SPARK: Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Participants With Parkinson's Disease

Sponsor

Biogen (Industry)

Overall Status

Terminated

CT.gov ID

NCT03318523

Collaborator

(none)

357

Enrollment

Locations

Arms

39.6

Actual Duration (Months)

4.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: Placebo Drug: BIIB054	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

357 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 10, 2018

Actual Primary Completion Date :

Oct 26, 2020

Actual Study Completion Date :

Apr 29, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Year 1: Participants will receive matching placebo to BIIB054 on Day 1 and then every 4 weeks. Year 2: Participants who received placebo in year 1 will be randomized into one of the active treatment arms in year 2 and will receive BIIB054 intravenous (IV) infusion on Week 52 and then every 4 weeks.	Drug: Placebo Administered as specified in the treatment arm
Experimental: BIIB054 250 mg Participants will receive BIIB054 250 milligrams (mg) intravenous (IV) infusion on Day 1 and then every 4 weeks.	Drug: BIIB054 Administered as specified in the treatment arm.
Experimental: BIIB054 1250 mg Participants will receive BIIB054 1250 mg IV infusion on Day 1 and then every 4 weeks.	Drug: BIIB054 Administered as specified in the treatment arm.
Experimental: BIIB054 3500 mg Participants will receive BIIB054 3500 mg IV infusion on Day 1 and then every 4 weeks.	Drug: BIIB054 Administered as specified in the treatment arm.

Outcome Measures

Primary Outcome Measures

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 [Baseline, Week 52]
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 participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. 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. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
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 [Baseline, Week 72]
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 participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. 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. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.

Secondary Outcome Measures

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to 3 years]
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the participant at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event.
Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96 [Baseline, Week 96]
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 participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. 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. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Serum Concentration of BIIB054 [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]
Change From Baseline in MDS-UPDRS Subpart I Score at Week 52 [Baseline, Week 52]
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 participant (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 mean values reported are the adjusted mean values.
Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96 [Baseline, Weeks 72 and 96]
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 participant (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 mean values reported are the adjusted mean values.
Change From Baseline in MDS-UPDRS Subpart II Score at Week 52 [Baseline, Week 52]
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 participant. 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 mean values reported are the adjusted mean values.
Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96 [Baseline, Weeks 72 and 96]
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 participant. 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 mean values reported are the adjusted mean values.
Change From Baseline in MDS-UPDRS Subpart III Score at Week 52 [Baseline, Week 52]
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 mean values reported are the adjusted mean values.
Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96 [Baseline, Weeks 72 and 96]
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 mean values reported are the adjusted mean values.
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 [Baseline, Week 52]
SBR in the putamen as measured by SPECT imaging of the dopamine transporter (DaT) with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.
Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52 [Baseline, Week 52]
SBR in the striatum as measured by SPECT imaging of the DaT with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.
Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52 [Baseline, Week 52]
SBR in the caudate as measured by SPECT imaging of the DaT with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.
Percentage of Participants With Anti-BIIB054 Antibodies in the Serum [Up to Week 144]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Diagnosed with Parkinson's disease (PD) within a maximum of 3 years prior to Screening.
Score of ≤2.5 on the Modified Hoehn and Yahr Scale.
Has not received any medication for the treatment of the motor symptoms of PD for at least 12 weeks prior to Day 1 and, in the opinion of the Investigator, is not expected to require PD treatment for at least 6 months following Day 1. Maximum total duration of prior PD regimens should not exceed 30 days. Stable (at least 8 weeks) dosages of medications that are used to treat conditions other than PD tremor are allowed. Further guidance will be provided by the study's Medical Monitor on a case by case basis.
Screening dopamine transporter (DaT)/ single-photon emission computed tomography (SPECT) results consistent with neurodegenerative Parkinsonism (central reading).
All women of childbearing potential and all men must practice highly effective contraception during the study and for 6 months after their last dose of study treatment.

Exclusion Criteria:

Presence of freezing of gait.
Montreal cognitive assessment (MOCA) score <23 or other significant cognitive impairment or clinical dementia that, in the opinion of the Investigator, would interfere with study evaluation.
History of or screening brain magnetic resonance imaging (MRI) scan indicative of clinically significant abnormality, as read by central reader.
History of severe allergic or anaphylactic reactions, or history of hypersensitivity to BIIB054 or any of the inactive ingredients in the drug product or to radioligands or iodine used in the study.
Participation in any active immunotherapy study targeting alpha-synuclein.
Use of allowed medications not previously specified at doses that have not been stable for at least 8 weeks before Day 1, and/or that are not expected to remain stable for the duration of the study.
Clinically significant abnormal laboratory test values at Screening, as determined by the Investigator.
Blood donation (1 unit or more) within 8 weeks before Day 1 (must also refrain from donating blood for the duration of the study).

NOTE : Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	St. Joseph's Hopsital & Medical Center- Barrow Neurological Institute	Phoenix	Arizona	United States	85013
3	Research Site	La Jolla	California	United States	92093-0886
4	Cedars Sinai	Los Angeles	California	United States	90048
5	University of California San Francisco Medical Center	San Francisco	California	United States	94158
6	Research Site	Stanford	California	United States	94305
7	University of Colorado Health	Aurora	Colorado	United States	80045
8	Rocky Mountain Movement Disorders Center, PC	Englewood	Colorado	United States	80113
9	Parkinson's Disease and Movement Disorders Centerf	Boca Raton	Florida	United States	33486
10	Mayo Clinic Hospital	Jacksonville	Florida	United States	32224
11	Bioclinica Research	Orlando	Florida	United States	32806
12	USF Health Byrd Institute	Tampa	Florida	United States	33616
13	Northwestern University PD and Movement Disorders Center	Chicago	Illinois	United States	60611
14	Research Site	Chicago	Illinois	United States	60612
15	University of Kansas Medical Center Research Institute	Kansas City	Kansas	United States	66160
16	Ochsner Health System	New Orleans	Louisiana	United States	70121
17	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
18	Boston University Medical Center	Boston	Massachusetts	United States	02118
19	Quest Research Institute	Farmington Hills	Michigan	United States	48334
20	NYU Langone Health Center	New York	New York	United States	10017
21	Research Site	New York	New York	United States	10032
22	Research Site	Durham	North Carolina	United States	27705
23	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
24	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44106
25	Research Site	Philadelphia	Pennsylvania	United States	19107
26	University of Pittsburgh Medical Center Health System	Pittsburgh	Pennsylvania	United States	15213
27	Medical University of South Carolina	Charleston	South Carolina	United States	29425
28	Research Site	Nashville	Tennessee	United States	37232
29	Research Site	Houston	Texas	United States	77030
30	Booth Gardner Parkinson's Care Center at Evergreen Health	Kirkland	Washington	United States	98034
31	Inland Northwest Research	Spokane	Washington	United States	99204
32	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
33	Research Site	Innsbruck		Austria	6020
34	University Health Network	Toronto	Ontario	Canada	M5T 2S8
35	Montreal Neurological Institute Clinical Research Unit	Montréal	Quebec	Canada	H3A 2B4
36	Research Name	Toulouse Cedex 09	Haute Garonne	France	31059
37	CHU Nantes - Hopital Nord Laënnec	Nantes	Loire Atlantique	France	44093
38	Hopital Roger Salengro - CHU Lille	Lille Cedex	Nord	France	59037
39	Hôpital Henri Mondor	Créteil	Val De Marne	France	94010
40	Research Site	Paris		France	75013
41	Universitaetsklinikum Ulm	Ulm	Baden Wuerttemberg	Germany	89081
42	Klinikum rechts der Isar der TU Muenchen	Muenchen	Bayern	Germany	81675
43	Universitaetsklinikum Wuerzburg	Wuerzburg	Bayern	Germany	97080
44	Paracelsus-Elena-Klinik	Kassel	Hessen	Germany	34128
45	Universitaetsklinikum Aachen AOeR	Aachen	Nordrhein Westfalen	Germany	52074
46	Research Site	Bochum	Nordrhein Westfalen	Germany	44791
47	Research Site	Haifa		Israel	3109601
48	Research Site	Tel Aviv		Israel	6423906
49	I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo	Pozzilli	Isernia	Italy	86077
50	Ospedale Bellaria	Bologna		Italy	40139
51	Azienda Ospedaliero Univ. Policlinico Gaspare Rodolico	Catania		Italy	95125
52	Research Site	Milano		Italy	20122
53	Ospedale San Raffaele	Milano		Italy	20132
54	Research Site	Milano		Italy	20132
55	Seconda Università degli Studi di Napoli	Napoli		Italy	80138
56	Research Site	Pisa		Italy	56126
57	IRCCS San Raffaele	Roma		Italy	00163
58	Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona	Salerno		Italy	84131
59	Azienda Ospedaliera Santa Maria di Terni	Terni		Italy	05100
60	Hospital General de Catalunya	Sant Cugat del Vallés	Barcelona	Spain	08190
61	Research Site	Móstoles	Madrid	Spain	28938
62	Clinica Universidad de Navarra	Pamplona	Navarra	Spain	31008
63	Biocruces Health Research Institute	Barakaldo	Vizcaya	Spain	48903
64	Hospital Clinic De Barcalona	Barcelona		Spain	08036
65	Hospital Santa Creu i Sant Pau	Barcelona		Spain	08041
66	Research Site	Madrid		Spain	28006
67	Research Site	Madrid		Spain	28007
68	Research Site	Madrid		Spain	28034
69	Research Site	Sevilla		Spain	41013
70	Research Site	Cambridge	Cambridgeshire	United Kingdom	CB2 0QQ
71	Salford Royal	Salford	Greater Manchester	United Kingdom	M6 8HD
72	Research Site	Oxford	Oxfordshire	United Kingdom	OX3 9DU
73	Clinical Ageing Research Unit	Newcastle upon Tyne	Tyne & Wear	United Kingdom	NE4 5PL
74	Royal Hallamshire Hospital	Sheffield	West Midlands	United Kingdom	S10 2JF
75	Research Site	London		United Kingdom	WC1N 3BG

Sponsors and Collaborators

Biogen

Investigators

Study Director: Medical Director, Biogen

Study Documents (Full-Text)

More Information

Additional Information:

Fox Trial Finder

Publications

None provided.

Responsible Party:

Biogen

ClinicalTrials.gov Identifier:

NCT03318523

Other Study ID Numbers:

228PD201
2016-004610-95

First Posted:

Oct 24, 2017

Last Update Posted:

Feb 28, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Biogen

BIIB054

Alpha-synuclein

Additional relevant MeSH terms:

Parkinson Disease

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at 75 investigational sites from 10 January 2018 to 29 April 2021.
Pre-assignment Detail	Participants with Parkinson's Disease (PD) were enrolled and randomized to receive placebo or BIIB054 250/1250/3500 milligrams (mg) for Year 1 in Placebo-Controlled (PC) Period. Following Year 1, participants on placebo (delayed start) were re-randomized to receive BIIB054 250/1250/3500 mg dose, and others on BIIB054 in Year 1 continued to receive the same dose until their Week 96 visit.

Arm/Group Title	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: Placebo to BIIB054 1250 mg (Delayed Start)	DBE Period: Placebo to BIIB054 3500 mg (Delayed Start)	DBE Period: BIIB054 250 mg (Early Start)	DBE Period: BIIB054 1250 mg (Early Start)	DBE Period: BIIB054 3500 mg (Early Start)
Arm/Group Description	Participants received BIIB054-matching placebo, intravenous (IV) infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054 250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received placebo in the PC period were included in this arm.	Participants received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received placebo in the PC period were included in this arm.	Participants received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received placebo in the PC period were included in this arm.	Participants received BIIB054 250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received BIIB054 250 mg in the PC period were included in this arm.	Participants received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received BIIB054 1250 mg in the PC period were included in this arm.	Participants received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received BIIB054 3500 mg in the PC period were included in this arm.
Period Title: PC Period: Up to Year 1
STARTED	100	55	102	100	0	0	0	0	0	0
COMPLETED	96	53	100	96	0	0	0	0	0	0
NOT COMPLETED	4	2	2	4	0	0	0	0	0	0
Period Title: PC Period: Up to Year 1
STARTED	0	0	0	0	20	37	39	52	100	96
Number of Participants Dosed	0	0	0	0	20	37	39	52	100	94
COMPLETED	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	20	37	39	52	100	96

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	Participants received BIIB054-matching placebo, intravenous (IV) infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Total of all reporting groups
Overall Participants	100	55	102	100	357
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.0 (8.39)	61.3 (9.24)	59.2 (8.48)	59.3 (9.92)	60.1 (9.01)
Sex: Female, Male (Count of Participants)
Female	28 28%	16 29.1%	29 28.4%	34 34%	107 30%
Male	72 72%	39 70.9%	73 71.6%	66 66%	250 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 3%	1 1.8%	1 1%	6 6%	11 3.1%
Not Hispanic or Latino	96 96%	54 98.2%	101 99%	94 94%	345 96.6%
Unknown or Not Reported	1 1%	0 0%	0 0%	0 0%	1 0.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	2 2%	2 0.6%
Asian	0 0%	0 0%	3 2.9%	3 3%	6 1.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	1 1%	0 0%	1 0.3%
White	96 96%	53 96.4%	92 90.2%	84 84%	325 91%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	4 4%	2 3.6%	6 5.9%	11 11%	23 6.4%
Baseline Movement Disorder Society Sponsored Revision of the Unified PD Rating Scale Total Score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	31.9 (12.41)	31.9 (12.25)	32.9 (12.58)	32.6 (13.46)	32.4 (12.69)
Baseline MDS-UPDRS Subpart I Score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	4.3 (3.50)	3.3 (2.74)	4.8 (3.99)	4.3 (3.60)	4.3 (3.59)
Baseline MDS-UPDRS Subpart II Score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	5.4 (3.87)	5.0 (3.30)	5.3 (3.66)	5.5 (4.30)	5.3 (3.84)
Baseline MDS-UPDRS Subpart III Score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	22.2 (9.31)	23.5 (9.38)	22.8 (8.69)	22.9 (8.86)	22.8 (8.99)
Baseline Total Striatum Striatal Binding Ratio (SBR) (striatal binding ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [striatal binding ratio]	1.295 (0.3177)	1.409 (0.3875)	1.342 (0.3197)	1.351 (0.3495)	1.342 (0.3393)
Baseline Total Putamen SBR (striatal binding ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [striatal binding ratio]	1.255 (0.3429)	1.388 (0.4294)	1.291 (0.3269)	1.286 (0.3627)	1.295 (0.3597)
Baseline Total Caudate SBR (striatal binding ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [striatal binding ratio]	1.336 (0.3279)	1.433 (0.3751)	1.397 (0.3417)	1.416 (0.3643)	1.391 (0.3501)

Outcome Measures

1. Primary Outcome

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
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 participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. 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. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). Number of participants analyzed were participants analyzed for this outcome measure.

Arm/Group Title	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Arm/Group Description	Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	53	29	57	51
Mean (Standard Error) [score on a scale]	10.78 (1.490)	10.48 (1.951)	11.29 (1.446)	10.86 (1.518)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments	Change From Baseline in MDS-UPDRS Total Score at Week 52
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.8976
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95% -4.888 to 4.287
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments	Change From Baseline in MDS-UPDRS Total Score at Week 52
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.7960
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95% -3.310 to 4.312
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments	Change From Baseline in MDS-UPDRS Total Score at Week 52
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.9695
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95% -3.805 to 3.956
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

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
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 participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. 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. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Time Frame	Baseline, Week 72

Outcome Measure Data

Analysis Population Description
The ITT population was defined as all randomized participants 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 outcome measure. Number of participants analyzed were participants analyzed for this outcome measure.

Arm/Group Title	PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Arm/Group Description	Participants 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.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	68	32	62	64
Mean (Standard Error) [score on a scale]	7.11 (1.476)	6.83 (2.032)	8.66 (1.496)	6.94 (1.508)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments	Change From Baseline in MDS-UPDRS Total Score at Week 72
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.9093
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95% -5.035 to 4.483
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments	Change From Baseline in MDS-UPDRS Total Score at Week 72
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.4327
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95% -2.336 to 5.440
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments	Change From Baseline in MDS-UPDRS Total Score at Week 72
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.9330
	Comments
	Method	Mixed Model with repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95% -4.051 to 3.719
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the participant at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description
The safety population was defined as all participants who received at least one dose of study treatment (BIIB054).

Arm/Group Title	PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Arm/Group Description	Participants 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.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	96	55	102	100
AEs	77.1 77.1%	85.5 155.5%	89.2 87.5%	93.0 93%
SAEs	8.3 8.3%	10.9 19.8%	8.8 8.6%	12.0 12%

4. Secondary Outcome

Title	Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96
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 participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. 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. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Time Frame	Baseline, Week 96

Outcome Measure Data

Analysis Population Description
The ITT population was defined as all randomized participants 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 outcome measure. Number of participants analyzed were participants analyzed for this outcome measure.

Arm/Group Title	PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Arm/Group Description	Participants 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.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	67	28	62	59
Mean (Standard Error) [score on a scale]	7.88 (1.616)	8.28 (2.317)	8.71 (1.628)	8.87 (1.659)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.8828
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.41
	Confidence Interval	(2-Sided) 95% -5.013 to 5.825
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.7019
	Comments
	Method	Mixed Model for Repeated Measure
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95% -3.458 to 5.128
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.6519
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95% -3.323 to 5.301
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Serum Concentration of BIIB054
Description
Time Frame	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

Outcome Measure Data

Analysis Population Description
The pharmacokinetic (PK) population was defined as all participants in the ITT population who had at least one measurable BIIB054 concentration in serum or cerebrospinal fluid (CSF). Number analyzed is the number of participants analyzed at the specified time point.

Arm/Group Title	BIIB054 250 mg	BIIB054 1250 mg	BIIB054 3500 mg
Arm/Group Description	Participants received BIIB054, 250 mg, IV infusion, from Day 1 up to EOS (approximately 3 years).	Participants received BIIB054, 1250 mg, IV infusion, from Day 1 up to EOS (approximately 3 years).	Participants received BIIB054, 3500 mg, IV infusion, from Day 1 up to EOS (approximately 3 years).
Measure Participants	75	139	139
Baseline (Pre-dose)	0.00 (0.000)	7.47 (51.281)	0.01 (0.065)
Baseline (1 Hour Post-dose)	75.02 (15.829)	374.79 (86.004)	1137.28 (335.336)
Week 4 (Pre-dose)	20.37 (5.004)	95.36 (27.882)	306.20 (95.257)
Week 4 (1 Hour Post-dose)	97.09 (19.711)	468.56 (190.589)	1354.19 (364.468)
Week 8 (Pre-dose)	29.73 (8.371)	169.79 (68.025)	495.79 (153.357)
Week 8 (1 Hour Post-dose)	103.69 (26.964)	543.91 (143.212)	1591.57 (465.798)
Week 12 (Pre-dose)	36.76 (11.830)	195.16 (51.020)	580.43 (185.761)
Week 12 (1 Hour Post-dose)	112.61 (27.378)	569.41 (141.250)	1632.29 (459.839)
Week 16 (Pre-dose)	40.82 (11.421)	201.33 (73.451)	642.06 (194.288)
Week 16 (1 Hour Post-dose)	117.08 (27.401)	614.85 (186.892)	1739.98 (506.346)
Week 24 (Pre-dose)	43.31 (12.906)	235.69 (84.454)	724.60 (228.295)
Week 24 (1 Hour Post-dose)	125.79 (36.695)	664.26 (209.251)	1867.92 (470.283)
Week 32 (Pre-dose)	42.69 (13.486)	260.35 (104.397)	772.75 (299.703)
Week 32 (1 Hour Post-dose)	139.00 (34.758)	626.16 (164.497)	1985.71 (497.545)
Week 36 (Pre-dose)	45.77 (11.867)	262.80 (85.052)	819.83 (328.774)
Week 36 (1 Hour Post-dose)	123.67 (29.536)	665.60 (145.235)	1916.84 (543.373)
Week 44 (Pre-dose)	58.17 (22.774)	280.40 (116.590)	858.43 (349.573)
Week 44 (1 Hour Post-dose)	143.33 (41.004)	582.40 (194.431)	2066.25 (579.555)
Week 52 (Pre-dose)	46.70 (19.343)	232.08 (87.529)	787.35 (341.229)
Week 52 (1 Hour Post-dose)	114.59 (25.913)	645.36 (264.270)	1920.78 (479.511)
Week 60 (Pre-dose)	43.41 (15.973)	254.52 (88.446)	724.77 (314.854)
Week 60 (1 Hour Post-dose)	122.55 (29.374)	657.94 (149.654)	1905.43 (494.136)
Week 68 (Pre-dose)	706.25 (966.969)	202.33 (34.210)	1362.50 (533.866)
Week 68 (1 Hour Post-dose)	171.50 (44.548)	576.33 (85.290)	2305.00 (1025.305)
Week 84 (Pre-dose)	47.00 (15.535)	255.54 (81.407)	746.43 (249.770)
Week 84 (1 Hour Post-dose)	134.91 (33.035)	648.62 (120.163)	1942.02 (501.095)
Week 96 (Pre-dose)	41.25 (15.345)	274.56 (71.718)	654.70 (262.926)
Week 96 (1 Hour Post-dose)	122.00 (29.527)	682.30 (123.653)	1822.50 (475.682)
Week 120 (Pre-dose)	34.98 (12.042)	279.00 (99.499)	727.29 (116.793)
Week 120 (1 Hour Post-dose)	119.67 (15.629)	769.83 (279.182)	1717.14 (320.037)
Week 144 (Pre-dose)	365.00 (NA)
Week 144 (1 Hour Post-dose)	721.00 (NA)

6. Secondary Outcome

Title	Change From Baseline in MDS-UPDRS Subpart I Score at Week 52
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 participant (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 mean values reported are the adjusted mean values.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). Number of participants analyzed were participants analyzed for this outcome measure.

Arm/Group Title	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Arm/Group Description	Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	53	29	57	51
Mean (Standard Error) [score on a scale]	1.43 (0.436)	0.90 (0.570)	1.56 (0.423)	1.65 (0.446)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart I Score at Week 52
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.4327
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 95% -1.851 to 0.794
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart I Score at Week 52
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.8155
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95% -0.965 to 1.225
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart I Score at Week 52
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.7015
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95% -0.899 to 1.334
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96
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 participant (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 mean values reported are the adjusted mean values.
Time Frame	Baseline, Weeks 72 and 96

Outcome Measure Data

Analysis Population Description
The ITT population was defined as all randomized participants 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 outcome measure. Number analyzed is the number of participants analyzed at the specified time point.

Arm/Group Title	PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Arm/Group Description	Participants 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.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	100	55	102	100
Change from Baseline at Week 72	1.65 (0.395)	0.61 (0.538)	1.73 (0.402)	1.63 (0.405)
Change from Baseline at Week 96	1.95 (0.398)	1.69 (0.568)	1.93 (0.403)	1.72 (0.414)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart I Score at Week 72
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.1038
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.03
	Confidence Interval	(2-Sided) 95% -2.276 to 0.213
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart I Score at Week 72
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.8689
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95% -0.933 to 1.103
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart I Score at Week 72
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.9820
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95% -1.026 to 1.003
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart I Score at Week 96
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.6930
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.26
	Confidence Interval	(2-Sided) 95% -1.563 to 1.040
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart I Score at Week 96
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.9606
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95% -1.053 to 1.001
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart I Score at Week 96
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.6512
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95% -1.269 to 0.794
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in MDS-UPDRS Subpart II Score at Week 52
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 participant. 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 mean values reported are the adjusted mean values.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). Number of participants analyzed were participants analyzed for this outcome measure.

Arm/Group Title	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Arm/Group Description	Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	54	29	58	51
Mean (Standard Error) [score on a scale]	3.17 (0.473)	2.72 (0.621)	3.16 (0.460)	3.01 (0.486)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart II Score at Week 52
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.5497
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 95% -1.889 to 1.007
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart II Score at Week 52
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.9980
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95% -1.200 to 1.197
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart II Score at Week 52
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.8069
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95% -1.374 to 1.070
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96
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 participant. 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 mean values reported are the adjusted mean values.
Time Frame	Baseline, Weeks 72 and 96

Outcome Measure Data

Analysis Population Description
The ITT population was defined as all randomized participants 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 outcome measure. Number analyzed is the number of participants analyzed at the specified time point.

Arm/Group Title	PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Arm/Group Description	Participants 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.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	100	55	102	100
Change from Baseline at Week 72	1.83 (0.491)	1.62 (0.672)	2.36 (0.497)	1.68 (0.503)
Change from Baseline at Week 96	1.87 (0.529)	1.33 (0.762)	2.39 (0.533)	2.22 (0.541)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart II Score at Week 72
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.7968
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95% -1.786 to 1.372
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart II Score at Week 72
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.4211
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95% -0.766 to 1.827
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart II Score at Week 72
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.8166
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95% -1.448 to 1.143
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart II Score at Week 96
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.5535
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 95% -2.310 to 1.240
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart II Score at Week 96
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.4654
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95% -0.881 to 1.922
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart II Score at Week 96
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.6184
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.36
	Confidence Interval	(2-Sided) 95% -1.051 to 1.763
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in MDS-UPDRS Subpart III Score at Week 52
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 mean values reported are the adjusted mean values.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). Number of participants analyzed were participants analyzed for this outcome measure.

Arm/Group Title	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Arm/Group Description	Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	53	29	58	51
Mean (Standard Error) [score on a scale]	6.10 (1.083)	6.69 (1.419)	6.76 (1.046)	6.20 (1.104)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart III Score at Week 52
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.7274
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95% -2.742 to 3.925
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart III Score at Week 52
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.6385
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95% -2.094 to 3.411
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart III Score at Week 52
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.9467
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95% -2.718 to 2.910
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96
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 mean values reported are the adjusted mean values.
Time Frame	Baseline, Weeks 72 and 96

Outcome Measure Data

Analysis Population Description
The ITT population was defined as all randomized participants 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 outcome measure. Number analyzed is the number of participants analyzed at the specified time point.

Arm/Group Title	PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Arm/Group Description	Participants 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.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	100	55	102	100
Change from Baseline at Week 72	3.64 (1.027)	4.48 (1.404)	4.49 (1.038)	3.69 (1.048)
Change from Baseline at Week 96	4.49 (1.174)	5.14 (1.679)	4.39 (1.180)	5.17 (1.201)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart III Score at Week 72
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.6112
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95% -2.423 to 4.114
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart III Score at Week 72
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.5270
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95% -1.806 to 3.520
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart III Score at Week 72
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.9673
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95% -2.608 to 2.719
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart III Score at Week 96
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.7455
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95% -3.274 to 4.569
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart III Score at Week 96
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.9506
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95% -3.192 to 2.997
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments	Change from Baseline in MDS-UPDRS Subpart III Score at Week 96
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.6643
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95% -2.422 to 3.794
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

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
Description	SBR in the putamen as measured by SPECT imaging of the dopamine transporter (DaT) with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
The pharmacodynamic population was defined as a subset of the ITT population with at least 1 post-baseline pharmacodynamic measurement.

Arm/Group Title	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Arm/Group Description	Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	91	52	97	84
Mean (Standard Error) [striatal binding ratio]	-0.093 (0.0151)	-0.098 (0.0199)	-0.102 (0.0146)	-0.125 (0.0155)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.8274
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.005
	Confidence Interval	(2-Sided) 95% -0.0548 to 0.0438
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.6671
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.009
	Confidence Interval	(2-Sided) 95% -0.0504 to 0.0323
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.1313
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.033
	Confidence Interval	(2-Sided) 95% -0.0751 to 0.0098
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52
Description	SBR in the striatum as measured by SPECT imaging of the DaT with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
The pharmacodynamic population was defined as a subset of the ITT population with at least 1 post-baseline pharmacodynamic measurement.

Arm/Group Title	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Arm/Group Description	Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	91	52	97	84
Mean (Standard Error) [striatal binding ratio]	-0.081 (0.0145)	-0.090 (0.0191)	-0.081 (0.0140)	-0.108 (0.0148)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.7079
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.009
	Confidence Interval	(2-Sided) 95% -0.0562 to 0.0382
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.9835
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.000
	Confidence Interval	(2-Sided) 95% -0.0400 to 0.0392
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.1869
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.027
	Confidence Interval	(2-Sided) 95% -0.0682 to 0.0134
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52
Description	SBR in the caudate as measured by SPECT imaging of the DaT with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
The pharmacodynamic population was defined as a subset of the ITT population with at least 1 post-baseline pharmacodynamic measurement.

Arm/Group Title	PC Period: Placebo	PC Period: BIIB054 250 mg (Early Start)	PC Period: BIIB054 1250 mg (Early Start)	PC Period: BIIB054 3500 mg (Early Start)
Arm/Group Description	Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	91	52	97	84
Mean (Standard Error) [striatal binding ratio]	-0.067 (0.0166)	-0.075 (0.0219)	-0.060 (0.0161)	-0.089 (0.0171)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
	Comments
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.7585
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.008
	Confidence Interval	(2-Sided) 95% -0.0625 to 0.0456
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
	Comments
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.7808
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.006
	Confidence Interval	(2-Sided) 95% -0.0391 to 0.0520
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
	Comments
	Type of Statistical Test	Superiority
	Comments	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.

Statistical Test of Hypothesis	p-Value	0.3532
	Comments
	Method	Mixed Model for Repeated Measures
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.022
	Confidence Interval	(2-Sided) 95% -0.0691 to 0.0248
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Percentage of Participants With Anti-BIIB054 Antibodies in the Serum
Description
Time Frame	Up to Week 144

Outcome Measure Data

Analysis Population Description
The analysis population for immunogenicity was defined as all participants 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 outcome measure.

Arm/Group Title	PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)	PC Period: Early Start BIIB054 250 mg	PC Period: Early Start BIIB054 1250 mg	PC Period: Early Start BIIB054 3500 mg
Arm/Group Description	Participants 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.	Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.	Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.	Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Measure Participants	96	55	100	99
Number [percentage of participants]	0 0%	1.8 3.3%	0 0%	0 0%

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: Placebo to BIIB054 1250 mg (Delayed Start)		DBE Period: Placebo to BIIB054 3500 mg (Delayed Start)		DBE Period: BIIB054 250 mg (Early Start)		DBE Period: BIIB054 1250 mg (Early Start)		DBE Period: BIIB054 3500 mg (Early Start)
Time Frame	Up to 3 years
Adverse Event Reporting Description	Safety Population included all participants who received at least one dose of the study treatment (BIIB054 250 mg, 1250 mg, 3500 mg).

Arm/Group Title	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: Placebo to BIIB054 1250 mg (Delayed Start)		DBE Period: Placebo to BIIB054 3500 mg (Delayed Start)		DBE Period: BIIB054 250 mg (Early Start)		DBE Period: BIIB054 1250 mg (Early Start)		DBE Period: BIIB054 3500 mg (Early Start)
Arm/Group Description	Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.		Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.		Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.		Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.		Participants received BIIB054 250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received placebo in the PC period were included in this arm.		Participants received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received placebo in the PC period were included in this arm.		Participants received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received placebo in the PC period were included in this arm.		Participants received BIIB054 250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received BIIB054 250 mg in the PC period were included in this arm.		Participants received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received BIIB054 1250 mg in the PC period were included in this arm.		Participants received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received BIIB054 3500 mg in the PC period were included in this arm.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
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: Placebo to BIIB054 1250 mg (Delayed Start)		DBE Period: Placebo to BIIB054 3500 mg (Delayed Start)		DBE Period: BIIB054 250 mg (Early Start)		DBE Period: BIIB054 1250 mg (Early Start)		DBE Period: BIIB054 3500 mg (Early Start)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/100 (7%)		4/55 (7.3%)		4/102 (3.9%)		6/100 (6%)		2/20 (10%)		3/37 (8.1%)		3/39 (7.7%)		3/52 (5.8%)		5/100 (5%)		7/94 (7.4%)
Blood and lymphatic system disorders
Monoclonal B-cell lymphocytosis	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Cardiac disorders
Bradycardia	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Myocardial infarction	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Palpitations	0/100 (0%)		0/55 (0%)		0/102 (0%)		1/100 (1%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Pericarditis	0/100 (0%)		0/55 (0%)		1/102 (1%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Sinus bradycardia	0/100 (0%)		1/55 (1.8%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Gastrointestinal disorders
Small intestinal obstruction	1/100 (1%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
General disorders
Impaired healing	0/100 (0%)		0/55 (0%)		0/102 (0%)		1/100 (1%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Hepatobiliary disorders
Hepatitis toxic	1/100 (1%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Immune system disorders
Anaphylactic reaction	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		1/37 (2.7%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Infections and infestations
COVID-19	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		1/37 (2.7%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
COVID-19 pneumonia	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		1/37 (2.7%)		0/39 (0%)		0/52 (0%)		1/100 (1%)		0/94 (0%)
Gastroenteritis	1/100 (1%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Gastroenteritis viral	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		1/100 (1%)		0/94 (0%)
Perirectal abscess	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Viral infection	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Injury, poisoning and procedural complications
Arthropod sting	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		1/37 (2.7%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Fall	0/100 (0%)		0/55 (0%)		0/102 (0%)		1/100 (1%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		1/52 (1.9%)		0/100 (0%)		0/94 (0%)
Femur fracture	0/100 (0%)		0/55 (0%)		0/102 (0%)		1/100 (1%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Jaw fracture	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		1/52 (1.9%)		0/100 (0%)		0/94 (0%)
Muscle strain	1/100 (1%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Pelvic fracture	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Post lumbar puncture syndrome	1/100 (1%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Road traffic accident	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Spinal compression fracture	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Ulna fracture	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Musculoskeletal and connective tissue disorders
Arthritis	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Back pain	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Lumbar spinal stenosis	0/100 (0%)		1/55 (1.8%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Musculoskeletal chest pain	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Osteoarthritis	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		1/39 (2.6%)		0/52 (0%)		1/100 (1%)		0/94 (0%)
Rotator cuff syndrome	0/100 (0%)		0/55 (0%)		1/102 (1%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		1/52 (1.9%)		0/100 (0%)		0/94 (0%)
Spinal stenosis	0/100 (0%)		1/55 (1.8%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Spondylolisthesis	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		1/39 (2.6%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		1/100 (1%)		0/94 (0%)
Glioblastoma	0/100 (0%)		0/55 (0%)		0/102 (0%)		1/100 (1%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Invasive lobular breast carcinoma	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		1/37 (2.7%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Prostate cancer	0/100 (0%)		1/55 (1.8%)		0/102 (0%)		1/100 (1%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Nervous system disorders
Intracranial mass	0/100 (0%)		0/55 (0%)		0/102 (0%)		1/100 (1%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Sciatica	1/100 (1%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Transient ischaemic attack	0/100 (0%)		0/55 (0%)		0/102 (0%)		1/100 (1%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		1/52 (1.9%)		1/100 (1%)		0/94 (0%)
Psychiatric disorders
Depression	0/100 (0%)		0/55 (0%)		0/102 (0%)		1/100 (1%)		0/20 (0%)		0/37 (0%)		1/39 (2.6%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Suicidal ideation	0/100 (0%)		0/55 (0%)		1/102 (1%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Renal and urinary disorders
Nephrolithiasis	0/100 (0%)		0/55 (0%)		1/102 (1%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/100 (1%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/100 (1%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Other (Not Including 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: Placebo to BIIB054 1250 mg (Delayed Start)		DBE Period: Placebo to BIIB054 3500 mg (Delayed Start)		DBE Period: BIIB054 250 mg (Early Start)		DBE Period: BIIB054 1250 mg (Early Start)		DBE Period: BIIB054 3500 mg (Early Start)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/100 (58%)		32/55 (58.2%)		61/102 (59.8%)		63/100 (63%)		16/20 (80%)		22/37 (59.5%)		22/39 (56.4%)		25/52 (48.1%)		51/100 (51%)		56/94 (59.6%)
Blood and lymphatic system disorders
Anaemia	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		1/37 (2.7%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Coagulopathy	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Cardiac disorders
Ventricular extrasystoles	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Ear and labyrinth disorders
Paraesthesia ear	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Vertigo	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		1/100 (1%)		0/94 (0%)
Gastrointestinal disorders
Constipation	5/100 (5%)		3/55 (5.5%)		5/102 (4.9%)		6/100 (6%)		1/20 (5%)		2/37 (5.4%)		1/39 (2.6%)		1/52 (1.9%)		4/100 (4%)		7/94 (7.4%)
Diarrhoea	4/100 (4%)		5/55 (9.1%)		5/102 (4.9%)		6/100 (6%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		1/52 (1.9%)		2/100 (2%)		3/94 (3.2%)
Nausea	6/100 (6%)		1/55 (1.8%)		6/102 (5.9%)		6/100 (6%)		1/20 (5%)		2/37 (5.4%)		4/39 (10.3%)		2/52 (3.8%)		4/100 (4%)		7/94 (7.4%)
Dysphagia	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		1/39 (2.6%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Gastrooesophageal reflux disease	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		1/39 (2.6%)		0/52 (0%)		2/100 (2%)		0/94 (0%)
Haemorrhoids	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		1/37 (2.7%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Toothache	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		2/39 (5.1%)		1/52 (1.9%)		0/100 (0%)		3/94 (3.2%)
General disorders
Fatigue	5/100 (5%)		2/55 (3.6%)		3/102 (2.9%)		9/100 (9%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		1/52 (1.9%)		4/100 (4%)		5/94 (5.3%)
Asthenia	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Infections and infestations
COVID-19	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		2/37 (5.4%)		2/39 (5.1%)		0/52 (0%)		6/100 (6%)		3/94 (3.2%)
Influenza	3/100 (3%)		1/55 (1.8%)		7/102 (6.9%)		1/100 (1%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Nasopharyngitis	12/100 (12%)		10/55 (18.2%)		10/102 (9.8%)		13/100 (13%)		2/20 (10%)		0/37 (0%)		0/39 (0%)		2/52 (3.8%)		4/100 (4%)		5/94 (5.3%)
Upper respiratory tract infection	3/100 (3%)		2/55 (3.6%)		6/102 (5.9%)		7/100 (7%)		0/20 (0%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Urinary tract infection	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		2/20 (10%)		2/37 (5.4%)		1/39 (2.6%)		3/52 (5.8%)		2/100 (2%)		2/94 (2.1%)
Bronchitis	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		2/37 (5.4%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Tooth infection	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		1/52 (1.9%)		1/100 (1%)		1/94 (1.1%)
Injury, poisoning and procedural complications
Fall	5/100 (5%)		5/55 (9.1%)		6/102 (5.9%)		14/100 (14%)		2/20 (10%)		2/37 (5.4%)		3/39 (7.7%)		10/52 (19.2%)		16/100 (16%)		16/94 (17%)
Ligament rupture	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Procedural pain	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		2/20 (10%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		1/94 (1.1%)
Skin laceration	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		3/52 (5.8%)		1/100 (1%)		1/94 (1.1%)
Investigations
Blood cholesterol increased	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Blood glucose increased	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		1/100 (1%)		0/94 (0%)
Transaminases increased	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Weight decreased	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Metabolism and nutrition disorders
Calcium deficiency	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Decreased appetite	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/100 (7%)		5/55 (9.1%)		9/102 (8.8%)		11/100 (11%)		1/20 (5%)		4/37 (10.8%)		3/39 (7.7%)		3/52 (5.8%)		7/100 (7%)		2/94 (2.1%)
Back pain	8/100 (8%)		3/55 (5.5%)		8/102 (7.8%)		13/100 (13%)		0/20 (0%)		4/37 (10.8%)		6/39 (15.4%)		5/52 (9.6%)		5/100 (5%)		8/94 (8.5%)
Musculoskeletal stiffness	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		1/37 (2.7%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Pain in extremity	2/100 (2%)		4/55 (7.3%)		5/102 (4.9%)		1/100 (1%)		0/20 (0%)		1/37 (2.7%)		2/39 (5.1%)		2/52 (3.8%)		2/100 (2%)		2/94 (2.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of skin	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		1/52 (1.9%)		0/100 (0%)		1/94 (1.1%)
Nervous system disorders
Dizziness	3/100 (3%)		4/55 (7.3%)		9/102 (8.8%)		6/100 (6%)		0/20 (0%)		2/37 (5.4%)		2/39 (5.1%)		1/52 (1.9%)		4/100 (4%)		4/94 (4.3%)
Headache	18/100 (18%)		6/55 (10.9%)		19/102 (18.6%)		21/100 (21%)		3/20 (15%)		5/37 (13.5%)		5/39 (12.8%)		1/52 (1.9%)		7/100 (7%)		12/94 (12.8%)
Parkinson's disease	1/100 (1%)		4/55 (7.3%)		9/102 (8.8%)		8/100 (8%)		1/20 (5%)		1/37 (2.7%)		0/39 (0%)		1/52 (1.9%)		0/100 (0%)		0/94 (0%)
Paraesthesia	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		1/100 (1%)		2/94 (2.1%)
Restless legs syndrome	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Somnolence	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		1/39 (2.6%)		0/52 (0%)		1/100 (1%)		1/94 (1.1%)
Transient ischaemic attack	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Psychiatric disorders
Anxiety	4/100 (4%)		0/55 (0%)		9/102 (8.8%)		5/100 (5%)		1/20 (5%)		1/37 (2.7%)		2/39 (5.1%)		1/52 (1.9%)		1/100 (1%)		4/94 (4.3%)
Depression	1/100 (1%)		3/55 (5.5%)		3/102 (2.9%)		3/100 (3%)		1/20 (5%)		2/37 (5.4%)		0/39 (0%)		0/52 (0%)		2/100 (2%)		4/94 (4.3%)
Insomnia	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		4/37 (10.8%)		2/39 (5.1%)		3/52 (5.8%)		2/100 (2%)		2/94 (2.1%)
Reproductive system and breast disorders
Erectile dysfunction	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		0/37 (0%)		2/39 (5.1%)		0/52 (0%)		1/100 (1%)		1/94 (1.1%)
Respiratory, thoracic and mediastinal disorders
Cough	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		2/37 (5.4%)		1/39 (2.6%)		1/52 (1.9%)		1/100 (1%)		2/94 (2.1%)
Oropharyngeal pain	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		1/37 (2.7%)		1/39 (2.6%)		0/52 (0%)		2/100 (2%)		1/94 (1.1%)
Atelectasis	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Diaphragmatic paralysis	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Hypoxia	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Skin and subcutaneous tissue disorders
Rash	3/100 (3%)		1/55 (1.8%)		0/102 (0%)		5/100 (5%)		0/20 (0%)		0/37 (0%)		3/39 (7.7%)		0/52 (0%)		0/100 (0%)		2/94 (2.1%)
Skin irritation	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Skin ulcer	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		1/20 (5%)		0/37 (0%)		0/39 (0%)		0/52 (0%)		0/100 (0%)		0/94 (0%)
Vascular disorders
Hypertension	0/100 (0%)		0/55 (0%)		0/102 (0%)		0/100 (0%)		0/20 (0%)		2/37 (5.4%)		2/39 (5.1%)		0/52 (0%)		5/100 (5%)		2/94 (2.1%)

Limitations/Caveats

The study did not meet its primary outcome measure for year 1 and did not demonstrate efficacy on key secondary outcome measures; additional pre-specified analyses at week 72 confirmed the study did not provide evidence of efficacy; resulting in the development of BIIB054 for Parkinson's disease to be discontinued and SPARK study was closed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Our agreement is subject to confidentiality but generally the PI can publish, for non-commercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.

Results Point of Contact

Name/Title	US Biogen Clinical Trial Center
Organization	Biogen
Phone	866-633-4636
Email	clinicaltrials@biogen.com

Responsible Party:

Biogen

ClinicalTrials.gov Identifier:

NCT03318523

Other Study ID Numbers:

228PD201
2016-004610-95

First Posted:

Oct 24, 2017

Last Update Posted:

Feb 28, 2022

Last Verified:

Feb 1, 2022