects enrolled

Germany: 6

Country: Number of subjects enrolled

Australia: 23

Country: Number of subjects enrolled

Switzerland: 12

Country: Number of subjects enrolled

Austria: 10

Worldwide total number of subjects

271

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

201

85 years and over

Subject disposition

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Recruitment details

Participants were enrolled in 43 study centers in 8 countries: Austria, Australia, France, Germany, Israel, Italy, Switzerland and the United States from 29 September 2011 to 09 April 2014.

Screening details

Patients with Age-related Macular Degeneration enrolled in the Stage 1 open label dose escalation study starting at a 1.0 mg dose. In Stage 2, patients were randomized in a 1:1:1 ratio to ranibizumab, 3.0 mg abicipar or 4.2 mg abicipar. In Stage 3, patients were randomized in a 3:3:2 ratio of 1.0 mg abicipar, 2.0 mg abicipar or 0.5 mg ranibizumab.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer

Are arms mutually exclusive

Yes

Stage 1: AGN-150998 4.2 mg

Arm description

Stage 1: AGN-150998 4.2 mg given as a single intravitreal injection.

Arm type

Experimental

Investigational medicinal product name

AGN-150998

Investigational medicinal product code

Other name

abicipar

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Single intravitreal injection

Stage 1: AGN-150998 3.0 mg

Arm description

Stage 1: AGN-150998 3.0 mg given as a single intravitreal injection.

Arm type

Experimental

Investigational medicinal product name

AGN-150998

Investigational medicinal product code

Other name

abicipar

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Single intravitreal injection

Stage 1: AGN-150998 2.0 mg

Arm description

Stage 1: AGN-150998 2.0 mg given as a single intravitreal injection

Arm type

Experimental

Investigational medicinal product name

AGN-150998

Investigational medicinal product code

Other name

abicipar

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Single intravitreal injection

Stage 1: AGN-150998 1.0 mg

Arm description

Stage 1: AGN-150998 1.0 mg given as a single intravitreal injection.

Arm type

Experimental

Investigational medicinal product name

AGN-150998

Investigational medicinal product code

Other name

abicipar

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Single intravitreal injection

Stage 2: AGN-150998 4.2 mg

Arm description

Stage 2: AGN-150998 4.2 mg (highest tolerated dose from Stage 1) given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.

Arm type

Experimental

Investigational medicinal product name

AGN-150998

Investigational medicinal product code

Other name

abicipar

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Single intravitreal injection

Stage 2: AGN-150998 3.0 mg

Arm description

Stage 2: AGN-150998 3.0 mg (one dose below highest tolerated dose from Stage 1) given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.

Arm type

Experimental

Investigational medicinal product name

AGN-150998

Investigational medicinal product code

Other name

abicipar

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Single intravitreal injection

Stage 2: Ranibizumab 0.5 mg

Arm description

Stage 2: ranibizumab 0.5 mg given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.

Arm type

Active comparator

Investigational medicinal product name

ranibizumab

Investigational medicinal product code

Other name

Lucentis®

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Single intavitreal injection

Stage 3: AGN-150998 2.0 mg

Arm description

Stage 3: AGN-150998 2.0 mg given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16.

Arm type

Experimental

Investigational medicinal product name

AGN-150998

Investigational medicinal product code

Other name

abicipar

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Single intravitreal injection

Stage 3: AGN-150998 1.0 mg

Arm description

Stage 3: AGN-150998 1.0 mg given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16.

Arm type

Experimental

Investigational medicinal product name

AGN-150998

Investigational medicinal product code

Other name

abicipar

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Single intravitreal injection

Stage 3: Ranibizumab 0.5 mg

Arm description

Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks

Arm type

Active comparator

Investigational medicinal product name

ranibizumab

Investigational medicinal product code

Other name

Lucentis®

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Single intavitreal injection

Number of subjects in period 1	Stage 1: AGN-150998 4.2 mg	Stage 1: AGN-150998 3.0 mg	Stage 1: AGN-150998 2.0 mg	Stage 1: AGN-150998 1.0 mg	Stage 2: AGN-150998 4.2 mg	Stage 2: AGN-150998 3.0 mg	Stage 2: Ranibizumab 0.5 mg	Stage 3: AGN-150998 2.0 mg	Stage 3: AGN-150998 1.0 mg	Stage 3: Ranibizumab 0.5 mg
Started	9	6	6	3	67	58	58	23	25	16
Completed	9	6	6	3	59	54	58	21	25	16
Not completed	0	0	0	0	8	4	0	2	0	0
Adverse event, non-fatal	-	-	-	-	6	3	-	1	-	-
Personal Reasons	-	-	-	-	1	-	-	-	-	-
Other Miscellaneous Reasons	-	-	-	-	1	1	-	1	-	-

Baseline characteristics

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Reporting group title

Stage 1: AGN-150998 4.2 mg

Reporting group description

Stage 1: AGN-150998 4.2 mg given as a single intravitreal injection.

Reporting group title

Stage 1: AGN-150998 3.0 mg

Reporting group description

Stage 1: AGN-150998 3.0 mg given as a single intravitreal injection.

Reporting group title

Stage 1: AGN-150998 2.0 mg

Reporting group description

Stage 1: AGN-150998 2.0 mg given as a single intravitreal injection

Reporting group title

Stage 1: AGN-150998 1.0 mg

Reporting group description

Stage 1: AGN-150998 1.0 mg given as a single intravitreal injection.

Reporting group title

Stage 2: AGN-150998 4.2 mg

Reporting group description

Stage 2: AGN-150998 4.2 mg (highest tolerated dose from Stage 1) given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.

Reporting group title

Stage 2: AGN-150998 3.0 mg

Reporting group description

Stage 2: AGN-150998 3.0 mg (one dose below highest tolerated dose from Stage 1) given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.

Reporting group title

Stage 2: Ranibizumab 0.5 mg

Reporting group description

Stage 2: ranibizumab 0.5 mg given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.

Reporting group title

Stage 3: AGN-150998 2.0 mg

Reporting group description

Stage 3: AGN-150998 2.0 mg given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16.

Reporting group title

Stage 3: AGN-150998 1.0 mg

Reporting group description

Stage 3: AGN-150998 1.0 mg given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16.

Reporting group title

Stage 3: Ranibizumab 0.5 mg

Reporting group description

Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks

Reporting group values	Stage 1: AGN-150998 4.2 mg	Stage 1: AGN-150998 3.0 mg	Stage 1: AGN-150998 2.0 mg	Stage 1: AGN-150998 1.0 mg	Stage 2: AGN-150998 4.2 mg	Stage 2: AGN-150998 3.0 mg	Stage 2: Ranibizumab 0.5 mg	Stage 3: AGN-150998 2.0 mg	Stage 3: AGN-150998 1.0 mg	Stage 3: Ranibizumab 0.5 mg	Total
Number of subjects	9	6	6	3	67	58	58	23	25	16	271
Age categorical
Units: Subjects
Adults 18-64 years	0	1	0	1	3	3	5	0	6	2	21
Adults 65-84 years	9	5	6	2	64	55	53	23	19	14	250
Adults ≥85 years	0	0	0	0	0	0	0	0	0	0	0
Age Continuous \|
Units: years
arithmetic mean (full range (min-max))	82.3 (68 to 89)	75.3 (62 to 86)	79.3 (72 to 91)	67.7 (64 to 71)	80.4 (58 to 95)	78.6 (63 to 94)	78.5 (59 to 92)	77.9 (67 to 89)	75.5 (54 to 91)	76.5 (53 to 86)	-
Gender, Male/Female
Units: Participants
Female	5	2	4	2	34	35	38	13	18	8	159
Male	4	4	2	1	33	23	20	10	7	8	112

Subject analysis set title

All Stage 1 Participants

Subject analysis set type

Safety analysis

Subject analysis set description

Stage 1 Al lParticipants

Subject analysis sets values	All Stage 1 Participants
Number of subjects	24
Age categorical
Units: Subjects
Adults 18-64 years	0
Adults 65-84 years	0
Adults ≥85 years	0
Age Continuous \|
Units: years
arithmetic mean (full range (min-max))	0 (0 to 0)
Gender, Male/Female
Units: Participants
Female	0
Male	0

End points

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Reporting group title

Stage 1: AGN-150998 4.2 mg

Reporting group description

Stage 1: AGN-150998 4.2 mg given as a single intravitreal injection.

Reporting group title

Stage 1: AGN-150998 3.0 mg

Reporting group description

Stage 1: AGN-150998 3.0 mg given as a single intravitreal injection.

Reporting group title

Stage 1: AGN-150998 2.0 mg

Reporting group description

Stage 1: AGN-150998 2.0 mg given as a single intravitreal injection

Reporting group title

Stage 1: AGN-150998 1.0 mg

Reporting group description

Stage 1: AGN-150998 1.0 mg given as a single intravitreal injection.

Reporting group title

Stage 2: AGN-150998 4.2 mg

Reporting group description

Stage 2: AGN-150998 4.2 mg (highest tolerated dose from Stage 1) given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.

Reporting group title

Stage 2: AGN-150998 3.0 mg

Reporting group description

Stage 2: AGN-150998 3.0 mg (one dose below highest tolerated dose from Stage 1) given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.

Reporting group title

Stage 2: Ranibizumab 0.5 mg

Reporting group description

Stage 2: ranibizumab 0.5 mg given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.

Reporting group title

Stage 3: AGN-150998 2.0 mg

Reporting group description

Stage 3: AGN-150998 2.0 mg given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16.

Reporting group title

Stage 3: AGN-150998 1.0 mg

Reporting group description

Stage 3: AGN-150998 1.0 mg given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16.

Reporting group title

Stage 3: Ranibizumab 0.5 mg

Reporting group description

Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks

Subject analysis set title

All Stage 1 Participants

Subject analysis set type

Safety analysis

Subject analysis set description

Stage 1 Al lParticipants

Primary: Highest Tolerated Dose (HTD) of AGN-150998

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End point title

Highest Tolerated Dose (HTD) of AGN-150998 ^[1]

End point description

Stage 1 evaluated the safety of a single intravitreal injection of AGN-150998 with doses ranging from 1.0 to 4.2 mg.

End point type

Primary

End point timeframe

24 Weeks

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: No Statistical Analysis is reported for this outcome measure.

End point values	All Stage 1 Participants
Number of subjects analysed	24
Units: mg
number (not applicable)	4.2

No statistical analyses for this end point

Primary: Stage 1: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

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End point title

Stage 1: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye ^[2] ^[3]

End point description

CRT was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from Baseline indicated improvement.

End point type

Primary

End point timeframe

Baseline, Week 4

Notes
[2] - 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: No Statistical Analysis is reported for this outcome measure.
[3] - 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: Not all arms in the baseline period are applicable to this outcome measure.

End point values	Stage 1: AGN-150998 4.2 mg	Stage 1: AGN-150998 3.0 mg	Stage 1: AGN-150998 2.0 mg	Stage 1: AGN-150998 1.0 mg
Number of subjects analysed	9	6	6	3
Units: microns
arithmetic mean (standard deviation)
Baseline	527.6 ± 126.79	540.3 ± 284.34	500.3 ± 155.65	564.3 ± 115.68
Change from Baseline at Week 4 (n=9,6,6,2)	-185.4 ± 161.23	-239.5 ± 234.03	-212.3 ± 182.94	-113.5 ± 135.06

No statistical analyses for this end point

Primary: Stage 2: Time between Baseline Treatment and Recurrence of Active Disease

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End point title

Stage 2: Time between Baseline Treatment and Recurrence of Active Disease ^[4] ^[5]

End point description

Recurrence of Active Disease was based on Best Corrected Visual Acuity (BCVA), Central Retinal Thickness (CRT) values as evaluated by the Central Reading Center (CRC) and the investigator assessments of haemorrhage.

End point type

Primary

End point timeframe

Baseline, Week 16

Notes
[4] - 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: No Statistical Analysis is reported for this outcome measure.
[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: Not all arms in the baseline period are applicable to this outcome measure.

End point values	Stage 2: AGN-150998 4.2 mg	Stage 2: AGN-150998 3.0 mg	Stage 2: Ranibizumab 0.5 mg
Number of subjects analysed	65	57	57
Units: days
median (inter-quartile range (Q1-Q3))	59 (43 to 109)	57 (43 to 86)	57 (43 to 85)

No statistical analyses for this end point

Primary: Stage 3: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye

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End point title

Stage 3: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye ^[6] ^[7]

End point description

BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.

End point type

Primary

End point timeframe

Baseline, Week 16

Notes
[6] - 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: No Statistical Analysis is reported for this outcome measure.
[7] - 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: Not all arms in the baseline period are applicable to this outcome measure.

End point values	Stage 3: AGN-150998 2.0 mg	Stage 3: AGN-150998 1.0 mg	Stage 3: Ranibizumab 0.5 mg
Number of subjects analysed	23	25	16
Units: letters
arithmetic mean (standard deviation)
Baseline	58.5 ± 14.29	58.4 ± 13.49	60.4 ± 16.41
Change from Baseline at Week 16	8.2 ± 7.89	6.3 ± 7.81	5.3 ± 11.08

No statistical analyses for this end point

Secondary: Stage 2: Time between Second Treatment and Recurrence of Active Disease

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End point title

Stage 2: Time between Second Treatment and Recurrence of Active Disease ^[8]

End point description

Recurrence of active disease is defined as the time in days to escape to standard of care. Time is calculated as (date of Escaping to Standard of Care/Censoring minus the date of the Second Injection) +1. Inter-Quartile Range High value result of 99999.99=Not estimable.

End point type

Secondary

End point timeframe

32 Weeks

Notes
[8] - 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: Not all arms in the baseline period are applicable to this outcome measure.

End point values	Stage 2: AGN-150998 4.2 mg	Stage 2: AGN-150998 3.0 mg	Stage 2: Ranibizumab 0.5 mg
Number of subjects analysed	62	55	58
Units: days
median (inter-quartile range (Q1-Q3))	85 (57 to 118)	112 (60 to 99999.99)	111 (57 to 99999.99)

No statistical analyses for this end point

Secondary: Stage 2: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

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End point title

Stage 2: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye ^[9]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 4

Notes
[9] - 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: Not all arms in the baseline period are applicable to this outcome measure.

End point values	Stage 2: AGN-150998 4.2 mg	Stage 2: AGN-150998 3.0 mg	Stage 2: Ranibizumab 0.5 mg
Number of subjects analysed	65	57	57
Units: microns
arithmetic mean (standard deviation)
Baseline	524.6 ± 170.71	507.3 ± 139.88	497.1 ± 122.04
Change from Baseline at Week 4 (n=61,56,57)	-179.5 ± 123.76	-155.3 ± 109.13	-157.3 ± 121.95

No statistical analyses for this end point

Secondary: Stage 2: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye

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End point title

Stage 2: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye ^[10]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 4

Notes
[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: Not all arms in the baseline period are applicable to this outcome measure.

End point values	Stage 2: AGN-150998 4.2 mg	Stage 2: AGN-150998 3.0 mg	Stage 2: Ranibizumab 0.5 mg
Number of subjects analysed	65	57	57
Units: letters
arithmetic mean (standard deviation)
Baseline	54.5 ± 13.9	52.7 ± 12.62	55.4 ± 13
Change from Baseline at Week 4 (n=62,56,57)	4.7 ± 9.71	8.4 ± 11.51	5.9 ± 64

No statistical analyses for this end point

Secondary: Stage 3: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

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End point title

Stage 3: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye ^[11]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 4

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: Not all arms in the baseline period are applicable to this outcome measure.

End point values	Stage 3: AGN-150998 2.0 mg	Stage 3: AGN-150998 1.0 mg	Stage 3: Ranibizumab 0.5 mg
Number of subjects analysed	23	25	16
Units: microns
arithmetic mean (standard deviation)
Baseline	466 ± 125.96	526.1 ± 165.09	463.3 ± 94.56
Change from Baseline at Week 4	-119.8 ± 68.5	-168.3 ± 137.07	-98.4 ± 65.22

No statistical analyses for this end point

Secondary: Stage 3: Change from Baseline in BCVA in the Study Eye

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End point title

Stage 3: Change from Baseline in BCVA in the Study Eye ^[12]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 4

Notes
[12] - 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: Not all arms in the baseline period are applicable to this outcome measure.

End point values	Stage 3: AGN-150998 2.0 mg	Stage 3: AGN-150998 1.0 mg	Stage 3: Ranibizumab 0.5 mg
Number of subjects analysed	23	25	16
Units: letters
arithmetic mean (standard deviation)
Baseline	58.5 ± 14.29	58.4 ± 13.49	60.4 ± 16.41
Change from Baseline at Week 4	5 ± 7.4	4.6 ± 5.98	3.9 ± 6.01

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Stage 1: Up to 24 Weeks, Stage 2: Up to 32 Weeks and Stage 3: Up to 20 Weeks

Adverse event reporting additional description

Adverse Events (AEs) are analyzed and reported independently for Stage 1, Stage 2 and Stage 3, For non-serious Adverse Events, a result of 0 means there were no AEs greater than or equal to the threshold of 5% in the reporting group/arm.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.0

Reporting group title

Stage 1: AGN-150998 4.2 mg

Reporting group description

Stage 1: AGN-150998 4.2 mg given as a single intravitreal injection.

Reporting group title

Stage 1: AGN-150998 3.0 mg

Reporting group description

Stage 1: AGN-150998 3.0 mg given as a single intravitreal injection.

Reporting group title

Stage 1: AGN-150998 2.0 mg

Reporting group description

Stage 1: AGN-150998 2.0 mg given as a single intravitreal injection

Reporting group title

Stage 1: AGN-150998 1.0 mg

Reporting group description

Stage 1: AGN-150998 1.0 mg given as a single intravitreal injection.

Reporting group title

Stage 2: AGN-150998 4.2 mg

Reporting group description

Stage 2: AGN-150998 4.2 mg (highest tolerated dose from Stage 1) given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.

Reporting group title

Stage 2: Ranibizumab 0.5 mg

Reporting group description

Stage 2: ranibizumab 0.5 mg given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.

Reporting group title

Stage 2: AGN-150998 3.0 mg

Reporting group description

Stage 2: AGN-150998 3.0 mg (one dose below highest tolerated dose from Stage 1) given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.

Reporting group title

Stage 3: AGN-150998 1.0 mg

Reporting group description

Stage 3: AGN-150998 1.0 mg given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16.

Reporting group title

Stage 3: AGN-150998 2.0 mg

Reporting group description

Stage 3: AGN-150998 2.0 mg given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16.

Reporting group title

Stage 3: Ranibizumab 0.5 mg

Reporting group description

Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks

Serious adverse events	Stage 1: AGN-150998 4.2 mg	Stage 1: AGN-150998 3.0 mg	Stage 1: AGN-150998 2.0 mg	Stage 1: AGN-150998 1.0 mg	Stage 2: AGN-150998 4.2 mg	Stage 2: Ranibizumab 0.5 mg	Stage 2: AGN-150998 3.0 mg	Stage 3: AGN-150998 1.0 mg	Stage 3: AGN-150998 2.0 mg	Stage 3: Ranibizumab 0.5 mg
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	11 / 67 (16.42%)	5 / 58 (8.62%)	6 / 58 (10.34%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	1 / 58 (1.72%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal cell carcinoma
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	1 / 58 (1.72%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	1 / 58 (1.72%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal adenocarcinoma
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Temporal arteritis
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Aortic valve stenosis
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	1 / 58 (1.72%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	1 / 58 (1.72%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	1 / 58 (1.72%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Uveitus
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	3 / 67 (4.48%)	0 / 58 (0.00%)	2 / 58 (3.45%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	3 / 3	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anterior chamber inflammation
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 67 (2.99%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vitritis
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	0 / 58 (0.00%)	1 / 58 (1.72%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Choroiditis
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Glaucoma
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Optic ischaemic neuropathy
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Retinal artery occlusion
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Pancreatitis acute
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer haemorrhage
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	1 / 58 (1.72%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastric ulcer haemorrhage
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	1 / 58 (1.72%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure acute
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 67 (0.00%)	1 / 58 (1.72%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endophthalmitis
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	1 / 58 (1.72%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Stage 1: AGN-150998 4.2 mg	Stage 1: AGN-150998 3.0 mg	Stage 1: AGN-150998 2.0 mg	Stage 1: AGN-150998 1.0 mg	Stage 2: AGN-150998 4.2 mg	Stage 2: Ranibizumab 0.5 mg	Stage 2: AGN-150998 3.0 mg	Stage 3: AGN-150998 1.0 mg	Stage 3: AGN-150998 2.0 mg	Stage 3: Ranibizumab 0.5 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 9 (33.33%)	5 / 6 (83.33%)	4 / 6 (66.67%)	2 / 3 (66.67%)	35 / 67 (52.24%)	19 / 58 (32.76%)	20 / 58 (34.48%)	10 / 25 (40.00%)	6 / 23 (26.09%)	9 / 16 (56.25%)
Injury, poisoning and procedural complications
Laceration
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Contusion
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Vascular disorders
Hypertension
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	1 / 23 (4.35%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	1	1
Cardiac disorders
Palpitations
subjects affected / exposed	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Ventricular extrasystoles
subjects affected / exposed	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Nervous system disorders
Headache
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	3 / 58 (5.17%)	3 / 58 (5.17%)	0 / 25 (0.00%)	1 / 23 (4.35%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	2	5	3	0	1	1
Blood and lymphatic system disorders
Iron deficiency anaemia
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Eye disorders
Anterior chamber inflammation
subjects affected / exposed	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Retinal pigment epithelial tear
subjects affected / exposed	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Conjunctival haemorrhage
subjects affected / exposed	0 / 9 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 3 (33.33%)	9 / 67 (13.43%)	5 / 58 (8.62%)	3 / 58 (5.17%)	2 / 25 (8.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)
occurrences all number	0	1	1	1	9	5	5	4	1	0
Eye irritation
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 3 (0.00%)	5 / 67 (7.46%)	2 / 58 (3.45%)	2 / 58 (3.45%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	1	1	0	6	2	2	0	0	0
Anterior chamber cell
subjects affected / exposed	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Anterior chamber flare
subjects affected / exposed	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
Eye pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	6 / 67 (8.96%)	4 / 58 (6.90%)	3 / 58 (5.17%)	1 / 25 (4.00%)	2 / 23 (8.70%)	1 / 16 (6.25%)
occurrences all number	0	1	0	0	7	6	3	1	3	1
Hyalosis asteroid
subjects affected / exposed	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Macular oedema
subjects affected / exposed	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Foreign body sensation in eyes
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	4 / 67 (5.97%)	1 / 58 (1.72%)	0 / 58 (0.00%)	1 / 25 (4.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1	0	4	1	0	1	0	1
Retinal haemorrhage
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	6 / 67 (8.96%)	4 / 58 (6.90%)	3 / 58 (5.17%)	3 / 25 (12.00%)	0 / 23 (0.00%)	2 / 16 (12.50%)
occurrences all number	0	0	0	1	7	5	3	3	0	2
Vitreous detachment
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	5 / 67 (7.46%)	2 / 58 (3.45%)	6 / 58 (10.34%)	2 / 25 (8.00%)	2 / 23 (8.70%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	5	3	7	2	3	0
Visual acuity reduced
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	5 / 67 (7.46%)	3 / 58 (5.17%)	3 / 58 (5.17%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	6	5	8	0	0	0
Vitritis
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	3 / 58 (5.17%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	0	0
Vitreous floaters
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	0 / 58 (0.00%)	3 / 58 (5.17%)	3 / 25 (12.00%)	1 / 23 (4.35%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	1	0	3	3	1	1
Dry eye
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	1 / 58 (1.72%)	3 / 58 (5.17%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	1	5	0	0	0
Age-related macular degeneration
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 25 (4.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	1	0	1
Macular scar
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	2 / 16 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	2
Choroidal neovascularisation
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Eye pruritus
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	0	2
Ocular discomfort
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	0	2
Visual impairment
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Cough
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Oropharyngeal pain
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Urticaria
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Musculoskeletal and connective tissue disorders
Back pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	4 / 67 (5.97%)	2 / 58 (3.45%)	2 / 58 (3.45%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	4	2	2	0	0	0
Pain in extremity
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 67 (1.49%)	1 / 58 (1.72%)	3 / 58 (5.17%)	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	1	1	3	0	0	1
Infections and infestations
Urinary tract infection
subjects affected / exposed	1 / 9 (11.11%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	4 / 67 (5.97%)	1 / 58 (1.72%)	2 / 58 (3.45%)	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	2	0	0	0	5	1	5	0	0	1
Viral upper respiratory tract infection
subjects affected / exposed	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Influenza
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	3 / 58 (5.17%)	1 / 58 (1.72%)	0 / 25 (0.00%)	0 / 23 (0.00%)	2 / 16 (12.50%)
occurrences all number	0	0	0	0	0	3	1	0	0	2
Upper respiratory tract infection
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	1 / 23 (4.35%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	1	1
Bronchitis
subjects affected / exposed	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 67 (0.00%)	0 / 58 (0.00%)	0 / 58 (0.00%)	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	0	1

More information

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Were there any global substantial amendments to the protocol? Yes

12 Jul 2011

Amendment 1: An error in an inclusion criterion was corrected.

05 Dec 2011

Amendment 2: The protocol was amended to add a second injection of the study medication to assess the safety of repeat injection of the study medication and to add a cohort of Japanese patients to compare the safety, Pharmacokinetics (PK), and treatment effect of the study drug across ethnic groups.

24 Aug 2012

Amendment 3: The protocol was amended to add a potential interim analysis. Per protocol Population was used for Analysis. Week 16 Key Secondary time-point.

01 May 2013

Amendment 4: The protocol was amended to add a Stage 3 to explore the safety and effects of treatment with AGN-150998 administered at 4-week intervals on Best Corrected Visual Acuity (BCVA) and Central Retinal Thickness (CRT) versus ranibizumab.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
Single and Repeat Dose Study of the Safety and Efficacy of AGN-150998 in Patients with Exudative Age-related Macular Degeneration

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Highest Tolerated Dose (HTD) of AGN-150998

Primary: Highest Tolerated Dose (HTD) of AGN-150998

Primary: Stage 1: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

Primary: Stage 1: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

Primary: Stage 2: Time between Baseline Treatment and Recurrence of Active Disease

Primary: Stage 2: Time between Baseline Treatment and Recurrence of Active Disease

Primary: Stage 3: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye

Primary: Stage 3: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye

Secondary: Stage 2: Time between Second Treatment and Recurrence of Active Disease

Secondary: Stage 2: Time between Second Treatment and Recurrence of Active Disease

Secondary: Stage 2: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

Secondary: Stage 2: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

Secondary: Stage 2: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye

Secondary: Stage 2: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye

Secondary: Stage 3: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

Secondary: Stage 3: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

Secondary: Stage 3: Change from Baseline in BCVA in the Study Eye

Secondary: Stage 3: Change from Baseline in BCVA in the Study Eye

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Single and Repeat Dose Study of the Safety and Efficacy of AGN-150998 in Patients with Exudative Age-related Macular Degeneration

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Highest Tolerated Dose (HTD) of AGN-150998

Primary: Highest Tolerated Dose (HTD) of AGN-150998

Primary: Stage 1: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

Primary: Stage 1: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

Primary: Stage 2: Time between Baseline Treatment and Recurrence of Active Disease

Primary: Stage 2: Time between Baseline Treatment and Recurrence of Active Disease

Primary: Stage 3: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye

Primary: Stage 3: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye

Secondary: Stage 2: Time between Second Treatment and Recurrence of Active Disease

Secondary: Stage 2: Time between Second Treatment and Recurrence of Active Disease

Secondary: Stage 2: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

Secondary: Stage 2: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

Secondary: Stage 2: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye

Secondary: Stage 2: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye

Secondary: Stage 3: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

Secondary: Stage 3: Change from Baseline in Central Retinal Thickness (CRT) in the Study Eye

Secondary: Stage 3: Change from Baseline in BCVA in the Study Eye

Secondary: Stage 3: Change from Baseline in BCVA in the Study Eye

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Single and Repeat Dose Study of the Safety and Efficacy of AGN-150998 in Patients with Exudative Age-related Macular Degeneration