Evaluating the Efficacy, Safety, Pharmacokinetics, and Ph... | NCT03318523 | Trialant
NCT03318523
Sponsor
Biogen
Status
Terminated
Last Update Posted
Feb 28, 2022Actual
Enrollment
357Actual
Phase
Phase 2
Conditions
Parkinson's Disease
Interventions
Placebo
BIIB054
Countries
United States
Austria
Canada
France
Germany
Israel
Italy
Spain
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03318523
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
228PD201
Secondary IDs
ID
Type
Description
Link
2016-004610-95
EudraCT Number
Brief Title
Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Participants With Parkinson's Disease
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
Acronym
SPARK
Organization
BiogenINDUSTRY
Status Module
Record Verification Date
Feb 2022
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
SPARK did not meet it's primary outcome measure for year 1 and failed to meet secondary outcome measures resulting in the development of BIIB054 (cinpanemab) for Parkinson's disease to be discontinued and SPARK study was closed.
Expanded Access Info
No
Start Date
Jan 10, 2018Actual
Primary Completion Date
Oct 26, 2020Actual
Completion Date
Apr 29, 2021Actual
First Submitted Date
Oct 19, 2017
First Submission Date that Met QC Criteria
Oct 19, 2017
First Posted Date
Oct 24, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Oct 25, 2021
Results First Submitted that Met QC Criteria
Oct 25, 2021
Results First Posted Date
Nov 23, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Feb 15, 2022
Last Update Posted Date
Feb 28, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
BiogenINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Detailed Description
Not provided
Conditions Module
Conditions
Parkinson's Disease
Keywords
BIIB054
Alpha-synuclein
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
357Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo
Placebo Comparator
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
BIIB054 250 mg
Experimental
Participants will receive BIIB054 250 milligrams (mg) intravenous (IV) infusion on Day 1 and then every 4 weeks.
Drug: BIIB054
BIIB054 1250 mg
Experimental
Participants will receive BIIB054 1250 mg IV infusion on Day 1 and then every 4 weeks.
Drug: BIIB054
BIIB054 3500 mg
Experimental
Participants will receive BIIB054 3500 mg IV infusion on Day 1 and then every 4 weeks.
Drug: BIIB054
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Placebo
Drug
Administered as specified in the treatment arm
Placebo
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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
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.
Baseline, Week 52
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
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.
Baseline, Week 72
Secondary Outcomes
Measure
Description
Time Frame
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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.
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
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
40 Years
Maximum Age
80 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Medical Director
Biogen
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
University of Alabama at Birmingham
Birmingham
Alabama
35233
United States
St. Joseph's Hopsital & Medical Center- Barrow Neurological Institute
Hutchison RM, Fraser K, Yang M, Fox T, Hirschhorn E, Njingti E, Scott D, Bedell BJ, Kistner KM, Cedarbaum JM, Evans KC, Graham D, Martarello L, Mollenhauer B, Lang AE, Dam T, Beaver J. Cinpanemab in Early Parkinson Disease: Evaluation of Biomarker Results From the Phase 2 SPARK Clinical Trial. Neurology. 2024 Mar 12;102(5):e209137. doi: 10.1212/WNL.0000000000209137. Epub 2024 Feb 5.
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.
Recruitment Details
Participants were enrolled at 75 investigational sites from 10 January 2018 to 29 April 2021.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
PC Period: Placebo
Participants received BIIB054-matching placebo, intravenous (IV) infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at 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.
Baseline, Week 96
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
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.
Baseline, Week 52
Change From Baseline in MDS-UPDRS Subpart I Score at 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.
Baseline, Weeks 72 and 96
Change From Baseline in MDS-UPDRS Subpart II Score at 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.
Baseline, Week 52
Change From Baseline in MDS-UPDRS Subpart II Score at 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.
Baseline, Weeks 72 and 96
Change From Baseline in MDS-UPDRS Subpart III Score at 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.
Baseline, Week 52
Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 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.
Baseline, Weeks 72 and 96
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
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.
Baseline, Week 52
Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at 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.
Baseline, Week 52
Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at 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.
Baseline, Week 52
Percentage of Participants With Anti-BIIB054 Antibodies in the Serum
Up to Week 144
Phoenix
Arizona
85013
United States
Research Site
La Jolla
California
92093-0886
United States
Cedars Sinai
Los Angeles
California
90048
United States
University of California San Francisco Medical Center
San Francisco
California
94158
United States
Research Site
Stanford
California
94305
United States
University of Colorado Health
Aurora
Colorado
80045
United States
Rocky Mountain Movement Disorders Center, PC
Englewood
Colorado
80113
United States
Parkinson's Disease and Movement Disorders Centerf
Boca Raton
Florida
33486
United States
Mayo Clinic Hospital
Jacksonville
Florida
32224
United States
Bioclinica Research
Orlando
Florida
32806
United States
USF Health Byrd Institute
Tampa
Florida
33616
United States
Northwestern University PD and Movement Disorders Center
Chicago
Illinois
60611
United States
Research Site
Chicago
Illinois
60612
United States
University of Kansas Medical Center Research Institute
Kansas City
Kansas
66160
United States
Ochsner Health System
New Orleans
Louisiana
70121
United States
Massachusetts General Hospital
Boston
Massachusetts
02114
United States
Boston University Medical Center
Boston
Massachusetts
02118
United States
Quest Research Institute
Farmington Hills
Michigan
48334
United States
NYU Langone Health Center
New York
New York
10017
United States
Research Site
New York
New York
10032
United States
Research Site
Durham
North Carolina
27705
United States
Wake Forest Baptist Health
Winston-Salem
North Carolina
27157
United States
The Cleveland Clinic Foundation
Cleveland
Ohio
44106
United States
Research Site
Philadelphia
Pennsylvania
19107
United States
University of Pittsburgh Medical Center Health System
Pittsburgh
Pennsylvania
15213
United States
Medical University of South Carolina
Charleston
South Carolina
29425
United States
Research Site
Nashville
Tennessee
37232
United States
Research Site
Houston
Texas
77030
United States
Booth Gardner Parkinson's Care Center at Evergreen Health
Kirkland
Washington
98034
United States
Inland Northwest Research
Spokane
Washington
99204
United States
Medical College of Wisconsin
Milwaukee
Wisconsin
53226
United States
Research Site
Innsbruck
6020
Austria
University Health Network
Toronto
Ontario
M5T 2S8
Canada
Montreal Neurological Institute Clinical Research Unit
Montreal
Quebec
H3A 2B4
Canada
Research Name
Toulouse
Haute Garonne
31059
France
CHU Nantes - Hopital Nord Laënnec
Nantes
Loire Atlantique
44093
France
Hopital Roger Salengro - CHU Lille
Lille
Nord
59037
France
Hôpital Henri Mondor
Créteil
Val De Marne
94010
France
Research Site
Paris
75013
France
Universitaetsklinikum Ulm
Ulm
Baden-Wurttemberg
89081
Germany
Klinikum rechts der Isar der TU Muenchen
Munich
Bavaria
81675
Germany
Universitaetsklinikum Wuerzburg
Würzburg
Bavaria
97080
Germany
Paracelsus-Elena-Klinik
Kassel
Hesse
34128
Germany
Universitaetsklinikum Aachen AOeR
Aachen
North Rhine-Westphalia
52074
Germany
Research Site
Bochum
North Rhine-Westphalia
44791
Germany
Research Site
Haifa
3109601
Israel
Research Site
Tel Aviv
6423906
Israel
I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo
Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
Salerno
84131
Italy
Azienda Ospedaliera Santa Maria di Terni
Terni
05100
Italy
Hospital General de Catalunya
Sant Cugat Del Vallés
Barcelona
08190
Spain
Research Site
Móstoles
Madrid
28938
Spain
Clinica Universidad de Navarra
Pamplona
Navarre
31008
Spain
Biocruces Health Research Institute
Barakaldo
Vizcaya
48903
Spain
Hospital Clinic De Barcalona
Barcelona
08036
Spain
Hospital Santa Creu i Sant Pau
Barcelona
08041
Spain
Research Site
Madrid
28006
Spain
Research Site
Madrid
28007
Spain
Research Site
Madrid
28034
Spain
Research Site
Seville
41013
Spain
Research Site
Cambridge
Cambridgeshire
CB2 0QQ
United Kingdom
Salford Royal
Salford
Greater Manchester
M6 8HD
United Kingdom
Research Site
Oxford
Oxfordshire
OX3 9DU
United Kingdom
Clinical Ageing Research Unit
Newcastle upon Tyne
Tyne & Wear
NE4 5PL
United Kingdom
Royal Hallamshire Hospital
Sheffield
West Midlands
S10 2JF
United Kingdom
Research Site
London
WC1N 3BG
United Kingdom
Derived
Lang AE, Siderowf AD, Macklin EA, Poewe W, Brooks DJ, Fernandez HH, Rascol O, Giladi N, Stocchi F, Tanner CM, Postuma RB, Simon DK, Tolosa E, Mollenhauer B, Cedarbaum JM, Fraser K, Xiao J, Evans KC, Graham DL, Sapir I, Inra J, Hutchison RM, Yang M, Fox T, Budd Haeberlein S, Dam T; SPARK Investigators. Trial of Cinpanemab in Early Parkinson's Disease. N Engl J Med. 2022 Aug 4;387(5):408-420. doi: 10.1056/NEJMoa2203395.
Hutchison RM, Evans KC, Fox T, Yang M, Barakos J, Bedell BJ, Cedarbaum JM, Brys M, Siderowf A, Lang AE. Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson's disease trial. BMC Neurol. 2021 Nov 23;21(1):459. doi: 10.1186/s12883-021-02470-8.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
FG002
PC Period: BIIB054 1250 mg (Early Start)
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
FG003
PC Period: BIIB054 3500 mg (Early Start)
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
FG004
DBE Period: Placebo to BIIB054 250 mg (Delayed Start)
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.
FG005
DBE Period: Placebo to BIIB054 1250 mg (Delayed Start)
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.
FG006
DBE Period: Placebo to BIIB054 3500 mg (Delayed Start)
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.
FG007
DBE Period: BIIB054 250 mg (Early Start)
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.
FG008
DBE Period: BIIB054 1250 mg (Early Start)
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.
FG009
DBE Period: BIIB054 3500 mg (Early Start)
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.
FG000100 subjects
FG00155 subjects
FG002102 subjects
FG003100 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
COMPLETED
FG00096 subjects
FG00153 subjects
FG002100 subjects
FG00396 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
NOT COMPLETED
FG0004 subjects
FG0012 subjects
FG0022 subjects
FG0034 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
Consent Withdrawn
FG0003 subjects
FG0012 subjects
FG0020 subjects
FG0034 subjects
FG004
DBE Period:Year 2 to EOS (Up to 3 Years)
Type
Comment
Milestone Data
STARTED
Out of 345 participants who completed the PC Period, only 344 entered the DBE Period.
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG00420 subjects
FG00537 subjects
FG00639 subjects
FG00752 subjects
FG008100 subjects
FG00996 subjects
Number of Participants Dosed
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Intent-to-treat (ITT) population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
PC Period: Placebo
Participants received BIIB054-matching placebo, intravenous (IV) infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
BG001
PC Period: BIIB054 250 mg (Early Start)
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
BG002
PC Period: BIIB054 1250 mg (Early Start)
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
BG003
PC Period: BIIB054 3500 mg (Early Start)
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000100
BG00155
BG002102
BG003100
BG004357
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
ParticipantsBG000100
ParticipantsBG00155
ParticipantsBG002102
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000100
ParticipantsBG00155
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000100
ParticipantsBG00155
ParticipantsBG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000100
ParticipantsBG00155
ParticipantsBG002
Baseline Movement Disorder Society Sponsored Revision of the Unified PD Rating Scale Total Score
Movement Disorder Society Sponsored Revision of the Unified PD Rating Scale (MDS-UPDRS) is multimodal scale assessing impairment and disability consisting of 4 parts. Part I: non-motor experiences of daily living and has 2 components (13 questions[Q], Range[R] 0-52). Part II: motor experiences of daily living (13 Q, R 0-52). Part III: motor signs of PD and was administered by rater (33 Q, R 0-132). Numeric score for each question is between 0-4; 0=Normal,1=Slight,2=Mild,3=Moderate,4=Severe. MDS-UPDRS Total Score=sum of Parts I, II, and III (R 0-236). Higher score=more severe symptoms of PD.
Mean
Standard Deviation
score on a scale
Title
Denominators
Categories
ParticipantsBG000100
ParticipantsBG001
Baseline MDS-UPDRS Subpart I Score
MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. It is separated into 4 subscales: Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the 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.
Mean
Standard Deviation
score on a scale
Title
Denominators
Categories
ParticipantsBG000100
ParticipantsBG001
Baseline MDS-UPDRS Subpart II Score
MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the 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.
Mean
Standard Deviation
score on a scale
Title
Denominators
Categories
ParticipantsBG000100
ParticipantsBG00155
Participants
Baseline MDS-UPDRS Subpart III Score
MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part III assessed the motor signs of Parkinson's Disease (PD) and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD.
Mean
Standard Deviation
score on a scale
Title
Denominators
Categories
ParticipantsBG000100
ParticipantsBG00155
Baseline Total Striatum Striatal Binding Ratio (SBR)
ITT population. Number analyzed is the number of participants analyzed for this study specific baseline measure.
Mean
Standard Deviation
striatal binding ratio
Title
Denominators
Categories
ParticipantsBG000100
ParticipantsBG00155
ParticipantsBG002
Baseline Total Putamen SBR
ITT population. Number analyzed is the number of participants analyzed for this study specific baseline measure.
Mean
Standard Deviation
striatal binding ratio
Title
Denominators
Categories
ParticipantsBG000100
ParticipantsBG00155
ParticipantsBG002
Baseline Total Caudate SBR
ITT population. Number analyzed is the number of participants analyzed for this study specific baseline measure.
Mean
Standard Deviation
striatal binding ratio
Title
Denominators
Categories
ParticipantsBG000100
ParticipantsBG00155
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52
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.
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.
Posted
Mean
Standard Error
score on a scale
Baseline, Week 52
ID
Title
Description
OG000
PC Period: Placebo
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG001
PC Period: BIIB054 250 mg (Early Start)
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG002
PC Period: BIIB054 1250 mg (Early Start)
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
OG003
PC Period: BIIB054 3500 mg (Early Start)
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG00053
OG00129
OG00257
OG003
Title
Denominators
Categories
Title
Measurements
OG00010.78± 1.490
OG00110.48± 1.951
OG00211.29± 1.446
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Change From Baseline in MDS-UPDRS Total Score at Week 52
Mixed Model for Repeated Measures
0.8976
Difference
-0.30
2-Sided
95
-4.888
4.287
Superiority
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.
Primary
Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 72
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.
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.
Posted
Mean
Standard Error
score on a scale
Baseline, Week 72
ID
Title
Description
OG000
PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)
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.
Secondary
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
The safety population was defined as all participants who received at least one dose of study treatment (BIIB054).
Posted
Number
percentage of participants
Up to 3 years
ID
Title
Description
OG000
PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)
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.
OG001
PC Period: Early Start BIIB054 250 mg
Secondary
Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at 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.
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.
Posted
Mean
Standard Error
score on a scale
Baseline, Week 96
ID
Title
Description
OG000
PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)
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.
Secondary
Serum Concentration of BIIB054
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.
Posted
Mean
Standard Deviation
micrograms per milliliter (ug/mL)
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
ID
Title
Description
OG000
BIIB054 250 mg
Participants received BIIB054, 250 mg, IV infusion, from Day 1 up to EOS (approximately 3 years).
OG001
BIIB054 1250 mg
Participants received BIIB054, 1250 mg, IV infusion, from Day 1 up to EOS (approximately 3 years).
OG002
BIIB054 3500 mg
Participants received BIIB054, 3500 mg, IV infusion, from Day 1 up to EOS (approximately 3 years).
Units
Counts
Participants
Secondary
Change From Baseline in MDS-UPDRS Subpart I Score at 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.
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.
Posted
Mean
Standard Error
score on a scale
Baseline, Week 52
ID
Title
Description
OG000
PC Period: Placebo
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG001
PC Period: BIIB054 250 mg (Early Start)
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG002
PC Period: BIIB054 1250 mg (Early Start)
Secondary
Change From Baseline in MDS-UPDRS Subpart I Score at 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.
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.
Posted
Mean
Standard Error
score on a scale
Baseline, Weeks 72 and 96
ID
Title
Description
OG000
PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)
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.
OG001
PC Period: Early Start BIIB054 250 mg
Secondary
Change From Baseline in MDS-UPDRS Subpart II Score at 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.
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.
Posted
Mean
Standard Error
score on a scale
Baseline, Week 52
ID
Title
Description
OG000
PC Period: Placebo
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG001
PC Period: BIIB054 250 mg (Early Start)
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG002
PC Period: BIIB054 1250 mg (Early Start)
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Secondary
Change From Baseline in MDS-UPDRS Subpart II Score at 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.
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.
Posted
Mean
Standard Error
score on a scale
Baseline, Weeks 72 and 96
ID
Title
Description
OG000
PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)
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.
OG001
PC Period: Early Start BIIB054 250 mg
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Secondary
Change From Baseline in MDS-UPDRS Subpart III Score at 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.
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.
Posted
Mean
Standard Error
score on a scale
Baseline, Week 52
ID
Title
Description
OG000
PC Period: Placebo
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG001
PC Period: BIIB054 250 mg (Early Start)
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG002
PC Period: BIIB054 1250 mg (Early Start)
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Secondary
Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 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.
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.
Posted
Mean
Standard Error
score on a scale
Baseline, Weeks 72 and 96
ID
Title
Description
OG000
PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)
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.
OG001
PC Period: Early Start BIIB054 250 mg
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Secondary
Change From Baseline in Striatal Binding Ratio (SBR) in the Putamen as Measured by Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter (DaT) at Week 52
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.
The pharmacodynamic population was defined as a subset of the ITT population with at least 1 post-baseline pharmacodynamic measurement.
Posted
Mean
Standard Error
striatal binding ratio
Baseline, Week 52
ID
Title
Description
OG000
PC Period: Placebo
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG001
PC Period: BIIB054 250 mg (Early Start)
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG002
PC Period: BIIB054 1250 mg (Early Start)
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
OG003
Secondary
Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at 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.
The pharmacodynamic population was defined as a subset of the ITT population with at least 1 post-baseline pharmacodynamic measurement.
Posted
Mean
Standard Error
striatal binding ratio
Baseline, Week 52
ID
Title
Description
OG000
PC Period: Placebo
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG001
PC Period: BIIB054 250 mg (Early Start)
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG002
PC Period: BIIB054 1250 mg (Early Start)
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
OG003
PC Period: BIIB054 3500 mg (Early Start)
Secondary
Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at 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.
The pharmacodynamic population was defined as a subset of the ITT population with at least 1 post-baseline pharmacodynamic measurement.
Posted
Mean
Standard Error
striatal binding ratio
Baseline, Week 52
ID
Title
Description
OG000
PC Period: Placebo
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG001
PC Period: BIIB054 250 mg (Early Start)
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG002
PC Period: BIIB054 1250 mg (Early Start)
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
OG003
PC Period: BIIB054 3500 mg (Early Start)
Secondary
Percentage of Participants With Anti-BIIB054 Antibodies in the Serum
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.
Posted
Number
percentage of participants
Up to Week 144
ID
Title
Description
OG000
PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled)
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.
OG001
PC Period: Early Start BIIB054 250 mg
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG002
PC Period: Early Start BIIB054 1250 mg
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
OG003
PC Period: Early Start BIIB054 3500 mg
Time Frame
Up to 3 years
Description
Safety Population included all participants who received at least one dose of the study treatment (BIIB054 250 mg, 1250 mg, 3500 mg).
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
PC Period: Placebo
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
0
100
7
100
58
100
EG001
PC Period: BIIB054 250 mg (Early Start)
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
0
55
4
55
32
55
EG002
PC Period: BIIB054 1250 mg (Early Start)
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
0
102
4
102
61
102
EG003
PC Period: BIIB054 3500 mg (Early Start)
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
0
100
6
100
63
100
EG004
DBE Period: Placebo to BIIB054 250 mg (Delayed Start)
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.
0
20
2
20
16
20
EG005
DBE Period: Placebo to BIIB054 1250 mg (Delayed Start)
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.
0
37
3
37
22
37
EG006
DBE Period: Placebo to BIIB054 3500 mg (Delayed Start)
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.
0
39
3
39
22
39
EG007
DBE Period: BIIB054 250 mg (Early Start)
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.
0
52
3
52
25
52
EG008
DBE Period: BIIB054 1250 mg (Early Start)
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.
0
100
5
100
51
100
EG009
DBE Period: BIIB054 3500 mg (Early Start)
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.
1
94
7
94
56
94
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Monoclonal B-cell lymphocytosis
Blood and lymphatic system disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG0030 affected100 at risk
EG004
Bradycardia
Cardiac disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Palpitations
Cardiac disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Pericarditis
Cardiac disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0021 affected102 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0011 affected55 at risk
EG0020 affected102 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0001 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Impaired healing
General disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Hepatitis toxic
Hepatobiliary disorders
MedDRA Version 23.1
Systematic Assessment
EG0001 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Anaphylactic reaction
Immune system disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
COVID-19
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG0001 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Perirectal abscess
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Viral infection
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Arthropod sting
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Jaw fracture
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Muscle strain
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0001 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Pelvic fracture
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Post lumbar puncture syndrome
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0001 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Road traffic accident
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Spinal compression fracture
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Ulna fracture
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Arthritis
Musculoskeletal and connective tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Lumbar spinal stenosis
Musculoskeletal and connective tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0011 affected55 at risk
EG0020 affected102 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Rotator cuff syndrome
Musculoskeletal and connective tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0021 affected102 at risk
EG003
Spinal stenosis
Musculoskeletal and connective tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0011 affected55 at risk
EG0020 affected102 at risk
EG003
Spondylolisthesis
Musculoskeletal and connective tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Basal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Glioblastoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Invasive lobular breast carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Prostate cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0011 affected55 at risk
EG0020 affected102 at risk
EG003
Intracranial mass
Nervous system disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Sciatica
Nervous system disorders
MedDRA Version 23.1
Systematic Assessment
EG0001 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Depression
Psychiatric disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0021 affected102 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0021 affected102 at risk
EG003
Benign prostatic hyperplasia
Reproductive system and breast disorders
MedDRA Version 23.1
Systematic Assessment
EG0001 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Acute respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0001 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Constipation
Gastrointestinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0005 affected100 at risk
EG0013 affected55 at risk
EG0025 affected102 at risk
EG0036 affected100 at risk
EG0041 affected20 at risk
EG0052 affected37 at risk
EG0061 affected39 at risk
EG0071 affected52 at risk
EG0084 affected100 at risk
EG0097 affected94 at risk
Diarrhoea
Gastrointestinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0004 affected100 at risk
EG0015 affected55 at risk
EG0025 affected102 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0006 affected100 at risk
EG0011 affected55 at risk
EG0026 affected102 at risk
EG003
Fatigue
General disorders
MedDRA Version 23.1
Systematic Assessment
EG0005 affected100 at risk
EG0012 affected55 at risk
EG0023 affected102 at risk
EG003
COVID-19
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Influenza
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG0003 affected100 at risk
EG0011 affected55 at risk
EG0027 affected102 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG00012 affected100 at risk
EG00110 affected55 at risk
EG00210 affected102 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG0003 affected100 at risk
EG0012 affected55 at risk
EG0026 affected102 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0005 affected100 at risk
EG0015 affected55 at risk
EG0026 affected102 at risk
EG003
Ligament rupture
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0007 affected100 at risk
EG0015 affected55 at risk
EG0029 affected102 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0008 affected100 at risk
EG0013 affected55 at risk
EG0028 affected102 at risk
EG003
Musculoskeletal stiffness
Musculoskeletal and connective tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0002 affected100 at risk
EG0014 affected55 at risk
EG0025 affected102 at risk
EG003
Dizziness
Nervous system disorders
MedDRA Version 23.1
Systematic Assessment
EG0003 affected100 at risk
EG0014 affected55 at risk
EG0029 affected102 at risk
EG003
Headache
Nervous system disorders
MedDRA Version 23.1
Systematic Assessment
EG00018 affected100 at risk
EG0016 affected55 at risk
EG00219 affected102 at risk
EG003
Parkinson's disease
Nervous system disorders
MedDRA Version 23.1
Systematic Assessment
EG0001 affected100 at risk
EG0014 affected55 at risk
EG0029 affected102 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA Version 23.1
Systematic Assessment
EG0004 affected100 at risk
EG0010 affected55 at risk
EG0029 affected102 at risk
EG003
Depression
Psychiatric disorders
MedDRA Version 23.1
Systematic Assessment
EG0001 affected100 at risk
EG0013 affected55 at risk
EG0023 affected102 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0003 affected100 at risk
EG0011 affected55 at risk
EG0020 affected102 at risk
EG003
Hypertension
Vascular disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Asthenia
General disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Bronchitis
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Tooth infection
Infections and infestations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Skin laceration
Injury, poisoning and procedural complications
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Restless legs syndrome
Nervous system disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Somnolence
Nervous system disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Skin irritation
Skin and subcutaneous tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Skin ulcer
Skin and subcutaneous tissue disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Coagulopathy
Blood and lymphatic system disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Ventricular extrasystoles
Cardiac disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Paraesthesia ear
Ear and labyrinth disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Blood cholesterol increased
Investigations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Blood glucose increased
Investigations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Transaminases increased
Investigations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Weight decreased
Investigations
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Calcium deficiency
Metabolism and nutrition disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Benign neoplasm of skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Erectile dysfunction
Reproductive system and breast disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Atelectasis
Respiratory, thoracic and mediastinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Diaphragmatic paralysis
Respiratory, thoracic and mediastinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA Version 23.1
Systematic Assessment
EG0000 affected100 at risk
EG0010 affected55 at risk
EG0020 affected102 at risk
EG003
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.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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.
Change From Baseline in MDS-UPDRS Total Score at Week 52
Mixed Model for Repeated Measures
0.7960
Difference
0.50
2-Sided
95
-3.310
4.312
Superiority
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.
OG000
OG003
Change From Baseline in MDS-UPDRS Total Score at Week 52
Mixed Model for Repeated Measures
0.9695
Difference
0.08
2-Sided
95
-3.805
3.956
Superiority
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.
OG001
PC Period: Early Start BIIB054 250 mg
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG002
PC Period: Early Start BIIB054 1250 mg
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
OG003
PC Period: Early Start BIIB054 3500 mg
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG00068
OG00132
OG00262
OG00364
Title
Denominators
Categories
Title
Measurements
OG0007.11± 1.476
OG0016.83± 2.032
OG0028.66± 1.496
OG0036.94± 1.508
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Change From Baseline in MDS-UPDRS Total Score at Week 72
Mixed Model for Repeated Measures
0.9093
Difference
-0.28
2-Sided
95
-5.035
4.483
Superiority
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.
OG000
OG002
Change From Baseline in MDS-UPDRS Total Score at Week 72
Mixed Model for Repeated Measures
0.4327
Difference
1.55
2-Sided
95
-2.336
5.440
Superiority
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.
OG000
OG003
Change From Baseline in MDS-UPDRS Total Score at Week 72
Mixed Model with repeated Measures
0.9330
Difference
-0.17
2-Sided
95
-4.051
3.719
Superiority
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.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG002
PC Period: Early Start BIIB054 1250 mg
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
OG003
PC Period: Early Start BIIB054 3500 mg
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG00096
OG00155
OG002102
OG003100
Title
Denominators
Categories
AEs
Title
Measurements
OG00077.1
OG00185.5
OG00289.2
OG00393.0
SAEs
Title
Measurements
OG0008.3
OG00110.9
OG0028.8
OG003
OG001
PC Period: Early Start BIIB054 250 mg
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG002
PC Period: Early Start BIIB054 1250 mg
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
OG003
PC Period: Early Start BIIB054 3500 mg
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG00067
OG00128
OG00262
OG00359
Title
Denominators
Categories
Title
Measurements
OG0007.88± 1.616
OG0018.28± 2.317
OG0028.71± 1.628
OG0038.87± 1.659
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Model for Repeated Measures
0.8828
Difference
0.41
2-Sided
95
-5.013
5.825
Superiority
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.
OG000
OG002
Mixed Model for Repeated Measure
0.7019
Difference
0.84
2-Sided
95
-3.458
5.128
Superiority
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.
OG000
OG003
Mixed Model for Repeated Measures
0.6519
Difference
0.99
2-Sided
95
-3.323
5.301
Superiority
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.
OG00075
OG001139
OG002139
Title
Denominators
Categories
Baseline (Pre-dose)
ParticipantsOG00048
ParticipantsOG00195
ParticipantsOG00292
Title
Measurements
OG0000.00± 0.000
OG0017.47± 51.281
OG0020.01± 0.065
Baseline (1 Hour Post-dose)
ParticipantsOG00062
ParticipantsOG001121
ParticipantsOG002114
Title
Measurements
OG000
Week 4 (Pre-dose)
ParticipantsOG00046
ParticipantsOG00195
ParticipantsOG00291
Title
Measurements
OG000
Week 4 (1 Hour Post-dose)
ParticipantsOG00047
ParticipantsOG00194
ParticipantsOG00291
Title
Measurements
OG000
Week 8 (Pre-dose)
ParticipantsOG00063
ParticipantsOG001125
ParticipantsOG002122
Title
Measurements
OG000
Week 8 (1 Hour Post-dose)
ParticipantsOG00064
ParticipantsOG001127
ParticipantsOG002122
Title
Measurements
OG000
Week 12 (Pre-dose)
ParticipantsOG00050
ParticipantsOG00197
ParticipantsOG00296
Title
Measurements
OG000
Week 12 (1 Hour Post-dose)
ParticipantsOG00054
ParticipantsOG00199
ParticipantsOG00297
Title
Measurements
OG000
Week 16 (Pre-dose)
ParticipantsOG00051
ParticipantsOG00199
ParticipantsOG00298
Title
Measurements
OG000
Week 16 (1 Hour Post-dose)
ParticipantsOG00050
ParticipantsOG00199
ParticipantsOG00298
Title
Measurements
OG000
Week 24 (Pre-dose)
ParticipantsOG00054
ParticipantsOG00198
ParticipantsOG00294
Title
Measurements
OG000
Week 24 (1 Hour Post-dose)
ParticipantsOG00046
ParticipantsOG00190
ParticipantsOG00287
Title
Measurements
OG000
Week 32 (Pre-dose)
ParticipantsOG00011
ParticipantsOG00119
ParticipantsOG00224
Title
Measurements
OG000
Week 32 (1 Hour Post-dose)
ParticipantsOG00015
ParticipantsOG00125
ParticipantsOG00228
Title
Measurements
OG000
Week 36 (Pre-dose)
ParticipantsOG00051
ParticipantsOG001100
ParticipantsOG00296
Title
Measurements
OG000
Week 36 (1 Hour Post-dose)
ParticipantsOG00051
ParticipantsOG001100
ParticipantsOG00295
Title
Measurements
OG000
Week 44 (Pre-dose)
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0027
Title
Measurements
OG000
Week 44 (1 Hour Post-dose)
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0028
Title
Measurements
OG000
Week 52 (Pre-dose)
ParticipantsOG00049
ParticipantsOG00198
ParticipantsOG00282
Title
Measurements
OG000
Week 52 (1 Hour Post-dose)
ParticipantsOG00035
ParticipantsOG00174
ParticipantsOG00264
Title
Measurements
OG000
Week 60 (Pre-dose)
ParticipantsOG00042
ParticipantsOG00186
ParticipantsOG00284
Title
Measurements
OG000
Week 60 (1 Hour Post-dose)
ParticipantsOG00041
ParticipantsOG00183
ParticipantsOG00280
Title
Measurements
OG000
Week 68 (Pre-dose)
ParticipantsOG0002
ParticipantsOG0013
ParticipantsOG0022
Title
Measurements
OG000
Week 68 (1 Hour Post-dose)
ParticipantsOG0002
ParticipantsOG0013
ParticipantsOG0022
Title
Measurements
OG000
Week 84 (Pre-dose)
ParticipantsOG00028
ParticipantsOG00150
ParticipantsOG00242
Title
Measurements
OG000
Week 84 (1 Hour Post-dose)
ParticipantsOG00038
ParticipantsOG00160
ParticipantsOG00252
Title
Measurements
OG000
Week 96 (Pre-dose)
ParticipantsOG00011
ParticipantsOG00118
ParticipantsOG00216
Title
Measurements
OG000
Week 96 (1 Hour Post-dose)
ParticipantsOG00010
ParticipantsOG00120
ParticipantsOG00216
Title
Measurements
OG000
Week 120 (Pre-dose)
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0027
Title
Measurements
OG000
Week 120 (1 Hour Post-dose)
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0027
Title
Measurements
OG000
Week 144 (Pre-dose)
ParticipantsOG0000
ParticipantsOG0011
ParticipantsOG0020
Title
Measurements
OG001
Week 144 (1 Hour Post-dose)
ParticipantsOG0000
ParticipantsOG0011
ParticipantsOG0020
Title
Measurements
OG001
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
OG003
PC Period: BIIB054 3500 mg (Early Start)
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG00053
OG00129
OG00257
OG00351
Title
Denominators
Categories
Title
Measurements
OG0001.43± 0.436
OG0010.90± 0.570
OG0021.56± 0.423
OG0031.65± 0.446
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Change from Baseline in MDS-UPDRS Subpart I Score at Week 52
Mixed Model for Repeated Measures
0.4327
Difference
-0.53
2-Sided
95
-1.851
0.794
Superiority
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.
OG000
OG002
Change from Baseline in MDS-UPDRS Subpart I Score at Week 52
Mixed Model for Repeated Measures
0.8155
Difference
0.13
2-Sided
95
-0.965
1.225
Superiority
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.
OG000
OG003
Change from Baseline in MDS-UPDRS Subpart I Score at Week 52
Mixed Model for Repeated Measures
0.7015
Difference
0.22
2-Sided
95
-0.899
1.334
Superiority
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.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
OG002
PC Period: Early Start BIIB054 1250 mg
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
OG003
PC Period: Early Start BIIB054 3500 mg
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG000100
OG00155
OG002102
OG003100
Title
Denominators
Categories
Change from Baseline at Week 72
ParticipantsOG00068
ParticipantsOG00132
ParticipantsOG00262
ParticipantsOG00364
Title
Measurements
OG0001.65± 0.395
OG0010.61± 0.538
OG0021.73± 0.402
OG003
Change from Baseline at Week 96
ParticipantsOG00067
ParticipantsOG00128
ParticipantsOG00262
ParticipantsOG00359
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Change from Baseline in MDS-UPDRS Subpart I Score at Week 72
Mixed Model for Repeated Measures
0.1038
Difference
-1.03
2-Sided
95
-2.276
0.213
Superiority
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.
OG000
OG002
Change from Baseline in MDS-UPDRS Subpart I Score at Week 72
Mixed Model for Repeated Measures
0.8689
Difference
0.09
2-Sided
95
-0.933
1.103
Superiority
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.
OG000
OG003
Change from Baseline in MDS-UPDRS Subpart I Score at Week 72
Mixed Model for Repeated Measures
0.9820
Difference
-0.01
2-Sided
95
-1.026
1.003
Superiority
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.
OG000
OG001
Change from Baseline in MDS-UPDRS Subpart I Score at Week 96
Mixed Model for Repeated Measures
0.6930
Difference
-0.26
2-Sided
95
-1.563
1.040
Superiority
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.
OG000
OG002
Change from Baseline in MDS-UPDRS Subpart I Score at Week 96
Mixed Model for Repeated Measures
0.9606
Difference
-0.03
2-Sided
95
-1.053
1.001
Superiority
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.
OG000
OG003
Change from Baseline in MDS-UPDRS Subpart I Score at Week 96
Mixed Model for Repeated Measures
0.6512
Difference
-0.24
2-Sided
95
-1.269
0.794
Superiority
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.
OG003
PC Period: BIIB054 3500 mg (Early Start)
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG00054
OG00129
OG00258
OG00351
Title
Denominators
Categories
Title
Measurements
OG0003.17± 0.473
OG0012.72± 0.621
OG0023.16± 0.460
OG0033.01± 0.486
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Change from Baseline in MDS-UPDRS Subpart II Score at Week 52
Mixed Model for Repeated Measures
0.5497
Difference
-0.44
2-Sided
95
-1.889
1.007
Superiority
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.
OG000
OG002
Change from Baseline in MDS-UPDRS Subpart II Score at Week 52
Mixed Model for Repeated Measures
0.9980
Difference
-0.00
2-Sided
95
-1.200
1.197
Superiority
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.
OG000
OG003
Change from Baseline in MDS-UPDRS Subpart II Score at Week 52
Mixed Model for Repeated Measures
0.8069
Difference
-0.15
2-Sided
95
-1.374
1.070
Superiority
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.
OG002
PC Period: Early Start BIIB054 1250 mg
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
OG003
PC Period: Early Start BIIB054 3500 mg
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG000100
OG00155
OG002102
OG003100
Title
Denominators
Categories
Change from Baseline at Week 72
ParticipantsOG00069
ParticipantsOG00133
ParticipantsOG00262
ParticipantsOG00364
Title
Measurements
OG0001.83± 0.491
OG0011.62± 0.672
OG0022.36± 0.497
OG003
Change from Baseline at Week 96
ParticipantsOG00067
ParticipantsOG00128
ParticipantsOG00262
ParticipantsOG00360
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Change from Baseline in MDS-UPDRS Subpart II Score at Week 72
Mixed Model for Repeated Measures
0.7968
Difference
-0.21
2-Sided
95
-1.786
1.372
Superiority
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.
OG000
OG002
Change from Baseline in MDS-UPDRS Subpart II Score at Week 72
Mixed Model for Repeated Measures
0.4211
Difference
0.53
2-Sided
95
-0.766
1.827
Superiority
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.
OG000
OG003
Change from Baseline in MDS-UPDRS Subpart II Score at Week 72
Mixed Model for Repeated Measures
0.8166
Difference
-0.15
2-Sided
95
-1.448
1.143
Superiority
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.
OG000
OG001
Change from Baseline in MDS-UPDRS Subpart II Score at Week 96
Mixed Model for Repeated Measures
0.5535
Difference
-0.53
2-Sided
95
-2.310
1.240
Superiority
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.
OG000
OG002
Change from Baseline in MDS-UPDRS Subpart II Score at Week 96
Mixed Model for Repeated Measures
0.4654
Difference
0.52
2-Sided
95
-0.881
1.922
Superiority
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.
OG000
OG003
Change from Baseline in MDS-UPDRS Subpart II Score at Week 96
Mixed Model for Repeated Measures
0.6184
Difference
0.36
2-Sided
95
-1.051
1.763
Superiority
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.
OG003
PC Period: BIIB054 3500 mg (Early Start)
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG00053
OG00129
OG00258
OG00351
Title
Denominators
Categories
Title
Measurements
OG0006.10± 1.083
OG0016.69± 1.419
OG0026.76± 1.046
OG0036.20± 1.104
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Change from Baseline in MDS-UPDRS Subpart III Score at Week 52
Mixed Model for Repeated Measures
0.7274
Difference
0.59
2-Sided
95
-2.742
3.925
Superiority
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.
OG000
OG002
Change from Baseline in MDS-UPDRS Subpart III Score at Week 52
Mixed Model for Repeated Measures
0.6385
Difference
0.66
2-Sided
95
-2.094
3.411
Superiority
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.
OG000
OG003
Change from Baseline in MDS-UPDRS Subpart III Score at Week 52
Mixed Model for Repeated Measures
0.9467
Difference
0.10
2-Sided
95
-2.718
2.910
Superiority
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.
OG002
PC Period: Early Start BIIB054 1250 mg
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
OG003
PC Period: Early Start BIIB054 3500 mg
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG000100
OG00155
OG002102
OG003100
Title
Denominators
Categories
Change from Baseline at Week 72
ParticipantsOG00068
ParticipantsOG00132
ParticipantsOG00262
ParticipantsOG00364
Title
Measurements
OG0003.64± 1.027
OG0014.48± 1.404
OG0024.49± 1.038
OG003
Change from Baseline at Week 96
ParticipantsOG00067
ParticipantsOG00128
ParticipantsOG00262
ParticipantsOG00360
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Change from Baseline in MDS-UPDRS Subpart III Score at Week 72
Mixed Model for Repeated Measures
0.6112
Difference
0.85
2-Sided
95
-2.423
4.114
Superiority
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.
OG000
OG002
Change from Baseline in MDS-UPDRS Subpart III Score at Week 72
Mixed Model for Repeated Measures
0.5270
Difference
0.86
2-Sided
95
-1.806
3.520
Superiority
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.
OG000
OG003
Change from Baseline in MDS-UPDRS Subpart III Score at Week 72
Mixed Model for Repeated Measures
0.9673
Difference
0.06
2-Sided
95
-2.608
2.719
Superiority
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.
OG000
OG001
Change from Baseline in MDS-UPDRS Subpart III Score at Week 96
Mixed Model for Repeated Measures
0.7455
Difference
0.65
2-Sided
95
-3.274
4.569
Superiority
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.
OG000
OG002
Change from Baseline in MDS-UPDRS Subpart III Score at Week 96
Mixed Model for Repeated Measures
0.9506
Difference
-0.10
2-Sided
95
-3.192
2.997
Superiority
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.
OG000
OG003
Change from Baseline in MDS-UPDRS Subpart III Score at Week 96
Mixed Model for Repeated Measures
0.6643
Difference
0.69
2-Sided
95
-2.422
3.794
Superiority
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.
PC Period: BIIB054 3500 mg (Early Start)
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG00091
OG00152
OG00297
OG00384
Title
Denominators
Categories
Title
Measurements
OG000-0.093± 0.0151
OG001-0.098± 0.0199
OG002-0.102± 0.0146
OG003-0.125± 0.0155
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Model for Repeated Measures
0.8274
Difference
-0.005
2-Sided
95
-0.0548
0.0438
Superiority
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.
OG000
OG002
Mixed Model for Repeated Measures
0.6671
Difference
-0.009
2-Sided
95
-0.0504
0.0323
Superiority
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.
OG000
OG003
Mixed Model for Repeated Measures
0.1313
Difference
-0.033
2-Sided
95
-0.0751
0.0098
Superiority
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.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG00091
OG00152
OG00297
OG00384
Title
Denominators
Categories
Title
Measurements
OG000-0.081± 0.0145
OG001-0.090± 0.0191
OG002-0.081± 0.0140
OG003-0.108± 0.0148
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Model for Repeated Measures
0.7079
Difference
-0.009
2-Sided
95
-0.0562
0.0382
Superiority
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.
OG000
OG002
Mixed Model for Repeated Measures
0.9835
Difference
-0.000
2-Sided
95
-0.0400
0.0392
Superiority
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.
OG000
OG003
Mixed Model for Repeated Measures
0.1869
Difference
-0.027
2-Sided
95
-0.0682
0.0134
Superiority
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.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Units
Counts
Participants
OG00091
OG00152
OG00297
OG00384
Title
Denominators
Categories
Title
Measurements
OG000-0.067± 0.0166
OG001-0.075± 0.0219
OG002-0.060± 0.0161
OG003-0.089± 0.0171
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Model for Repeated Measures
0.7585
Difference
-0.008
2-Sided
95
-0.0625
0.0456
Superiority
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.
OG000
OG002
Mixed Model for Repeated Measures
0.7808
Difference
0.006
2-Sided
95
-0.0391
0.0520
Superiority
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.
OG000
OG003
Mixed Model for Repeated Measures
0.3532
Difference
-0.022
2-Sided
95
-0.0691
0.0248
Superiority
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.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.