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Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study, with an Active-Treatment Dose-Blinded Period, to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Subjects with Parkinson’s Disease

Summary
EudraCT number	2016-004610-95
Trial protocol	GB AT DE FR ES IT
Global end of trial date	29 Apr 2021

Results information
Results version number	v1(current)
This version publication date	02 Apr 2022
First version publication date	02 Apr 2022
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

228PD201

ISRCTN number

US NCT number

NCT03318523

WHO universal trial number (UTN)

Sponsor organisation name

Biogen

Sponsor organisation address

250 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)

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

29 Apr 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

29 Apr 2021

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary objective of the study is to evaluate the clinical efficacy of BIIB054 via dose response using the change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score. The secondary objectives of the study are to evaluate the dose-related safety of BIIB054, to evaluate the clinical efficacy of BIIB054 via MDS-UPDRS total score, to assess the pharmacokinetic (PK) profile of BIIB054, to evaluate the clinical efficacy of BIIB054 based on MDS-UPDRS subparts, to evaluate the pharmacodynamic effects of BIIB054 on the integrity of nigrostriatal dopaminergic nerve terminals and to evaluate the immunogenicity of BIIB054.

Protection of trial subjects

Written informed consent was obtained from each subject or subject’s legally authorised representative (e.g., parent or legal guardian), as applicable, prior to evaluations performed for eligibility. Subjects or the subject’s legally authorised 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

Evidence for comparator

Actual start date of recruitment

10 Jan 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 167

Country: Number of subjects enrolled

Italy: 70

Country: Number of subjects enrolled

Spain: 48

Country: Number of subjects enrolled

Germany: 18

Country: Number of subjects enrolled

France: 19

Country: Number of subjects enrolled

Israel: 12

Country: Number of subjects enrolled

United Kingdom: 12

Country: Number of subjects enrolled

Canada: 8

Country: Number of subjects enrolled

Austria: 3

Worldwide total number of subjects

357

EEA total number of subjects

158

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)

232

From 65 to 84 years

125

85 years and over

Subject disposition

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Recruitment details

Subjects were enrolled at 75 investigational sites from 10 January 2018 to 29 April 2021.

Screening details

Subjects with Parkinson’s Disease(PD) were randomised to receive placebo or BIIB054 250/1250/3500 milligrams(mg) for Year 1 in Placebo-Controlled(PC) Period. After Year 1, those on placebo [delayed start (DS)] received BIIB054 250/1250/3500 mg, and others on BIIB054 in Year 1 continued to receive same dose until Week 96 visit.

Period 1 title

PC Period: Up to Year 1

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

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

Are arms mutually exclusive

Yes

PC Period: Placebo

Arm description

Subjects received BIIB054-matching placebo, intravenous (IV) infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Arm type

Placebo

Investigational medicinal product name

BIIB054-matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

BIIB054-matching placebo administered via IV infusion, on Day 1 and then every 4 weeks for Year 1.

PC Period: BIIB054 250 mg (Early Start)

Arm description

Subjects received BIIB054, 250 milligrams (mg), IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Arm type

Experimental

Investigational medicinal product name

BIIB054

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

BIIB054 250 mg administered via IV infusion, on Day 1 and then every 4 weeks for Year 1.

PC Period: BIIB054 1250 mg (Early Start)

Arm description

Subjects received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Arm type

Experimental

Investigational medicinal product name

BIIB054

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

BIIB054 1250 mg administered via IV infusion, on Day 1 and then every 4 weeks for Year 1.

PC Period: BIIB054 3500 mg (Early Start)

Arm description

Subjects received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Arm type

Experimental

Investigational medicinal product name

BIIB054

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

BIIB054 3500 mg administered via IV infusion, on Day 1 and then every 4 weeks for Year 1.

Number of subjects in period 1	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Started	100	55	102	100
Completed	96	53	100	96
Not completed	4	2	2	4
Adverse Event	1	-	2	-
Consent Withdrawn	3	2	-	4

Period 2 title

DBE Period:Year 2 to EOS (Up to 3 Years)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

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

Are arms mutually exclusive

Yes

DBE Period: Placebo to BIIB054 250 mg (DS)

Arm description

Subjects received BIIB054 250 mg, IV infusion from Year 2 up to end of study (EOS) (approximately 3 years) in the DBE Period. Subjects who received placebo in the PC period were included in this arm.

Arm type

Experimental

Investigational medicinal product name

BIIB054

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

BIIB054 250 mg administered via IV infusion, once every 4 weeks, from Year 2 up to EOS (approximately 3 years).

DBE Period: Placebo to BIIB054 1250 mg (DS)

Arm description

Subjects received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received placebo in the PC period were included in this arm.

Arm type

Experimental

Investigational medicinal product name

BIIB054

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

BIIB054 1250 mg administered via IV infusion, once every 4 weeks, from Year 2 up to EOS (approximately 3 years).

DBE Period: Placebo to BIIB054 3500 mg (DS)

Arm description

Subjects received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received placebo in the PC period were included in this arm.

Arm type

Experimental

Investigational medicinal product name

BIIB054

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

BIIB054 3500 mg administered via IV infusion, once every 4 weeks, from Year 2 up to EOS (approximately 3 years).

DBE Period: BIIB054 250 mg (Early Start)

Arm description

Subjects received BIIB054 250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received BIIB054 250 mg in the PC period were included in this arm.

Arm type

Experimental

Investigational medicinal product name

BIIB054

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

BIIB054 250 mg administered via IV infusion, once every 4 weeks, from Year 2 up to EOS (approximately 3 years).

DBE Period: BIIB054 1250 mg (Early Start)

Arm description

Subjects received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received BIIB054 1250 mg in the PC period were included in this arm.

Arm type

Experimental

Investigational medicinal product name

BIIB054

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

BIIB054 1250 mg administered via IV infusion, once every 4 weeks, from Year 2 up to EOS (approximately 3 years).

DBE Period: BIIB054 3500 mg (Early Start)

Arm description

Subjects received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received BIIB054 3500 mg in the PC period were included in this arm.

Arm type

Experimental

Investigational medicinal product name

BIIB054

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

BIIB054 3500 mg administered via IV infusion, once every 4 weeks, from Year 2 up to EOS (approximately 3 years).

Number of subjects in period 2 ^[1]	DBE Period: Placebo to BIIB054 250 mg (DS)	DBE Period: Placebo to BIIB054 1250 mg (DS)	DBE Period: Placebo to BIIB054 3500 mg (DS)	DBE Period: BIIB054 250 mg (Early Start)	DBE Period: BIIB054 1250 mg (Early Start)	DBE Period: BIIB054 3500 mg (Early Start)
Started	20	37	39	52	100	96
Number of Subjects Dosed	20	37	39	52	100	94
Completed	0	0	0	0	0	0
Not completed	20	37	39	52	100	96
Adverse Event	1	-	-	1	-	2
Death	-	-	-	-	-	1
Not Specified	1	-	-	2	3	-
Investigator Decision	-	1	-	-	-	-
Study Terminated by Sponsor	17	36	39	48	94	91
Consent Withdrawn	1	-	-	1	3	2

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: 345 subjects completed the PC Period, out of which only 344 subjects entered in DBE Period. 1 subject from PC Period did not enter DBE Period.

Baseline characteristics

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Reporting group title

PC Period: Placebo

Reporting group description

Subjects received BIIB054-matching placebo, intravenous (IV) infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Reporting group title

PC Period: BIIB054 250 mg (Early Start)

Reporting group description

Subjects received BIIB054, 250 milligrams (mg), IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Reporting group title

PC Period: BIIB054 1250 mg (Early Start)

Reporting group description

Subjects received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Reporting group title

PC Period: BIIB054 3500 mg (Early Start)

Reporting group description

Subjects received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Reporting group values	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)	Total
Number of subjects	100	55	102	100	357
Age Categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	61.0 ± 8.39	61.3 ± 9.24	59.2 ± 8.48	59.3 ± 9.92	-
Gender Categorical
Units: subjects
Female	28	16	29	34	107
Male	72	39	73	66	250
Race
Units: Subjects
American Indian or Alaska Native	0	0	0	2	2
Asian	0	0	3	3	6
Black or African American	0	0	1	0	1
White	96	53	92	84	325
Unknown or Not Reported	4	2	6	11	23
Ethnicity
Units: Subjects
Hispanic or Latino	3	1	1	6	11
Not Hispanic or Latino	96	54	101	94	345
Unknown or Not Reported	1	0	0	0	1
Baseline Movement Disorder Society Sponsored Revision of the Unified PD Rating Scale Total Score
Movement Disorder Society Sponsored Revision of the Unified PD Rating Scale (MDS-UPDRS) is multimodal scale assessing impairment and disability consisting of 4 parts. Part I: non-motor experiences of daily living and has 2 components (13 questions[Q], Range[R] 0-52). Part II: motor experiences of daily living (13 Q, R 0-52). Part III: motor signs of PD and was administered by rater (33 Q, R 0-132). Numeric score for each question is between 0-4; 0=Normal,1=Slight,2=Mild,3=Moderate,4=Severe. MDS-UPDRS Total Score=sum of Parts I, II, and III (R 0-236). Higher score=more severe symptoms of PD.
Units: score on a scale
arithmetic mean (standard deviation)	31.9 ± 12.41	31.9 ± 12.25	32.9 ± 12.58	32.6 ± 13.46	-
Baseline MDS-UPDRS Subpart I Score
MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. It is separated into 4 subscales: Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the subject (Range 0-28). For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD.
Units: score on a scale
arithmetic mean (standard deviation)	4.3 ± 3.50	3.3 ± 2.74	4.8 ± 3.99	4.3 ± 3.60	-
Baseline MDS-UPDRS Subpart II Score
MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the subject. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD.
Units: score on a scale
arithmetic mean (standard deviation)	5.4 ± 3.87	5.0 ± 3.30	5.3 ± 3.66	5.5 ± 4.30	-
Baseline MDS-UPDRS Subpart III Score
MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part III assessed the motor signs of Parkinson's Disease (PD) and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD.
Units: score on a scale
arithmetic mean (standard deviation)	22.2 ± 9.31	23.5 ± 9.38	22.8 ± 8.69	22.9 ± 8.86	-
Baseline Total Striatum Striatal Binding Ratio (SBR)
Number analysed is the number of subjects analysed for this study specific baseline measure: PC Period: Placebo (100), PC Period: BIIB054 250 mg (Early Start) (55), PC Period: BIIB054 1250 mg (Early Start) (102) and PC Period: BIIB054 3500 mg (Early Start) (99).
Units: striatal binding ratio
arithmetic mean (standard deviation)	1.295 ± 0.3177	1.409 ± 0.3875	1.342 ± 0.3197	1.351 ± 0.3495	-
Baseline Total Putamen SBR
Number analysed is the number of subjects analysed for this study specific baseline measure: PC Period: Placebo (100), PC Period: BIIB054 250 mg (Early Start) (55), PC Period: BIIB054 1250 mg (Early Start) (102) and PC Period: BIIB054 3500 mg (Early Start) (99).
Units: striatal binding ratio
arithmetic mean (standard deviation)	1.255 ± 0.3429	1.388 ± 0.4294	1.291 ± 0.3269	1.286 ± 0.3627	-
Baseline Total Caudate SBR
Number analysed is the number of subjects analysed for this study specific baseline measure: PC Period: Placebo (100), PC Period: BIIB054 250 mg (Early Start) (55), PC Period: BIIB054 1250 mg (Early Start) (102) and PC Period: BIIB054 3500 mg (Early Start) (99).
Units: striatal binding ratio
arithmetic mean (standard deviation)	1.336 ± 0.3279	1.433 ± 0.3751	1.397 ± 0.3417	1.416 ± 0.3643	-

End points

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Reporting group title

PC Period: Placebo

Reporting group description

Subjects received BIIB054-matching placebo, intravenous (IV) infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Reporting group title

PC Period: BIIB054 250 mg (Early Start)

Reporting group description

Subjects received BIIB054, 250 milligrams (mg), IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Reporting group title

PC Period: BIIB054 1250 mg (Early Start)

Reporting group description

Subjects received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Reporting group title

PC Period: BIIB054 3500 mg (Early Start)

Reporting group description

Subjects received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Reporting group title

DBE Period: Placebo to BIIB054 250 mg (DS)

Reporting group description

Subjects received BIIB054 250 mg, IV infusion from Year 2 up to end of study (EOS) (approximately 3 years) in the DBE Period. Subjects who received placebo in the PC period were included in this arm.

Reporting group title

DBE Period: Placebo to BIIB054 1250 mg (DS)

Reporting group description

Subjects received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received placebo in the PC period were included in this arm.

Reporting group title

DBE Period: Placebo to BIIB054 3500 mg (DS)

Reporting group description

Subjects received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received placebo in the PC period were included in this arm.

Reporting group title

DBE Period: BIIB054 250 mg (Early Start)

Reporting group description

Subjects received BIIB054 250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received BIIB054 250 mg in the PC period were included in this arm.

Reporting group title

DBE Period: BIIB054 1250 mg (Early Start)

Reporting group description

Subjects received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received BIIB054 1250 mg in the PC period were included in this arm.

Reporting group title

DBE Period: BIIB054 3500 mg (Early Start)

Reporting group description

Subjects received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received BIIB054 3500 mg in the PC period were included in this arm.

Subject analysis set title

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects who received BIIB054-matching placebo in Year 1 followed by BIIB054 250 mg or 1250 mg or 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) were pooled in this arm.

Subject analysis set title

PC Period: Early Start BIIB054 250 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Subject analysis set title

PC Period: Early Start BIIB054 1250 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.

Subject analysis set title

PC Period: Early Start BIIB054 3500 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.

Subject analysis set title

BIIB054 250 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects received BIIB054, 250 mg, IV infusion, from Day 1 up to EOS (approximately 3 years).

Subject analysis set title

BIIB054 1250 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects received BIIB054, 1250 mg, IV infusion, from Day 1 up to EOS (approximately 3 years).

Subject analysis set title

BIIB054 3500 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects received BIIB054, 3500 mg, IV infusion, from Day 1 up to EOS (approximately 3 years).

Subject analysis set title

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects who received BIIB054-matching placebo in Year 1 followed by BIIB054 250 mg or 1250 mg or 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) were pooled in this arm.

Subject analysis set title

PC Period: Early Start BIIB054 250 mg

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Subject analysis set title

PC Period: Early Start BIIB054 1250 mg

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.

Subject analysis set title

PC Period: Early Start BIIB054 3500 mg

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.

Subject analysis set title

PC Period: Placebo

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Subject analysis set title

PC Period: BIIB054 250 mg (Early Start)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Subject analysis set title

PC Period: BIIB054 1250 mg (Early Start)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.

Subject analysis set title

PC Period: BIIB054 3500 mg (Early Start)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.

Primary: Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52

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End point title

Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52

End point description

MDS-UPDRS is multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range [R] 0-52). Part IA: 6 questions (Qs) assessed by examiner (R 0-24). Part IB: 7 Qs completed by subject (R 0-28). Part II assessed motor experiences of daily living (R 0-52). It contained 13 Qs completed by subject. Part III assessed motor signs of PD and was administered by rater (R 0-132). Part III contained 33 scores based on 18 items. Numeric score for each question is between 0-4, where 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. MDS-UPDRS Total Score=sum of Parts I, II, and III (R 0-236). A higher score indicated more severe symptoms of PD. ITT Population. The mean values reported are the adjusted mean values.

End point type

Primary

End point timeframe

Baseline, Week 52

End point values	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Number of subjects analysed	53 ^[1]	29 ^[2]	57 ^[3]	51 ^[4]
Units: score on a scale
arithmetic mean (standard error)	10.78 ± 1.490	10.48 ± 1.951	11.29 ± 1.446	10.86 ± 1.518

Notes
[1] - Number of subjects analysed were subjects analysed for this endpoint.
[2] - Number of subjects analysed were subjects analysed for this endpoint.
[3] - Number of subjects analysed were subjects analysed for this endpoint.
[4] - Number of subjects analysed were subjects analysed for this endpoint.

Week 52: Placebo vs BIIB054 250 mg

Statistical analysis description

Adjusted mean, difference with placebo, 95% confidence interval (CI), and p-value were based on a mixed model for repeated measures (MMRM) model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.

Comparison groups

PC Period: BIIB054 250 mg (Early Start) v PC Period: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8976

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-4.888

upper limit

4.287

Week 52: Placebo vs BIIB054 1250 mg

Statistical analysis description

Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.

Comparison groups

PC Period: Placebo v PC Period: BIIB054 1250 mg (Early Start)

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.796

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.31

upper limit

4.312

Week 52: Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 3500 mg (Early Start)

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9695

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-3.805

upper limit

3.956

Primary: Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 72

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End point title

Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 72

End point description

MDS-UPDRS is multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range [R] 0-52). Part IA: 6 questions (Qs) assessed by examiner (R 0-24). Part IB: 7 Qs completed by subject (R 0-28). Part II assessed motor experiences of daily living (R 0-52). It contained 13 Qs completed by subject. Part III assessed motor signs of PD and was administered by rater (R 0-132). Part III contained 33 scores based on 18 items. Numeric score for each question is between 0-4, where 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. MDS-UPDRS Total Score=sum of Parts I, II, and III (R 0-236). Higher score=severe symptoms of PD. ITT Population. As prespecified in protocol, data for delayed start BIIB054 were pooled from Placebo/BIIB054 250/1250/3500 mg for analysis of this endpoint. The mean values reported=adjusted mean values.

End point type

Primary

End point timeframe

Baseline, Week 72

End point values	PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Number of subjects analysed	68 ^[5]	32 ^[6]	62 ^[7]	64 ^[8]
Units: score on a scale
arithmetic mean (standard error)	7.11 ± 1.476	6.83 ± 2.032	8.66 ± 1.496	6.94 ± 1.508

Notes
[5] - Number of subjects analysed were subjects analysed for this endpoint.
[6] - Number of subjects analysed were subjects analysed for this endpoint.
[7] - Number of subjects analysed were subjects analysed for this endpoint.
[8] - Number of subjects analysed were subjects analysed for this endpoint.

Week 72: Pooled Placebo vs BIIB054 250 mg

Statistical analysis description

Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 250 mg

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9093

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-5.035

upper limit

4.483

Week 72: Pooled Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 1250 mg

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4327

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

1.55

Confidence interval

level

95%

sides

2-sided

lower limit

-2.336

upper limit

5.44

Week 72: Pooled Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 3500 mg

Number of subjects included in analysis

132

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.933

Method

Mixed Model with repeated Measures

Parameter type

Difference

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-4.051

upper limit

3.719

Secondary: Percentage of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

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End point title

Percentage of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

End point description

An AE is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavourable 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. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the subject at immediate risk of death; requires inpatient hospitalisation or prolongation of existing hospitalisation; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event. The safety population was defined as all subjects who received at least one dose of study treatment (BIIB054).

End point type

Secondary

End point timeframe

Up to 3 years

End point values	PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Number of subjects analysed	96	55	102	100
Units: percentage of subjects
number (not applicable)
AEs	77.1	85.5	89.2	93.0
SAEs	8.3	10.9	8.8	12.0

No statistical analyses for this end point

Secondary: Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96

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End point title

Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96

End point description

MDS-UPDRS is multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range [R] 0-52). Part IA: 6 questions (Qs) assessed by examiner (R 0-24). Part IB: 7 Qs completed by subject (R 0-28). Part II assessed motor experiences of daily living (R 0-52). It contained 13 Qs completed by subject. Part III assessed motor signs of PD and was administered by rater (R 0-132). Part III contained 33 scores based on 18 items. Numeric score for each question is between 0-4, where 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. MDS-UPDRS Total Score=sum of Parts I, II, and III (R 0-236). Higher score=Severe symptoms of PD. ITT population. As prespecified in protocol, data for delayed start BIIB054 were pooled from Placebo/BIIB054 250/1250/3500 mg for analysis of this endpoint. The mean values reported are the adjusted mean values.

End point type

Secondary

End point timeframe

Baseline, Week 96

End point values	PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Number of subjects analysed	67 ^[9]	28 ^[10]	62 ^[11]	59 ^[12]
Units: score on a scale
arithmetic mean (standard error)	7.88 ± 1.616	8.28 ± 2.317	8.71 ± 1.628	8.87 ± 1.659

Notes
[9] - Number of subjects analysed were subjects analysed for this endpoint.
[10] - Number of subjects analysed were subjects analysed for this endpoint.
[11] - Number of subjects analysed were subjects analysed for this endpoint.
[12] - Number of subjects analysed were subjects analysed for this endpoint.

Week 96: Pooled Placebo vs BIIB054 250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 250 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8828

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.41

Confidence interval

level

95%

sides

2-sided

lower limit

-5.013

upper limit

5.825

Week 96: Pooled Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 1250 mg

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7019

Method

Mixed Model for Repeated Measure

Parameter type

Difference

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

-3.458

upper limit

5.128

Week 96: Pooled Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 3500 mg

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6519

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

-3.323

upper limit

5.301

Secondary: Serum Concentration of BIIB054

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End point title

Serum Concentration of BIIB054

End point description

The pharmacokinetic (PK) population was defined as all subjects in the ITT population who had at least one measurable BIIB054 concentration in serum or cerebrospinal fluid (CSF). The 'n' signifies the number of subjects analysed at the specified time point. ‘99999’ signifies that mean and SD were non-determinable.

End point type

Secondary

End point timeframe

Pre-dose and 1 hour post-dose of Baseline, Weeks 4, 8, 12, 16, 24, 32, 36, 44, 52, 60, 68, 84, 96, 120 and 144

End point values	BIIB054 250 mg	BIIB054 1250 mg	BIIB054 3500 mg
Number of subjects analysed	75	139	139
Units: micrograms per millilitre (ug/mL)
arithmetic mean (standard deviation)
Baseline (Pre-dose) (n=48,95,92)	0 ± 0	7.47 ± 51.281	0.01 ± 0.065
Baseline (1 Hour Post-dose) (n=62,121,114)	75.02 ± 15.829	374.79 ± 86.004	1137.28 ± 335.336
Week 4 (Pre-dose) (n=46,95,91)	20.37 ± 5.004	95.36 ± 27.882	306.20 ± 95.257
Week 4 (1 Hour Post-dose) (n=47,94,91)	97.09 ± 19.711	468.56 ± 190.589	1354.19 ± 364.468
Week 8 (Pre-dose) (n=63,125,122)	29.73 ± 8.371	169.79 ± 68.025	495.79 ± 153.357
Week 8 (1 Hour Post-dose) (n=64,127,122)	103.69 ± 26.964	543.91 ± 143.212	1591.57 ± 465.798
Week 12 (Pre-dose) (n=50,97,96)	36.76 ± 11.830	195.16 ± 51.020	580.43 ± 185.761
Week 12 (1 Hour Post-dose) (n=54,99,97)	112.61 ± 27.378	569.41 ± 141.250	1632.29 ± 459.839
Week 16 (Pre-dose) (n=51,99,98)	40.82 ± 11.421	201.33 ± 73.451	642.06 ± 194.288
Week 16 (1 Hour Post-dose) (n=50,99,98)	117.08 ± 27.401	614.85 ± 186.892	1739.98 ± 506.346
Week 24 (Pre-dose) (n=54,98,94)	43.31 ± 12.906	235.69 ± 84.454	724.60 ± 228.295
Week 24 (1 Hour Post-dose) (n=46,90,87)	125.79 ± 36.695	664.26 ± 209.251	1867.92 ± 470.283
Week 32 (Pre-dose) (n=11,19,24)	42.69 ± 13.486	260.35 ± 104.397	772.75 ± 299.703
Week 32 (1 Hour Post-dose) (n=15,25,28)	139.00 ± 34.758	626.16 ± 164.497	1985.71 ± 497.545
Week 36 (Pre-dose) (n=51,100,96)	45.77 ± 11.867	262.80 ± 85.052	819.83 ± 328.774
Week 36 (1 Hour Post-dose) (n=51,100,95)	123.67 ± 29.536	665.60 ± 145.235	1916.84 ± 543.373
Week 44 (Pre-dose) (n=3,5,7)	58.17 ± 22.774	280.40 ± 116.590	858.43 ± 349.573
Week 44 (1 Hour Post-dose) (n=3,5,8)	143.33 ± 41.004	582.40 ± 194.431	2066.25 ± 579.555
Week 52 (Pre-dose) (n=49,98,82)	46.70 ± 19.343	232.08 ± 87.529	787.35 ± 341.229
Week 52 (1 Hour Post-dose) (n=35,74,64)	114.59 ± 25.913	645.36 ± 264.270	1920.78 ± 479.511
Week 60 (Pre-dose) (n=42,86,84)	43.41 ± 15.973	254.52 ± 88.446	724.77 ± 314.854
Week 60 (1 Hour Post-dose) (n=41,83,80)	122.55 ± 29.374	657.94 ± 149.654	1905.43 ± 494.136
Week 68 (Pre-dose) (n=2,3,2)	706.25 ± 966.969	202.33 ± 34.210	1362.50 ± 533.866
Week 68 (1 Hour Post-dose) (n=2,3,2)	171.50 ± 44.548	576.33 ± 85.290	2305.00 ± 1025.305
Week 84 (Pre-dose) (n=28,50,42)	47.00 ± 15.535	255.54 ± 81.407	746.43 ± 249.770
Week 84 (1 Hour Post-dose) (n=38,60,52)	134.91 ± 33.035	648.62 ± 120.163	1942.02 ± 501.095
Week 96 (Pre-dose) (n=11,18,16)	41.25 ± 15.345	274.56 ± 71.718	654.70 ± 262.926
Week 96 (1 Hour Post-dose) (n=10,20,16)	122.00 ± 29.527	682.30 ± 123.653	1822.50 ± 475.682
Week 120 (Pre-dose) (n=6,6,7)	34.98 ± 12.042	279.00 ± 99.499	727.29 ± 116.793
Week 120 (1 Hour Post-dose) (n=6,6,7)	119.67 ± 15.629	769.83 ± 279.182	1717.14 ± 320.037
Week 144 (Pre-dose) (n=0,1,0)	99999 ± 99999	365.00 ± 99999	99999 ± 99999
Week 144 (1 Hour Post-dose) (n=0,1,0)	99999 ± 99999	721.00 ± 99999	99999 ± 99999

No statistical analyses for this end point

Secondary: Change From Baseline in MDS-UPDRS Subpart I Score at Week 52

Top of page

End point title

Change From Baseline in MDS-UPDRS Subpart I Score at Week 52

End point description

MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the subject (Range 0-28). For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The ITT population was defined as all randomised subjects who received at least one dose of study treatment (BIIB054 or placebo). The mean values reported are the adjusted mean values.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Number of subjects analysed	53 ^[13]	29 ^[14]	57 ^[15]	51 ^[16]
Units: score on a scale
arithmetic mean (standard error)	1.43 ± 0.436	0.90 ± 0.570	1.56 ± 0.423	1.65 ± 0.446

Notes
[13] - Number of subjects analysed were subjects analysed for this endpoint.
[14] - Number of subjects analysed were subjects analysed for this endpoint.
[15] - Number of subjects analysed were subjects analysed for this endpoint.
[16] - Number of subjects analysed were subjects analysed for this endpoint.

Week 52: Placebo vs BIIB054 250 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 250 mg (Early Start)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4327

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-1.851

upper limit

0.794

Week 52: Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 1250 mg (Early Start)

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8155

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.13

Confidence interval

level

95%

sides

2-sided

lower limit

-0.965

upper limit

1.225

Week 52: Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 3500 mg (Early Start)

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7015

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.899

upper limit

1.334

Secondary: Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96

Top of page

End point title

Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96

End point description

MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the subject (Range 0-28). For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The ITT population was defined as all randomised subjects who received at least one dose of study treatment (BIIB054 or placebo). As prespecified in the protocol, the data for the delayed start BIIB054 were pooled from Placebo/BIIB054 250/1250/3500 mg for the analysis of this endpoint. The 'n' signifies number of subjects analysed at the specified time point. The mean values reported are the adjusted mean values.

End point type

Secondary

End point timeframe

Baseline, Weeks 72 and 96

End point values	PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Number of subjects analysed	100	55	102	100
Units: score on a scale
arithmetic mean (standard error)
Change from Baseline at Week 72 (n=68,32,62,64)	1.65 ± 0.395	0.61 ± 0.538	1.73 ± 0.402	1.63 ± 0.405
Change from Baseline at Week 96 (n=67,28,62,59)	1.95 ± 0.398	1.69 ± 0.568	1.93 ± 0.403	1.72 ± 0.414

Week 72: Pooled Placebo vs BIIB054 250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 250 mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1038

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-1.03

Confidence interval

level

95%

sides

2-sided

lower limit

-2.276

upper limit

0.213

Week 72: Pooled Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 1250 mg

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8689

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.933

upper limit

1.103

Week 72: Pooled Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 3500 mg

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.982

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-1.026

upper limit

1.003

Week 96: Pooled Placebo vs BIIB054 250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 250 mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.693

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-1.563

upper limit

1.04

Week 96: Pooled Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 1250 mg

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9606

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-1.053

upper limit

1.001

Week 96: Pooled Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 3500 mg

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6512

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-1.269

upper limit

0.794

Secondary: Change From Baseline in MDS-UPDRS Subpart II Score at Week 52

Top of page

End point title

Change From Baseline in MDS-UPDRS Subpart II Score at Week 52

End point description

MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the subject. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The ITT population was defined as all randomised subjects who received at least one dose of study treatment (BIIB054 or placebo). The mean values reported are the adjusted mean values.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Number of subjects analysed	54 ^[17]	29 ^[18]	58 ^[19]	51 ^[20]
Units: score on a scale
arithmetic mean (standard error)	3.17 ± 0.473	2.72 ± 0.621	3.16 ± 0.460	3.01 ± 0.486

Notes
[17] - Number of subjects analysed were subjects analysed for this endpoint.
[18] - Number of subjects analysed were subjects analysed for this endpoint.
[19] - Number of subjects analysed were subjects analysed for this endpoint.
[20] - Number of subjects analysed were subjects analysed for this endpoint.

Week 52: Placebo vs BIIB054 250 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 250 mg (Early Start)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5497

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.44

Confidence interval

level

95%

sides

2-sided

lower limit

-1.889

upper limit

1.007

Week 52: Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 1250 mg (Early Start)

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.998

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

1.197

Week 52: Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 3500 mg (Early Start)

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8069

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-1.374

upper limit

1.07

Secondary: Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96

Top of page

End point title

Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96

End point description

MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the subject. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The ITT population was defined as all randomised subjects who received at least one dose of study treatment (BIIB054 or placebo). As prespecified in the protocol, the data for the delayed start BIIB054 were pooled from (Placebo/BIIB054 250/1250/3500 mg) for the analysis of this endpoint. The 'n' signifies number of subjects analysed at the specified time point. The mean values reported are the adjusted mean values.

End point type

Secondary

End point timeframe

Baseline, Weeks 72 and 96

End point values	PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Number of subjects analysed	100	55	102	100
Units: score on a scale
arithmetic mean (standard error)
Change from Baseline at Week 72 (n=69,33,62,64)	1.83 ± 0.491	1.62 ± 0.672	2.36 ± 0.497	1.68 ± 0.503
Change from Baseline at Week 96 (n=67,28,62,60)	1.87 ± 0.529	1.33 ± 0.762	2.39 ± 0.533	2.22 ± 0.541

Week 72: Pooled Placebo vs BIIB054 250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 250 mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7968

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-1.786

upper limit

1.372

Week 72: Pooled Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 1250 mg

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4211

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-0.766

upper limit

1.827

Week 72: Pooled Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 3500 mg

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8166

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-1.448

upper limit

1.143

Week 96: Pooled Placebo vs BIIB054 250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 250 mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5535

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-2.31

upper limit

1.24

Week 96: Pooled Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 1250 mg

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4654

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.52

Confidence interval

level

95%

sides

2-sided

lower limit

-0.881

upper limit

1.922

Week 96: Pooled Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 3500 mg

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6184

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-1.051

upper limit

1.763

Secondary: Change From Baseline in MDS-UPDRS Subpart III Score at Week 52

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End point title

Change From Baseline in MDS-UPDRS Subpart III Score at Week 52

End point description

MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The ITT population was defined as all randomised subjects who received at least one dose of study treatment (BIIB054 or placebo). The mean values reported are the adjusted mean values.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Number of subjects analysed	53 ^[21]	29 ^[22]	58 ^[23]	51 ^[24]
Units: score on a scale
arithmetic mean (standard error)	6.10 ± 1.083	6.69 ± 1.419	6.76 ± 1.046	6.20 ± 1.104

Notes
[21] - Number of subjects analysed were subjects analysed for this endpoint.
[22] - Number of subjects analysed were subjects analysed for this endpoint.
[23] - Number of subjects analysed were subjects analysed for this endpoint.
[24] - Number of subjects analysed were subjects analysed for this endpoint.

Week 52: Placebo vs BIIB054 250 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 250 mg (Early Start)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7274

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-2.742

upper limit

3.925

Week 52: Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 1250 mg (Early Start)

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6385

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-2.094

upper limit

3.411

Week 52: Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 3500 mg (Early Start)

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9467

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.718

upper limit

2.91

Secondary: Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96

Top of page

End point title

Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96

End point description

MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The ITT population was defined as all randomised subjects who received at least one dose of study treatment (BIIB054 or placebo). As prespecified in the protocol, the data for the delayed start BIIB054 were pooled from (Placebo/BIIB054 250/1250/3500 mg) for the analysis of this endpoint. The 'n' signifies number of subjects analysed at the specified time point. The mean values reported are the adjusted mean values.

End point type

Secondary

End point timeframe

Baseline, Weeks 72 and 96

End point values	PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Number of subjects analysed	100	55	102	100
Units: score on a scale
arithmetic mean (standard error)
Change from Baseline at Week 72 (n=68,32,62,64)	3.64 ± 1.027	4.48 ± 1.404	4.49 ± 1.038	3.69 ± 1.048
Change from Baseline at Week 96 (n=67,28,62,60)	4.49 ± 1.174	5.14 ± 1.679	4.39 ± 1.180	5.17 ± 1.201

Week 72: Pooled Placebo vs BIIB054 250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 250 mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6112

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

-2.423

upper limit

4.114

Week 72: Pooled Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 3500 mg

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9673

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-2.608

upper limit

2.719

Week 72: Pooled Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 1250 mg

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.527

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

-1.806

upper limit

3.52

Week 96: Pooled Placebo vs BIIB054 250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 250 mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7455

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

-3.274

upper limit

4.569

Week 96: Pooled Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 1250 mg

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9506

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.192

upper limit

2.997

Week 96: Pooled Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled) v PC Period: Early Start BIIB054 3500 mg

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6643

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-2.422

upper limit

3.794

Secondary: Change From Baseline in Striatal Binding Ratio (SBR) in the Putamen as Measured by Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter (DaT) at Week 52

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End point title

Change From Baseline in Striatal Binding Ratio (SBR) in the Putamen as Measured by Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter (DaT) at Week 52

End point description

SBR in the putamen as measured by SPECT imaging of the dopamine transporter (DaT) with 123^I-ioflupane (DaTscan™). The pharmacodynamic population was defined as a subset of the ITT population with at least 1 post-baseline pharmacodynamic measurement. The mean values reported are the adjusted mean values.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Number of subjects analysed	91	52	97	84
Units: SBR
arithmetic mean (standard error)	-0.093 ± 0.0151	-0.098 ± 0.0199	-0.102 ± 0.0146	-0.125 ± 0.0155

Week 52: Placebo vs BIIB054 250 mg

Statistical analysis description

Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in DaT/SPECT parameter as dependent variable and with fixed effects of treatment group, region, time, treatment group-by-time interaction, baseline MDS-UPDRS part I+II+III total score, baseline MDS-UPDRS part I+II+III total score by time interaction, baseline DaT/SPECT values and baseline DaT/SPECT by time interaction.

Comparison groups

PC Period: Placebo v PC Period: BIIB054 250 mg (Early Start)

Number of subjects included in analysis

143

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8274

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.005

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0548

upper limit

0.0438

Week 52: Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 1250 mg (Early Start)

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6671

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.009

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0504

upper limit

0.0323

Week 52: Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 3500 mg (Early Start)

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1313

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.033

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0751

upper limit

0.0098

Secondary: Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52

Top of page

End point title

Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52

End point description

SBR in the striatum as measured by SPECT imaging of the DaT with 123^I-ioflupane (DaTscan™). The pharmacodynamic population was defined as a subset of the ITT population with at least 1 post-baseline pharmacodynamic measurement. The mean values reported are the adjusted mean values.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Number of subjects analysed	91	52	97	84
Units: SBR
arithmetic mean (standard error)	-0.081 ± 0.0145	-0.090 ± 0.0191	-0.081 ± 0.0140	-0.108 ± 0.0148

Week 52: Placebo vs BIIB054 250 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 250 mg (Early Start)

Number of subjects included in analysis

143

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7079

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.009

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0562

upper limit

0.0382

Week 52: Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 1250 mg (Early Start)

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9835

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04

upper limit

0.0392

Week 52: Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 3500 mg (Early Start)

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1869

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.027

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0682

upper limit

0.0134

Secondary: Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52

Top of page

End point title

Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52

End point description

SBR in the caudate as measured by SPECT imaging of the DaT with 123^I-ioflupane (DaTscan™). The pharmacodynamic population was defined as a subset of the ITT population with at least 1 post-baseline pharmacodynamic measurement. The mean values reported are the adjusted mean values.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Number of subjects analysed	91	52	97	84
Units: SBR
arithmetic mean (standard error)	-0.067 ± 0.0166	-0.075 ± 0.0219	-0.060 ± 0.0161	-0.089 ± 0.0171

Week 52: Placebo vs BIIB054 250 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 250 mg (Early Start)

Number of subjects included in analysis

143

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7585

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.008

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0625

upper limit

0.0456

Week 52: Placebo vs BIIB054 1250 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 1250 mg (Early Start)

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7808

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

0.006

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0391

upper limit

0.052

Week 52: Placebo vs BIIB054 3500 mg

Statistical analysis description

Comparison groups

PC Period: Placebo v PC Period: BIIB054 3500 mg (Early Start)

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3532

Method

Mixed Model for Repeated Measures

Parameter type

Difference

Point estimate

-0.022

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0691

upper limit

0.0248

Secondary: Percentage of Subjects With Anti-BIIB054 Antibodies in the Serum

Top of page

End point title

Percentage of Subjects With Anti-BIIB054 Antibodies in the Serum

End point description

The analysis population for immunogenicity was defined as all subjects in the safety population. As prespecified in the protocol, the data for the delayed start BIIB054 were pooled from Placebo/BIIB054 250/1250/3500 mg for the analysis of this endpoint.

End point type

Secondary

End point timeframe

Up to Week 144

End point values	PC Period:Placebo to BIIB054 250/1250/3500 mg (DS-Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Number of subjects analysed	96	55	100	99
Units: percentage of subjects
number (not applicable)	0	1.8	0	0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Up to 3 years

Adverse event reporting additional description

Safety Population included all subjects who received at least one dose of the study treatment (BIIB054 250 mg, 1250 mg, 3500 mg).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

PC Period: Placebo

Reporting group description

Subjects received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Reporting group title

PC Period: BIIB054 250 mg (Early Start)

Reporting group description

Subjects received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Reporting group title

PC Period: BIIB054 1250 mg (Early Start)

Reporting group description

Subjects received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Reporting group title

PC Period: BIIB054 3500 mg (Early Start)

Reporting group description

Subjects received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.

Reporting group title

DBE Period: Placebo to BIIB054 250 mg (Delayed Start)

Reporting group description

Subjects received BIIB054 250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received placebo in the PC period were included in this arm.

Reporting group title

DBE Period: BIIB054 250 mg (Early Start)

Reporting group description

Subjects received BIIB054 250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received BIIB054 250 mg in the PC period were included in this arm.

Reporting group title

DBE Period: Placebo to BIIB054 1250 mg (Delayed Start)

Reporting group description

Subjects received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received placebo in the PC period were included in this arm.

Reporting group title

DBE Period: Placebo to BIIB054 3500 mg (Delayed Start)

Reporting group description

Subjects received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received placebo in the PC period were included in this arm.

Reporting group title

DBE Period: BIIB054 1250 mg (Early Start)

Reporting group description

Subjects received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received BIIB054 1250 mg in the PC period were included in this arm.

Reporting group title

DBE Period: BIIB054 3500 mg (Early Start)

Reporting group description

Subjects received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Subjects who received BIIB054 3500 mg in the PC period were included in this arm.

Serious adverse events	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)	DBE Period: Placebo to BIIB054 250 mg (Delayed Start)	DBE Period: BIIB054 250 mg (Early Start)	DBE Period: Placebo to BIIB054 1250 mg (Delayed Start)	DBE Period: Placebo to BIIB054 3500 mg (Delayed Start)	DBE Period: BIIB054 1250 mg (Early Start)	DBE Period: BIIB054 3500 mg (Early Start)
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 100 (7.00%)	4 / 55 (7.27%)	4 / 102 (3.92%)	6 / 100 (6.00%)	2 / 20 (10.00%)	3 / 52 (5.77%)	3 / 37 (8.11%)	3 / 39 (7.69%)	5 / 100 (5.00%)	7 / 94 (7.45%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	1
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	1 / 100 (1.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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
Glioblastoma
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	1 / 100 (1.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	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
Invasive lobular breast carcinoma
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (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
Prostate cancer
subjects affected / exposed	0 / 100 (0.00%)	1 / 55 (1.82%)	0 / 102 (0.00%)	1 / 100 (1.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	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
General disorders and administration site conditions
Impaired healing
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	1 / 100 (1.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	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
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (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
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	1 / 100 (1.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	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
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	1 / 100 (1.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	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
Psychiatric disorders
Depression
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	1 / 100 (1.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	1 / 39 (2.56%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	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
Suicidal ideation
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	1 / 102 (0.98%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (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
Injury, poisoning and procedural complications
Arthropod sting
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (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
Fall
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	1 / 100 (1.00%)	0 / 20 (0.00%)	1 / 52 (1.92%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	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
Femur fracture
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	1 / 100 (1.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	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
Jaw fracture
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	1 / 52 (1.92%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (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
Muscle strain
subjects affected / exposed	1 / 100 (1.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	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
Pelvic fracture
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
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
Post lumbar puncture syndrome
subjects affected / exposed	1 / 100 (1.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	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
Road traffic accident
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
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
Spinal compression fracture
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
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
Ulna fracture
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
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
Palpitations
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	1 / 100 (1.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	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
Pericarditis
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	1 / 102 (0.98%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 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
Sinus bradycardia
subjects affected / exposed	0 / 100 (0.00%)	1 / 55 (1.82%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	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
Bradycardia
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (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
Myocardial infarction
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
Nervous system disorders
Intracranial mass
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	1 / 100 (1.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	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
Sciatica
subjects affected / exposed	1 / 100 (1.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	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
Transient ischaemic attack
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	1 / 100 (1.00%)	1 / 20 (5.00%)	1 / 52 (1.92%)	0 / 37 (0.00%)	0 / 39 (0.00%)	1 / 100 (1.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 1	1 / 1	0 / 0	0 / 0	0 / 1	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
Blood and lymphatic system disorders
Monoclonal B-cell lymphocytosis
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
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
Small intestinal obstruction
subjects affected / exposed	1 / 100 (1.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	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
Hepatobiliary disorders
Hepatitis toxic
subjects affected / exposed	1 / 100 (1.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	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
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	1 / 102 (0.98%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (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
Musculoskeletal and connective tissue disorders
Arthritis
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
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
Back pain
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
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
Lumbar spinal stenosis
subjects affected / exposed	0 / 100 (0.00%)	1 / 55 (1.82%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	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
Musculoskeletal chest pain
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
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
Osteoarthritis
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	1 / 39 (2.56%)	1 / 100 (1.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	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
Rotator cuff syndrome
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	1 / 102 (0.98%)	0 / 100 (0.00%)	0 / 20 (0.00%)	1 / 52 (1.92%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (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
Spinal stenosis
subjects affected / exposed	0 / 100 (0.00%)	1 / 55 (1.82%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	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
Spondylolisthesis
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	1 / 39 (2.56%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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
Perirectal abscess
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
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
Viral infection
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
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
COVID-19
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (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
COVID-19 pneumonia
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	1 / 37 (2.70%)	0 / 39 (0.00%)	1 / 100 (1.00%)	0 / 94 (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 / 1	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
Gastroenteritis viral
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	1 / 100 (1.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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
Gastroenteritis
subjects affected / exposed	1 / 100 (1.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	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

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

Non-serious adverse events	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)	DBE Period: Placebo to BIIB054 250 mg (Delayed Start)	DBE Period: BIIB054 250 mg (Early Start)	DBE Period: Placebo to BIIB054 1250 mg (Delayed Start)	DBE Period: Placebo to BIIB054 3500 mg (Delayed Start)	DBE Period: BIIB054 1250 mg (Early Start)	DBE Period: BIIB054 3500 mg (Early Start)
Total subjects affected by non serious adverse events
subjects affected / exposed	58 / 100 (58.00%)	32 / 55 (58.18%)	61 / 102 (59.80%)	63 / 100 (63.00%)	16 / 20 (80.00%)	25 / 52 (48.08%)	22 / 37 (59.46%)	22 / 39 (56.41%)	51 / 100 (51.00%)	56 / 94 (59.57%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of skin
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	1 / 52 (1.92%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences all number	0	0	0	0	1	1	0	0	0	3
Vascular disorders
Hypertension
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	2 / 37 (5.41%)	2 / 39 (5.13%)	5 / 100 (5.00%)	2 / 94 (2.13%)
occurrences all number	0	0	0	0	0	0	2	2	6	2
General disorders and administration site conditions
Fatigue
subjects affected / exposed	5 / 100 (5.00%)	2 / 55 (3.64%)	3 / 102 (2.94%)	9 / 100 (9.00%)	1 / 20 (5.00%)	1 / 52 (1.92%)	0 / 37 (0.00%)	0 / 39 (0.00%)	4 / 100 (4.00%)	5 / 94 (5.32%)
occurrences all number	5	3	4	25	1	1	0	0	4	14
Asthenia
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences all number	0	0	0	0	2	0	0	0	0	1
Reproductive system and breast disorders
Erectile dysfunction
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	2 / 39 (5.13%)	1 / 100 (1.00%)	1 / 94 (1.06%)
occurrences all number	0	0	0	0	0	0	0	2	1	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	1 / 52 (1.92%)	2 / 37 (5.41%)	1 / 39 (2.56%)	1 / 100 (1.00%)	2 / 94 (2.13%)
occurrences all number	0	0	0	0	0	1	2	1	2	2
Oropharyngeal pain
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	1 / 37 (2.70%)	1 / 39 (2.56%)	2 / 100 (2.00%)	1 / 94 (1.06%)
occurrences all number	0	0	0	0	1	0	1	2	2	1
Atelectasis
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Diaphragmatic paralysis
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Hypoxia
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	4 / 100 (4.00%)	0 / 55 (0.00%)	9 / 102 (8.82%)	5 / 100 (5.00%)	1 / 20 (5.00%)	1 / 52 (1.92%)	1 / 37 (2.70%)	2 / 39 (5.13%)	1 / 100 (1.00%)	4 / 94 (4.26%)
occurrences all number	4	0	9	6	1	1	1	2	1	5
Depression
subjects affected / exposed	1 / 100 (1.00%)	3 / 55 (5.45%)	3 / 102 (2.94%)	3 / 100 (3.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	2 / 37 (5.41%)	0 / 39 (0.00%)	2 / 100 (2.00%)	4 / 94 (4.26%)
occurrences all number	1	3	3	3	1	0	2	0	2	5
Insomnia
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	3 / 52 (5.77%)	4 / 37 (10.81%)	2 / 39 (5.13%)	2 / 100 (2.00%)	2 / 94 (2.13%)
occurrences all number	0	0	0	0	0	3	4	2	2	2
Investigations
Blood cholesterol increased
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Blood glucose increased
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	1 / 100 (1.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0
Transaminases increased
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	5 / 100 (5.00%)	5 / 55 (9.09%)	6 / 102 (5.88%)	14 / 100 (14.00%)	2 / 20 (10.00%)	10 / 52 (19.23%)	2 / 37 (5.41%)	3 / 39 (7.69%)	16 / 100 (16.00%)	16 / 94 (17.02%)
occurrences all number	7	13	6	16	3	12	4	4	21	19
Skin laceration
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	3 / 52 (5.77%)	0 / 37 (0.00%)	0 / 39 (0.00%)	1 / 100 (1.00%)	1 / 94 (1.06%)
occurrences all number	0	0	0	0	1	5	0	0	1	1
Ligament rupture
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Procedural pain
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	2 / 20 (10.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences all number	0	0	0	0	2	0	0	0	0	1
Cardiac disorders
Ventricular extrasystoles
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	3 / 100 (3.00%)	4 / 55 (7.27%)	9 / 102 (8.82%)	6 / 100 (6.00%)	0 / 20 (0.00%)	1 / 52 (1.92%)	2 / 37 (5.41%)	2 / 39 (5.13%)	4 / 100 (4.00%)	4 / 94 (4.26%)
occurrences all number	3	4	10	7	0	1	2	2	4	4
Headache
subjects affected / exposed	18 / 100 (18.00%)	6 / 55 (10.91%)	19 / 102 (18.63%)	21 / 100 (21.00%)	3 / 20 (15.00%)	1 / 52 (1.92%)	5 / 37 (13.51%)	5 / 39 (12.82%)	7 / 100 (7.00%)	12 / 94 (12.77%)
occurrences all number	37	8	43	25	3	2	9	15	14	13
Parkinson's disease
subjects affected / exposed	1 / 100 (1.00%)	4 / 55 (7.27%)	9 / 102 (8.82%)	8 / 100 (8.00%)	1 / 20 (5.00%)	1 / 52 (1.92%)	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	1	4	9	9	1	2	1	0	0	0
Paraesthesia
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	1 / 100 (1.00%)	2 / 94 (2.13%)
occurrences all number	0	0	0	0	1	0	0	0	1	2
Restless legs syndrome
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Somnolence
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	1 / 39 (2.56%)	1 / 100 (1.00%)	1 / 94 (1.06%)
occurrences all number	0	0	0	0	1	0	0	1	1	1
Transient ischaemic attack
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences all number	0	0	0	0	1	0	2	0	0	1
Coagulopathy
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Ear and labyrinth disorders
Paraesthesia ear
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Vertigo
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	1 / 100 (1.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	1	0
Gastrointestinal disorders
Constipation
subjects affected / exposed	5 / 100 (5.00%)	3 / 55 (5.45%)	5 / 102 (4.90%)	6 / 100 (6.00%)	1 / 20 (5.00%)	1 / 52 (1.92%)	2 / 37 (5.41%)	1 / 39 (2.56%)	4 / 100 (4.00%)	7 / 94 (7.45%)
occurrences all number	5	3	5	6	2	1	2	1	4	7
Diarrhoea
subjects affected / exposed	4 / 100 (4.00%)	5 / 55 (9.09%)	5 / 102 (4.90%)	6 / 100 (6.00%)	1 / 20 (5.00%)	1 / 52 (1.92%)	0 / 37 (0.00%)	0 / 39 (0.00%)	2 / 100 (2.00%)	3 / 94 (3.19%)
occurrences all number	4	7	6	9	1	1	0	0	3	3
Nausea
subjects affected / exposed	6 / 100 (6.00%)	1 / 55 (1.82%)	6 / 102 (5.88%)	6 / 100 (6.00%)	1 / 20 (5.00%)	2 / 52 (3.85%)	2 / 37 (5.41%)	4 / 39 (10.26%)	4 / 100 (4.00%)	7 / 94 (7.45%)
occurrences all number	10	1	9	7	1	4	4	5	5	11
Dysphagia
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	1 / 39 (2.56%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences all number	0	0	0	0	1	0	0	1	0	1
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	1 / 39 (2.56%)	2 / 100 (2.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	2	0
Haemorrhoids
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences all number	0	0	0	0	1	0	1	0	0	1
Toothache
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	1 / 52 (1.92%)	0 / 37 (0.00%)	2 / 39 (5.13%)	0 / 100 (0.00%)	3 / 94 (3.19%)
occurrences all number	0	0	0	0	0	1	0	2	0	4
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	3 / 100 (3.00%)	1 / 55 (1.82%)	0 / 102 (0.00%)	5 / 100 (5.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	3 / 39 (7.69%)	0 / 100 (0.00%)	2 / 94 (2.13%)
occurrences all number	4	1	0	5	0	0	0	3	0	2
Skin irritation
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Skin ulcer
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	7 / 100 (7.00%)	5 / 55 (9.09%)	9 / 102 (8.82%)	11 / 100 (11.00%)	1 / 20 (5.00%)	3 / 52 (5.77%)	4 / 37 (10.81%)	3 / 39 (7.69%)	7 / 100 (7.00%)	2 / 94 (2.13%)
occurrences all number	10	8	12	11	1	3	5	4	8	2
Back pain
subjects affected / exposed	8 / 100 (8.00%)	3 / 55 (5.45%)	8 / 102 (7.84%)	13 / 100 (13.00%)	0 / 20 (0.00%)	5 / 52 (9.62%)	4 / 37 (10.81%)	6 / 39 (15.38%)	5 / 100 (5.00%)	8 / 94 (8.51%)
occurrences all number	11	4	15	15	0	5	4	6	12	10
Musculoskeletal stiffness
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0
Pain in extremity
subjects affected / exposed	2 / 100 (2.00%)	4 / 55 (7.27%)	5 / 102 (4.90%)	1 / 100 (1.00%)	0 / 20 (0.00%)	2 / 52 (3.85%)	1 / 37 (2.70%)	2 / 39 (5.13%)	2 / 100 (2.00%)	2 / 94 (2.13%)
occurrences all number	2	4	6	1	0	2	1	2	3	2
Infections and infestations
Covid-19
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	2 / 37 (5.41%)	2 / 39 (5.13%)	6 / 100 (6.00%)	3 / 94 (3.19%)
occurrences all number	0	0	0	0	0	0	2	2	6	3
Influenza
subjects affected / exposed	3 / 100 (3.00%)	1 / 55 (1.82%)	7 / 102 (6.86%)	1 / 100 (1.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	3	1	9	1	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	12 / 100 (12.00%)	10 / 55 (18.18%)	10 / 102 (9.80%)	13 / 100 (13.00%)	2 / 20 (10.00%)	2 / 52 (3.85%)	0 / 37 (0.00%)	0 / 39 (0.00%)	4 / 100 (4.00%)	5 / 94 (5.32%)
occurrences all number	13	13	12	14	2	2	0	0	4	5
Upper respiratory tract infection
subjects affected / exposed	3 / 100 (3.00%)	2 / 55 (3.64%)	6 / 102 (5.88%)	7 / 100 (7.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	5	2	7	11	0	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	2 / 20 (10.00%)	3 / 52 (5.77%)	2 / 37 (5.41%)	1 / 39 (2.56%)	2 / 100 (2.00%)	2 / 94 (2.13%)
occurrences all number	0	0	0	0	2	3	3	1	2	4
Bronchitis
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	0 / 20 (0.00%)	0 / 52 (0.00%)	2 / 37 (5.41%)	0 / 39 (0.00%)	0 / 100 (0.00%)	1 / 94 (1.06%)
occurrences all number	0	0	0	0	0	0	2	0	0	1
Tooth infection
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	1 / 52 (1.92%)	0 / 37 (0.00%)	0 / 39 (0.00%)	1 / 100 (1.00%)	1 / 94 (1.06%)
occurrences all number	0	0	0	0	1	1	0	0	1	1
Metabolism and nutrition disorders
Calcium deficiency
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Decreased appetite
subjects affected / exposed	0 / 100 (0.00%)	0 / 55 (0.00%)	0 / 102 (0.00%)	0 / 100 (0.00%)	1 / 20 (5.00%)	0 / 52 (0.00%)	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 100 (0.00%)	0 / 94 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

09 Aug 2017

- Reduced the length of the treatment period and total duration of subject participation in the study. - Increased the number of subjects in the study and updated the sample size considerations supporting that change. - Modified inclusion criteria to reduce the time from past diagnosis with PD, to clarify clinical presentation details, and to indicate that subjects with Lewy body dementia would not be included in the study. - Modified inclusion criteria to lengthen the washout duration for levodopa treatment before entry into the study from 4 weeks to 12 weeks, to describe PD medications excluded, and to shorten the maximum duration of allowed prior PD treatment regimens from 3 months to 30 days. - Changed the dose levels from 3 mg/kg, 15 mg/kg, and 45 mg/kg (dosing based on body weight) to 250 mg, 1250 mg, and 3500 mg (fixed dosing) for both cohorts.

22 Oct 2017

Added a 1-year active-treatment dose-blinded period, extending the total study treatment period to 2 years.

15 Aug 2018

Added retesting and rescreening flexibility for subjects with nonclinically significant out-of-range laboratory results as well as those who cannot complete the Day 1 visit within the designated screening period.

12 Feb 2019

Extended the screening period by 1 week (7 days).

11 Jul 2019

Extended the active treatment dose-blinded period from Year 2 into Years 3 and 4. Dosing would end when the last subject has received the last dose in Year 2 (at Week 96), and the study would end when the last subject has had the Final Visit in Year 2 (12 weeks after the last dose [Week 108 visit]).

03 Feb 2020

Specified the timing of DaT/SPECT scans for certain subjects, as requested by the German Radiology Authority.

11 Aug 2020

This amendment was for 2 primary reasons: the addition of remote visits to ease the conduct of the study during any public health emergency and changes to the study objectives and endpoints to increase the scientific value of the study as detailed below. 1. Added the use of remote visits 2. Modified the study objectives and endpoints as follows: - Primary objective and endpoints: - Upgraded the evaluation of clinical efficacy of BIIB054 via MDS-UPDRS Total Score from an exploratory to primary objective along with its associated endpoints - Updated the objective to clearly state that the clinical efficacy of BIIB054 will be assessed via dose response using the change from baseline in MDS-UPDRS Total Score - Added the change from baseline to Week 72 evaluation to the primary endpoint - Moved the current primary objective and endpoint related to safety from primary to secondary objective and endpoint. - Added the following objects and/or endpoints and/or evaluation timepoints: - Added the secondary objective and endpoint: To evaluate the clinical efficacy of BIIB054 via MDS-UPDRS Total Score as measured by the change from baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at end of study - Added the secondary endpoint: Change from baseline to Week 52, Week 72, and end of study in MDS-UPDRS of Subparts I, II, and III (each part separately) -Removed the delineation between Year 1 (Placebo-Controlled Portion of the Study)

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.

The study did not meet its primary endpoint for year 1 and failed to meet secondary endpoints resulting in the development of BIIB054 for Parkinson's disease to be discontinued and SPARK study was closed.

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Clinical trials

Clinical Trial Results: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study, with an Active-Treatment Dose-Blinded Period, to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Subjects with Parkinson’s Disease

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52

Primary: Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52

Primary: Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 72

Primary: Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 72

Secondary: Percentage of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Percentage of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96

Secondary: Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96

Secondary: Serum Concentration of BIIB054

Secondary: Serum Concentration of BIIB054

Secondary: Change From Baseline in MDS-UPDRS Subpart I Score at Week 52

Secondary: Change From Baseline in MDS-UPDRS Subpart I Score at Week 52

Secondary: Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96

Secondary: Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96

Secondary: Change From Baseline in MDS-UPDRS Subpart II Score at Week 52

Secondary: Change From Baseline in MDS-UPDRS Subpart II Score at Week 52

Secondary: Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96

Secondary: Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96

Secondary: Change From Baseline in MDS-UPDRS Subpart III Score at Week 52

Secondary: Change From Baseline in MDS-UPDRS Subpart III Score at Week 52

Secondary: Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96

Secondary: Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96

Secondary: Change From Baseline in Striatal Binding Ratio (SBR) in the Putamen as Measured by Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter (DaT) at Week 52

Secondary: Change From Baseline in Striatal Binding Ratio (SBR) in the Putamen as Measured by Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter (DaT) at Week 52

Secondary: Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52

Secondary: Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52

Secondary: Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52

Secondary: Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52

Secondary: Percentage of Subjects With Anti-BIIB054 Antibodies in the Serum

Secondary: Percentage of Subjects With Anti-BIIB054 Antibodies in the Serum

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study, with an Active-Treatment Dose-Blinded Period, to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Subjects with Parkinson’s Disease