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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03318523
Recruitment Status : Terminated (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.)
First Posted : October 24, 2017
Results First Posted : November 23, 2021
Last Update Posted : February 28, 2022
Sponsor:
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Parkinson's Disease
Interventions Drug: Placebo
Drug: BIIB054
Enrollment 357
Recruitment Details Participants were enrolled at 75 investigational sites from 10 January 2018 to 29 April 2021.
Pre-assignment Details Participants with Parkinson's Disease (PD) were enrolled and randomized to receive placebo or BIIB054 250/1250/3500 milligrams (mg) for Year 1 in Placebo-Controlled (PC) Period. Following Year 1, participants on placebo (delayed start) were re-randomized to receive BIIB054 250/1250/3500 mg dose, and others on BIIB054 in Year 1 continued to receive the same dose until their Week 96 visit.
Arm/Group Title PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start) DBE Period: Placebo to BIIB054 250 mg (Delayed Start) DBE Period: Placebo to BIIB054 1250 mg (Delayed Start) DBE Period: Placebo to BIIB054 3500 mg (Delayed Start) DBE Period: BIIB054 250 mg (Early Start) DBE Period: BIIB054 1250 mg (Early Start) DBE Period: BIIB054 3500 mg (Early Start)
Hide Arm/Group Description Participants received BIIB054-matching placebo, intravenous (IV) infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period. Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period. Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period. Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period. Participants received BIIB054 250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received placebo in the PC period were included in this arm. Participants received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received placebo in the PC period were included in this arm. Participants received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received placebo in the PC period were included in this arm. Participants received BIIB054 250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received BIIB054 250 mg in the PC period were included in this arm. Participants received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received BIIB054 1250 mg in the PC period were included in this arm. Participants received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received BIIB054 3500 mg in the PC period were included in this arm.
Period Title: PC Period: Up to Year 1
Started 100 55 102 100 0 0 0 0 0 0
Completed 96 53 100 96 0 0 0 0 0 0
Not Completed 4 2 2 4 0 0 0 0 0 0
Reason Not Completed
Adverse Event             1             0             2             0             0             0             0             0             0             0
Consent Withdrawn             3             2             0             4             0             0             0             0             0             0
Period Title: DBE Period:Year 2 to EOS (Up to 3 Years)
Started [1] 0 0 0 0 20 37 39 52 100 96
Number of Participants Dosed 0 0 0 0 20 37 39 52 100 94
Completed 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 20 37 39 52 100 96
Reason Not Completed
Adverse Event             0             0             0             0             1             0             0             1             0             2
Consent Withdrawn             0             0             0             0             1             0             0             1             3             2
Investigator Decision             0             0             0             0             0             1             0             0             0             0
Death             0             0             0             0             0             0             0             0             0             1
Study Terminated by Sponsor             0             0             0             0             17             36             39             48             94             91
Other             0             0             0             0             1             0             0             2             3             0
[1]
Out of 345 participants who completed the PC Period, only 344 entered the DBE Period.
Arm/Group Title PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start) Total
Hide Arm/Group Description Participants received BIIB054-matching placebo, intravenous (IV) infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period. Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period. Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period. Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period. Total of all reporting groups
Overall Number of Baseline Participants 100 55 102 100 357
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 100 participants 55 participants 102 participants 100 participants 357 participants
61.0  (8.39) 61.3  (9.24) 59.2  (8.48) 59.3  (9.92) 60.1  (9.01)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 55 participants 102 participants 100 participants 357 participants
Female
28
  28.0%
16
  29.1%
29
  28.4%
34
  34.0%
107
  30.0%
Male
72
  72.0%
39
  70.9%
73
  71.6%
66
  66.0%
250
  70.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 55 participants 102 participants 100 participants 357 participants
Hispanic or Latino
3
   3.0%
1
   1.8%
1
   1.0%
6
   6.0%
11
   3.1%
Not Hispanic or Latino
96
  96.0%
54
  98.2%
101
  99.0%
94
  94.0%
345
  96.6%
Unknown or Not Reported
1
   1.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 55 participants 102 participants 100 participants 357 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.0%
2
   0.6%
Asian
0
   0.0%
0
   0.0%
3
   2.9%
3
   3.0%
6
   1.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
1
   1.0%
0
   0.0%
1
   0.3%
White
96
  96.0%
53
  96.4%
92
  90.2%
84
  84.0%
325
  91.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
4
   4.0%
2
   3.6%
6
   5.9%
11
  11.0%
23
   6.4%
Baseline Movement Disorder Society Sponsored Revision of the Unified PD Rating Scale Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 100 participants 55 participants 102 participants 100 participants 357 participants
31.9  (12.41) 31.9  (12.25) 32.9  (12.58) 32.6  (13.46) 32.4  (12.69)
[1]
Measure Description: 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.
Baseline MDS-UPDRS Subpart I Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 100 participants 55 participants 102 participants 100 participants 357 participants
4.3  (3.50) 3.3  (2.74) 4.8  (3.99) 4.3  (3.60) 4.3  (3.59)
[1]
Measure Description: 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.
Baseline MDS-UPDRS Subpart II Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 100 participants 55 participants 102 participants 100 participants 357 participants
5.4  (3.87) 5.0  (3.30) 5.3  (3.66) 5.5  (4.30) 5.3  (3.84)
[1]
Measure Description: MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD.
Baseline MDS-UPDRS Subpart III Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 100 participants 55 participants 102 participants 100 participants 357 participants
22.2  (9.31) 23.5  (9.38) 22.8  (8.69) 22.9  (8.86) 22.8  (8.99)
[1]
Measure Description: 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.
Baseline Total Striatum Striatal Binding Ratio (SBR)   [1] 
Mean (Standard Deviation)
Unit of measure:  Striatal binding ratio
Number Analyzed 100 participants 55 participants 102 participants 99 participants 356 participants
1.295  (0.3177) 1.409  (0.3875) 1.342  (0.3197) 1.351  (0.3495) 1.342  (0.3393)
[1]
Measure Analysis Population Description: ITT population. Number analyzed is the number of participants analyzed for this study specific baseline measure.
Baseline Total Putamen SBR   [1] 
Mean (Standard Deviation)
Unit of measure:  Striatal binding ratio
Number Analyzed 100 participants 55 participants 102 participants 99 participants 356 participants
1.255  (0.3429) 1.388  (0.4294) 1.291  (0.3269) 1.286  (0.3627) 1.295  (0.3597)
[1]
Measure Analysis Population Description: ITT population. Number analyzed is the number of participants analyzed for this study specific baseline measure.
Baseline Total Caudate SBR   [1] 
Mean (Standard Deviation)
Unit of measure:  Striatal binding ratio
Number Analyzed 100 participants 55 participants 102 participants 99 participants 356 participants
1.336  (0.3279) 1.433  (0.3751) 1.397  (0.3417) 1.416  (0.3643) 1.391  (0.3501)
[1]
Measure Analysis Population Description: ITT population. Number analyzed is the number of participants analyzed for this study specific baseline measure.
1.Primary Outcome
Title Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52
Hide Description MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). Number of participants analyzed were participants analyzed for this outcome measure.
Arm/Group Title PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start)
Hide Arm/Group Description:
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 53 29 57 51
Mean (Standard Error)
Unit of Measure: score on a scale
10.78  (1.490) 10.48  (1.951) 11.29  (1.446) 10.86  (1.518)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
Comments Change From Baseline in MDS-UPDRS Total Score at Week 52
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% confidence interval (CI), and p-value were based on a mixed model for repeated measures (MMRM) model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.8976
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-4.888 to 4.287
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
Comments Change From Baseline in MDS-UPDRS Total Score at Week 52
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.7960
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
-3.310 to 4.312
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
Comments Change From Baseline in MDS-UPDRS Total Score at Week 52
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.9695
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-3.805 to 3.956
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 72
Hide Description MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Time Frame Baseline, Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). As prespecified in the protocol, the data for the delayed start BIIB054 were pooled from Placebo/BIIB054 250/1250/3500 mg for the analysis of this outcome measure. Number of participants analyzed were participants analyzed for this outcome measure.
Arm/Group Title PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled) PC Period: Early Start BIIB054 250 mg PC Period: Early Start BIIB054 1250 mg PC Period: Early Start BIIB054 3500 mg
Hide Arm/Group Description:
Participants who received BIIB054-matching placebo in Year 1 followed by BIIB054 250 mg or 1250 mg or 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) were pooled in this arm.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 68 32 62 64
Mean (Standard Error)
Unit of Measure: score on a scale
7.11  (1.476) 6.83  (2.032) 8.66  (1.496) 6.94  (1.508)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 250 mg
Comments Change From Baseline in MDS-UPDRS Total Score at Week 72
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.9093
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-5.035 to 4.483
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 1250 mg
Comments Change From Baseline in MDS-UPDRS Total Score at Week 72
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.4327
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 1.55
Confidence Interval (2-Sided) 95%
-2.336 to 5.440
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 3500 mg
Comments Change From Baseline in MDS-UPDRS Total Score at Week 72
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.9330
Comments [Not Specified]
Method Mixed Model with repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-4.051 to 3.719
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the participant at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was defined as all participants who received at least one dose of study treatment (BIIB054).
Arm/Group Title PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled) PC Period: Early Start BIIB054 250 mg PC Period: Early Start BIIB054 1250 mg PC Period: Early Start BIIB054 3500 mg
Hide Arm/Group Description:
Participants who received BIIB054-matching placebo in Year 1 followed by BIIB054 250 mg or 1250 mg or 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) were pooled in this arm.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 96 55 102 100
Measure Type: Number
Unit of Measure: percentage of participants
AEs 77.1 85.5 89.2 93.0
SAEs 8.3 10.9 8.8 12.0
4.Secondary Outcome
Title Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96
Hide Description MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Time Frame Baseline, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). As prespecified in the protocol, the data for the delayed start BIIB054 were pooled from Placebo/BIIB054 250/1250/3500 mg for the analysis of this outcome measure. Number of participants analyzed were participants analyzed for this outcome measure.
Arm/Group Title PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled) PC Period: Early Start BIIB054 250 mg PC Period: Early Start BIIB054 1250 mg PC Period: Early Start BIIB054 3500 mg
Hide Arm/Group Description:
Participants who received BIIB054-matching placebo in Year 1 followed by BIIB054 250 mg or 1250 mg or 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) were pooled in this arm.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 67 28 62 59
Mean (Standard Error)
Unit of Measure: score on a scale
7.88  (1.616) 8.28  (2.317) 8.71  (1.628) 8.87  (1.659)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 250 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.8828
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
-5.013 to 5.825
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 1250 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.7019
Comments [Not Specified]
Method Mixed Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
-3.458 to 5.128
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 3500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.6519
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
-3.323 to 5.301
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Serum Concentration of BIIB054
Hide Description [Not Specified]
Time Frame Pre-dose and 1 hour post-dose of Baseline, Weeks 4, 8, 12, 16, 24, 32, 36, 44, 52, 60, 68, 84, 96, 120 and 144
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) population was defined as all participants in the ITT population who had at least one measurable BIIB054 concentration in serum or cerebrospinal fluid (CSF). Number analyzed is the number of participants analyzed at the specified time point.
Arm/Group Title BIIB054 250 mg BIIB054 1250 mg BIIB054 3500 mg
Hide Arm/Group Description:
Participants received BIIB054, 250 mg, IV infusion, from Day 1 up to EOS (approximately 3 years).
Participants received BIIB054, 1250 mg, IV infusion, from Day 1 up to EOS (approximately 3 years).
Participants received BIIB054, 3500 mg, IV infusion, from Day 1 up to EOS (approximately 3 years).
Overall Number of Participants Analyzed 75 139 139
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter (ug/mL)
Baseline (Pre-dose) Number Analyzed 48 participants 95 participants 92 participants
0.00  (0.000) 7.47  (51.281) 0.01  (0.065)
Baseline (1 Hour Post-dose) Number Analyzed 62 participants 121 participants 114 participants
75.02  (15.829) 374.79  (86.004) 1137.28  (335.336)
Week 4 (Pre-dose) Number Analyzed 46 participants 95 participants 91 participants
20.37  (5.004) 95.36  (27.882) 306.20  (95.257)
Week 4 (1 Hour Post-dose) Number Analyzed 47 participants 94 participants 91 participants
97.09  (19.711) 468.56  (190.589) 1354.19  (364.468)
Week 8 (Pre-dose) Number Analyzed 63 participants 125 participants 122 participants
29.73  (8.371) 169.79  (68.025) 495.79  (153.357)
Week 8 (1 Hour Post-dose) Number Analyzed 64 participants 127 participants 122 participants
103.69  (26.964) 543.91  (143.212) 1591.57  (465.798)
Week 12 (Pre-dose) Number Analyzed 50 participants 97 participants 96 participants
36.76  (11.830) 195.16  (51.020) 580.43  (185.761)
Week 12 (1 Hour Post-dose) Number Analyzed 54 participants 99 participants 97 participants
112.61  (27.378) 569.41  (141.250) 1632.29  (459.839)
Week 16 (Pre-dose) Number Analyzed 51 participants 99 participants 98 participants
40.82  (11.421) 201.33  (73.451) 642.06  (194.288)
Week 16 (1 Hour Post-dose) Number Analyzed 50 participants 99 participants 98 participants
117.08  (27.401) 614.85  (186.892) 1739.98  (506.346)
Week 24 (Pre-dose) Number Analyzed 54 participants 98 participants 94 participants
43.31  (12.906) 235.69  (84.454) 724.60  (228.295)
Week 24 (1 Hour Post-dose) Number Analyzed 46 participants 90 participants 87 participants
125.79  (36.695) 664.26  (209.251) 1867.92  (470.283)
Week 32 (Pre-dose) Number Analyzed 11 participants 19 participants 24 participants
42.69  (13.486) 260.35  (104.397) 772.75  (299.703)
Week 32 (1 Hour Post-dose) Number Analyzed 15 participants 25 participants 28 participants
139.00  (34.758) 626.16  (164.497) 1985.71  (497.545)
Week 36 (Pre-dose) Number Analyzed 51 participants 100 participants 96 participants
45.77  (11.867) 262.80  (85.052) 819.83  (328.774)
Week 36 (1 Hour Post-dose) Number Analyzed 51 participants 100 participants 95 participants
123.67  (29.536) 665.60  (145.235) 1916.84  (543.373)
Week 44 (Pre-dose) Number Analyzed 3 participants 5 participants 7 participants
58.17  (22.774) 280.40  (116.590) 858.43  (349.573)
Week 44 (1 Hour Post-dose) Number Analyzed 3 participants 5 participants 8 participants
143.33  (41.004) 582.40  (194.431) 2066.25  (579.555)
Week 52 (Pre-dose) Number Analyzed 49 participants 98 participants 82 participants
46.70  (19.343) 232.08  (87.529) 787.35  (341.229)
Week 52 (1 Hour Post-dose) Number Analyzed 35 participants 74 participants 64 participants
114.59  (25.913) 645.36  (264.270) 1920.78  (479.511)
Week 60 (Pre-dose) Number Analyzed 42 participants 86 participants 84 participants
43.41  (15.973) 254.52  (88.446) 724.77  (314.854)
Week 60 (1 Hour Post-dose) Number Analyzed 41 participants 83 participants 80 participants
122.55  (29.374) 657.94  (149.654) 1905.43  (494.136)
Week 68 (Pre-dose) Number Analyzed 2 participants 3 participants 2 participants
706.25  (966.969) 202.33  (34.210) 1362.50  (533.866)
Week 68 (1 Hour Post-dose) Number Analyzed 2 participants 3 participants 2 participants
171.50  (44.548) 576.33  (85.290) 2305.00  (1025.305)
Week 84 (Pre-dose) Number Analyzed 28 participants 50 participants 42 participants
47.00  (15.535) 255.54  (81.407) 746.43  (249.770)
Week 84 (1 Hour Post-dose) Number Analyzed 38 participants 60 participants 52 participants
134.91  (33.035) 648.62  (120.163) 1942.02  (501.095)
Week 96 (Pre-dose) Number Analyzed 11 participants 18 participants 16 participants
41.25  (15.345) 274.56  (71.718) 654.70  (262.926)
Week 96 (1 Hour Post-dose) Number Analyzed 10 participants 20 participants 16 participants
122.00  (29.527) 682.30  (123.653) 1822.50  (475.682)
Week 120 (Pre-dose) Number Analyzed 6 participants 6 participants 7 participants
34.98  (12.042) 279.00  (99.499) 727.29  (116.793)
Week 120 (1 Hour Post-dose) Number Analyzed 6 participants 6 participants 7 participants
119.67  (15.629) 769.83  (279.182) 1717.14  (320.037)
Week 144 (Pre-dose) Number Analyzed 0 participants 1 participants 0 participants
365.00 [1]   (NA)
Week 144 (1 Hour Post-dose) Number Analyzed 0 participants 1 participants 0 participants
721.00 [1]   (NA)
[1]
NA: Standard Deviation was not determinable.
6.Secondary Outcome
Title Change From Baseline in MDS-UPDRS Subpart I Score at Week 52
Hide Description MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). Number of participants analyzed were participants analyzed for this outcome measure.
Arm/Group Title PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start)
Hide Arm/Group Description:
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 53 29 57 51
Mean (Standard Error)
Unit of Measure: score on a scale
1.43  (0.436) 0.90  (0.570) 1.56  (0.423) 1.65  (0.446)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
Comments Change from Baseline in MDS-UPDRS Subpart I Score at Week 52
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.4327
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.53
Confidence Interval (2-Sided) 95%
-1.851 to 0.794
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
Comments Change from Baseline in MDS-UPDRS Subpart I Score at Week 52
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.8155
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-0.965 to 1.225
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
Comments Change from Baseline in MDS-UPDRS Subpart I Score at Week 52
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.7015
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
-0.899 to 1.334
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96
Hide Description MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Time Frame Baseline, Weeks 72 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). As prespecified in the protocol, the data for the delayed start BIIB054 were pooled from Placebo/BIIB054 250/1250/3500 mg for the analysis of this outcome measure. Number analyzed is the number of participants analyzed at the specified time point.
Arm/Group Title PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled) PC Period: Early Start BIIB054 250 mg PC Period: Early Start BIIB054 1250 mg PC Period: Early Start BIIB054 3500 mg
Hide Arm/Group Description:
Participants who received BIIB054-matching placebo in Year 1 followed by BIIB054 250 mg or 1250 mg or 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) were pooled in this arm.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 100 55 102 100
Mean (Standard Error)
Unit of Measure: score on a scale
Change from Baseline at Week 72 Number Analyzed 68 participants 32 participants 62 participants 64 participants
1.65  (0.395) 0.61  (0.538) 1.73  (0.402) 1.63  (0.405)
Change from Baseline at Week 96 Number Analyzed 67 participants 28 participants 62 participants 59 participants
1.95  (0.398) 1.69  (0.568) 1.93  (0.403) 1.72  (0.414)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 250 mg
Comments Change from Baseline in MDS-UPDRS Subpart I Score at Week 72
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.1038
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -1.03
Confidence Interval (2-Sided) 95%
-2.276 to 0.213
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 1250 mg
Comments Change from Baseline in MDS-UPDRS Subpart I Score at Week 72
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.8689
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.933 to 1.103
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 3500 mg
Comments Change from Baseline in MDS-UPDRS Subpart I Score at Week 72
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.9820
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-1.026 to 1.003
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 250 mg
Comments Change from Baseline in MDS-UPDRS Subpart I Score at Week 96
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.6930
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-1.563 to 1.040
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 1250 mg
Comments Change from Baseline in MDS-UPDRS Subpart I Score at Week 96
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.9606
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-1.053 to 1.001
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 3500 mg
Comments Change from Baseline in MDS-UPDRS Subpart I Score at Week 96
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.6512
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-1.269 to 0.794
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in MDS-UPDRS Subpart II Score at Week 52
Hide Description MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). Number of participants analyzed were participants analyzed for this outcome measure.
Arm/Group Title PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start)
Hide Arm/Group Description:
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 54 29 58 51
Mean (Standard Error)
Unit of Measure: score on a scale
3.17  (0.473) 2.72  (0.621) 3.16  (0.460) 3.01  (0.486)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
Comments Change from Baseline in MDS-UPDRS Subpart II Score at Week 52
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.5497
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-1.889 to 1.007
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
Comments Change from Baseline in MDS-UPDRS Subpart II Score at Week 52
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.9980
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-1.200 to 1.197
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
Comments Change from Baseline in MDS-UPDRS Subpart II Score at Week 52
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.8069
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-1.374 to 1.070
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96
Hide Description MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Time Frame Baseline, Weeks 72 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). As prespecified in the protocol, the data for the delayed start BIIB054 were pooled from (Placebo/BIIB054 250/1250/3500 mg) for the analysis of this outcome measure. Number analyzed is the number of participants analyzed at the specified time point.
Arm/Group Title PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled) PC Period: Early Start BIIB054 250 mg PC Period: Early Start BIIB054 1250 mg PC Period: Early Start BIIB054 3500 mg
Hide Arm/Group Description:
Participants who received BIIB054-matching placebo in Year 1 followed by BIIB054 250 mg or 1250 mg or 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) were pooled in this arm.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 100 55 102 100
Mean (Standard Error)
Unit of Measure: score on a scale
Change from Baseline at Week 72 Number Analyzed 69 participants 33 participants 62 participants 64 participants
1.83  (0.491) 1.62  (0.672) 2.36  (0.497) 1.68  (0.503)
Change from Baseline at Week 96 Number Analyzed 67 participants 28 participants 62 participants 60 participants
1.87  (0.529) 1.33  (0.762) 2.39  (0.533) 2.22  (0.541)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 250 mg
Comments Change from Baseline in MDS-UPDRS Subpart II Score at Week 72
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.7968
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-1.786 to 1.372
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 1250 mg
Comments Change from Baseline in MDS-UPDRS Subpart II Score at Week 72
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.4211
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
-0.766 to 1.827
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 3500 mg
Comments Change from Baseline in MDS-UPDRS Subpart II Score at Week 72
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.8166
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-1.448 to 1.143
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 250 mg
Comments Change from Baseline in MDS-UPDRS Subpart II Score at Week 96
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.5535
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.53
Confidence Interval (2-Sided) 95%
-2.310 to 1.240
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 1250 mg
Comments Change from Baseline in MDS-UPDRS Subpart II Score at Week 96
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.4654
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
-0.881 to 1.922
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 3500 mg
Comments Change from Baseline in MDS-UPDRS Subpart II Score at Week 96
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.6184
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
-1.051 to 1.763
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in MDS-UPDRS Subpart III Score at Week 52
Hide Description MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). Number of participants analyzed were participants analyzed for this outcome measure.
Arm/Group Title PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start)
Hide Arm/Group Description:
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 53 29 58 51
Mean (Standard Error)
Unit of Measure: score on a scale
6.10  (1.083) 6.69  (1.419) 6.76  (1.046) 6.20  (1.104)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
Comments Change from Baseline in MDS-UPDRS Subpart III Score at Week 52
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.7274
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
-2.742 to 3.925
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
Comments Change from Baseline in MDS-UPDRS Subpart III Score at Week 52
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.6385
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
-2.094 to 3.411
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
Comments Change from Baseline in MDS-UPDRS Subpart III Score at Week 52
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, baseline MDS-UPDRS score, baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.9467
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-2.718 to 2.910
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96
Hide Description MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Time Frame Baseline, Weeks 72 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). As prespecified in the protocol, the data for the delayed start BIIB054 were pooled from (Placebo/BIIB054 250/1250/3500 mg) for the analysis of this outcome measure. Number analyzed is the number of participants analyzed at the specified time point.
Arm/Group Title PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled) PC Period: Early Start BIIB054 250 mg PC Period: Early Start BIIB054 1250 mg PC Period: Early Start BIIB054 3500 mg
Hide Arm/Group Description:
Participants who received BIIB054-matching placebo in Year 1 followed by BIIB054 250 mg or 1250 mg or 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) were pooled in this arm.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 100 55 102 100
Mean (Standard Error)
Unit of Measure: score on a scale
Change from Baseline at Week 72 Number Analyzed 68 participants 32 participants 62 participants 64 participants
3.64  (1.027) 4.48  (1.404) 4.49  (1.038) 3.69  (1.048)
Change from Baseline at Week 96 Number Analyzed 67 participants 28 participants 62 participants 60 participants
4.49  (1.174) 5.14  (1.679) 4.39  (1.180) 5.17  (1.201)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 250 mg
Comments Change from Baseline in MDS-UPDRS Subpart III Score at Week 72
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.6112
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
-2.423 to 4.114
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 1250 mg
Comments Change from Baseline in MDS-UPDRS Subpart III Score at Week 72
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.5270
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
-1.806 to 3.520
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 3500 mg
Comments Change from Baseline in MDS-UPDRS Subpart III Score at Week 72
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.9673
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-2.608 to 2.719
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 250 mg
Comments Change from Baseline in MDS-UPDRS Subpart III Score at Week 96
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.7455
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
-3.274 to 4.569
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 1250 mg
Comments Change from Baseline in MDS-UPDRS Subpart III Score at Week 96
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.9506
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-3.192 to 2.997
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled), PC Period: Early Start BIIB054 3500 mg
Comments Change from Baseline in MDS-UPDRS Subpart III Score at Week 96
Type of Statistical Test Superiority
Comments Adjusted mean, difference with delayed start group, 95% CI, and p-value were based on an MMRM model, with change from baseline in MDS-UPDRS score as dependent variable and with fixed effects of treatment group, time, treatment group-by-time interaction, region, PD subtype, prior use of PD medication, corresponding baseline MDS-UPDRS score, corresponding baseline MDS-UPDRS by time interaction, baseline striatum SBR values and baseline striatum SBR value by time interaction.
Statistical Test of Hypothesis P-Value 0.6643
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
-2.422 to 3.794
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in Striatal Binding Ratio (SBR) in the Putamen as Measured by Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter (DaT) at Week 52
Hide Description SBR in the putamen as measured by SPECT imaging of the dopamine transporter (DaT) with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacodynamic population was defined as a subset of the ITT population with at least 1 post-baseline pharmacodynamic measurement.
Arm/Group Title PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start)
Hide Arm/Group Description:
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 91 52 97 84
Mean (Standard Error)
Unit of Measure: striatal binding ratio
-0.093  (0.0151) -0.098  (0.0199) -0.102  (0.0146) -0.125  (0.0155)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in DaT/SPECT parameter as dependent variable and with fixed effects of treatment group, region, time, treatment group-by-time interaction, baseline MDS-UPDRS part I+II+III total score, baseline MDS-UPDRS part I+II+III total score by time interaction, baseline DaT/SPECT values and baseline DaT/SPECT by time interaction.
Statistical Test of Hypothesis P-Value 0.8274
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.005
Confidence Interval (2-Sided) 95%
-0.0548 to 0.0438
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in DaT/SPECT parameter as dependent variable and with fixed effects of treatment group, region, time, treatment group-by-time interaction, baseline MDS-UPDRS part I+II+III total score, baseline MDS-UPDRS part I+II+III total score by time interaction, baseline DaT/SPECT values and baseline DaT/SPECT by time interaction.
Statistical Test of Hypothesis P-Value 0.6671
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.009
Confidence Interval (2-Sided) 95%
-0.0504 to 0.0323
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in DaT/SPECT parameter as dependent variable and with fixed effects of treatment group, region, time, treatment group-by-time interaction, baseline MDS-UPDRS part I+II+III total score, baseline MDS-UPDRS part I+II+III total score by time interaction, baseline DaT/SPECT values and baseline DaT/SPECT by time interaction.
Statistical Test of Hypothesis P-Value 0.1313
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.033
Confidence Interval (2-Sided) 95%
-0.0751 to 0.0098
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52
Hide Description SBR in the striatum as measured by SPECT imaging of the DaT with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacodynamic population was defined as a subset of the ITT population with at least 1 post-baseline pharmacodynamic measurement.
Arm/Group Title PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start)
Hide Arm/Group Description:
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 91 52 97 84
Mean (Standard Error)
Unit of Measure: striatal binding ratio
-0.081  (0.0145) -0.090  (0.0191) -0.081  (0.0140) -0.108  (0.0148)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in DaT/SPECT parameter as dependent variable and with fixed effects of treatment group, region, time, treatment group-by-time interaction, baseline MDS-UPDRS part I+II+III total score, baseline MDS-UPDRS part I+II+III total score by time interaction, baseline DaT/SPECT values and baseline DaT/SPECT by time interaction.
Statistical Test of Hypothesis P-Value 0.7079
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.009
Confidence Interval (2-Sided) 95%
-0.0562 to 0.0382
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in DaT/SPECT parameter as dependent variable and with fixed effects of treatment group, region, time, treatment group-by-time interaction, baseline MDS-UPDRS part I+II+III total score, baseline MDS-UPDRS part I+II+III total score by time interaction, baseline DaT/SPECT values and baseline DaT/SPECT by time interaction.
Statistical Test of Hypothesis P-Value 0.9835
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.000
Confidence Interval (2-Sided) 95%
-0.0400 to 0.0392
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in DaT/SPECT parameter as dependent variable and with fixed effects of treatment group, region, time, treatment group-by-time interaction, baseline MDS-UPDRS part I+II+III total score, baseline MDS-UPDRS part I+II+III total score by time interaction, baseline DaT/SPECT values and baseline DaT/SPECT by time interaction.
Statistical Test of Hypothesis P-Value 0.1869
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.027
Confidence Interval (2-Sided) 95%
-0.0682 to 0.0134
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52
Hide Description SBR in the caudate as measured by SPECT imaging of the DaT with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacodynamic population was defined as a subset of the ITT population with at least 1 post-baseline pharmacodynamic measurement.
Arm/Group Title PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start)
Hide Arm/Group Description:
Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 91 52 97 84
Mean (Standard Error)
Unit of Measure: striatal binding ratio
-0.067  (0.0166) -0.075  (0.0219) -0.060  (0.0161) -0.089  (0.0171)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 250 mg (Early Start)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in DaT/SPECT parameter as dependent variable and with fixed effects of treatment group, region, time, treatment group-by-time interaction, baseline MDS-UPDRS part I+II+III total score, baseline MDS-UPDRS part I+II+III total score by time interaction, baseline DaT/SPECT values and baseline DaT/SPECT by time interaction.
Statistical Test of Hypothesis P-Value 0.7585
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.008
Confidence Interval (2-Sided) 95%
-0.0625 to 0.0456
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 1250 mg (Early Start)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in DaT/SPECT parameter as dependent variable and with fixed effects of treatment group, region, time, treatment group-by-time interaction, baseline MDS-UPDRS part I+II+III total score, baseline MDS-UPDRS part I+II+III total score by time interaction, baseline DaT/SPECT values and baseline DaT/SPECT by time interaction.
Statistical Test of Hypothesis P-Value 0.7808
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.006
Confidence Interval (2-Sided) 95%
-0.0391 to 0.0520
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PC Period: Placebo, PC Period: BIIB054 3500 mg (Early Start)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Adjusted mean, difference with placebo, 95% CI, and p-value were based on an MMRM model, with change from baseline in DaT/SPECT parameter as dependent variable and with fixed effects of treatment group, region, time, treatment group-by-time interaction, baseline MDS-UPDRS part I+II+III total score, baseline MDS-UPDRS part I+II+III total score by time interaction, baseline DaT/SPECT values and baseline DaT/SPECT by time interaction.
Statistical Test of Hypothesis P-Value 0.3532
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.022
Confidence Interval (2-Sided) 95%
-0.0691 to 0.0248
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants With Anti-BIIB054 Antibodies in the Serum
Hide Description [Not Specified]
Time Frame Up to Week 144
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population for immunogenicity was defined as all participants in the safety population. As prespecified in the protocol, the data for the delayed start BIIB054 were pooled from Placebo/BIIB054 250/1250/3500 mg for the analysis of this outcome measure.
Arm/Group Title PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled) PC Period: Early Start BIIB054 250 mg PC Period: Early Start BIIB054 1250 mg PC Period: Early Start BIIB054 3500 mg
Hide Arm/Group Description:
Participants who received BIIB054-matching placebo in Year 1 followed by BIIB054 250 mg or 1250 mg or 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) were pooled in this arm.
Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period.
Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in PC Period.
Overall Number of Participants Analyzed 96 55 100 99
Measure Type: Number
Unit of Measure: percentage of participants
0 1.8 0 0
Time Frame Up to 3 years
Adverse Event Reporting Description Safety Population included all participants who received at least one dose of the study treatment (BIIB054 250 mg, 1250 mg, 3500 mg).
 
Arm/Group Title PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start) DBE Period: Placebo to BIIB054 250 mg (Delayed Start) DBE Period: Placebo to BIIB054 1250 mg (Delayed Start) DBE Period: Placebo to BIIB054 3500 mg (Delayed Start) DBE Period: BIIB054 250 mg (Early Start) DBE Period: BIIB054 1250 mg (Early Start) DBE Period: BIIB054 3500 mg (Early Start)
Hide Arm/Group Description Participants received BIIB054-matching placebo, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period. Participants received BIIB054, 250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period. Participants received BIIB054, 1250 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period. Participants received BIIB054, 3500 mg, IV infusion, on Day 1 and then every 4 weeks for Year 1 in the PC Period. Participants received BIIB054 250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received placebo in the PC period were included in this arm. Participants received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received placebo in the PC period were included in this arm. Participants received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received placebo in the PC period were included in this arm. Participants received BIIB054 250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received BIIB054 250 mg in the PC period were included in this arm. Participants received BIIB054 1250 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received BIIB054 1250 mg in the PC period were included in this arm. Participants received BIIB054 3500 mg, IV infusion from Year 2 up to EOS (approximately 3 years) in the DBE Period. Participants who received BIIB054 3500 mg in the PC period were included in this arm.
All-Cause Mortality
PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start) DBE Period: Placebo to BIIB054 250 mg (Delayed Start) DBE Period: Placebo to BIIB054 1250 mg (Delayed Start) DBE Period: Placebo to BIIB054 3500 mg (Delayed Start) DBE Period: BIIB054 250 mg (Early Start) DBE Period: BIIB054 1250 mg (Early Start) DBE Period: BIIB054 3500 mg (Early Start)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/100 (0.00%)   0/55 (0.00%)   0/102 (0.00%)   0/100 (0.00%)   0/20 (0.00%)   0/37 (0.00%)   0/39 (0.00%)   0/52 (0.00%)   0/100 (0.00%)   1/94 (1.06%) 
Hide Serious Adverse Events
PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start) DBE Period: Placebo to BIIB054 250 mg (Delayed Start) DBE Period: Placebo to BIIB054 1250 mg (Delayed Start) DBE Period: Placebo to BIIB054 3500 mg (Delayed Start) DBE Period: BIIB054 250 mg (Early Start) DBE Period: BIIB054 1250 mg (Early Start) DBE Period: BIIB054 3500 mg (Early Start)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/100 (7.00%)   4/55 (7.27%)   4/102 (3.92%)   6/100 (6.00%)   2/20 (10.00%)   3/37 (8.11%)   3/39 (7.69%)   3/52 (5.77%)   5/100 (5.00%)   7/94 (7.45%) 
Blood and lymphatic system disorders                     
Monoclonal B-cell lymphocytosis  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Cardiac disorders                     
Bradycardia  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Myocardial infarction  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Palpitations  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Pericarditis  1  0/100 (0.00%)  0/55 (0.00%)  1/102 (0.98%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Sinus bradycardia  1  0/100 (0.00%)  1/55 (1.82%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Gastrointestinal disorders                     
Small intestinal obstruction  1  1/100 (1.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
General disorders                     
Impaired healing  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Hepatobiliary disorders                     
Hepatitis toxic  1  1/100 (1.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Immune system disorders                     
Anaphylactic reaction  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  1/37 (2.70%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Infections and infestations                     
COVID-19  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  1/37 (2.70%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
COVID-19 pneumonia  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  1/37 (2.70%)  0/39 (0.00%)  0/52 (0.00%)  1/100 (1.00%)  0/94 (0.00%) 
Gastroenteritis  1  1/100 (1.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Gastroenteritis viral  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  1/100 (1.00%)  0/94 (0.00%) 
Perirectal abscess  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Viral infection  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Injury, poisoning and procedural complications                     
Arthropod sting  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  1/37 (2.70%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Fall  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  1/52 (1.92%)  0/100 (0.00%)  0/94 (0.00%) 
Femur fracture  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Jaw fracture  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  1/52 (1.92%)  0/100 (0.00%)  0/94 (0.00%) 
Muscle strain  1  1/100 (1.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Pelvic fracture  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Post lumbar puncture syndrome  1  1/100 (1.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Road traffic accident  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Spinal compression fracture  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Ulna fracture  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Musculoskeletal and connective tissue disorders                     
Arthritis  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Back pain  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Lumbar spinal stenosis  1  0/100 (0.00%)  1/55 (1.82%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Musculoskeletal chest pain  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Osteoarthritis  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  1/39 (2.56%)  0/52 (0.00%)  1/100 (1.00%)  0/94 (0.00%) 
Rotator cuff syndrome  1  0/100 (0.00%)  0/55 (0.00%)  1/102 (0.98%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  1/52 (1.92%)  0/100 (0.00%)  0/94 (0.00%) 
Spinal stenosis  1  0/100 (0.00%)  1/55 (1.82%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Spondylolisthesis  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  1/39 (2.56%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                     
Basal cell carcinoma  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  1/100 (1.00%)  0/94 (0.00%) 
Glioblastoma  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Invasive lobular breast carcinoma  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  1/37 (2.70%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Prostate cancer  1  0/100 (0.00%)  1/55 (1.82%)  0/102 (0.00%)  1/100 (1.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Nervous system disorders                     
Intracranial mass  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Sciatica  1  1/100 (1.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Transient ischaemic attack  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  1/52 (1.92%)  1/100 (1.00%)  0/94 (0.00%) 
Psychiatric disorders                     
Depression  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/20 (0.00%)  0/37 (0.00%)  1/39 (2.56%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Suicidal ideation  1  0/100 (0.00%)  0/55 (0.00%)  1/102 (0.98%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Renal and urinary disorders                     
Nephrolithiasis  1  0/100 (0.00%)  0/55 (0.00%)  1/102 (0.98%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Reproductive system and breast disorders                     
Benign prostatic hyperplasia  1  1/100 (1.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Respiratory, thoracic and mediastinal disorders                     
Acute respiratory failure  1  1/100 (1.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
1
Term from vocabulary, MedDRA Version 23.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PC Period: Placebo PC Period: BIIB054 250 mg (Early Start) PC Period: BIIB054 1250 mg (Early Start) PC Period: BIIB054 3500 mg (Early Start) DBE Period: Placebo to BIIB054 250 mg (Delayed Start) DBE Period: Placebo to BIIB054 1250 mg (Delayed Start) DBE Period: Placebo to BIIB054 3500 mg (Delayed Start) DBE Period: BIIB054 250 mg (Early Start) DBE Period: BIIB054 1250 mg (Early Start) DBE Period: BIIB054 3500 mg (Early Start)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   58/100 (58.00%)   32/55 (58.18%)   61/102 (59.80%)   63/100 (63.00%)   16/20 (80.00%)   22/37 (59.46%)   22/39 (56.41%)   25/52 (48.08%)   51/100 (51.00%)   56/94 (59.57%) 
Blood and lymphatic system disorders                     
Anaemia  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  1/37 (2.70%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Coagulopathy  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Cardiac disorders                     
Ventricular extrasystoles  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Ear and labyrinth disorders                     
Paraesthesia ear  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Vertigo  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  1/100 (1.00%)  0/94 (0.00%) 
Gastrointestinal disorders                     
Constipation  1  5/100 (5.00%)  3/55 (5.45%)  5/102 (4.90%)  6/100 (6.00%)  1/20 (5.00%)  2/37 (5.41%)  1/39 (2.56%)  1/52 (1.92%)  4/100 (4.00%)  7/94 (7.45%) 
Diarrhoea  1  4/100 (4.00%)  5/55 (9.09%)  5/102 (4.90%)  6/100 (6.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  1/52 (1.92%)  2/100 (2.00%)  3/94 (3.19%) 
Nausea  1  6/100 (6.00%)  1/55 (1.82%)  6/102 (5.88%)  6/100 (6.00%)  1/20 (5.00%)  2/37 (5.41%)  4/39 (10.26%)  2/52 (3.85%)  4/100 (4.00%)  7/94 (7.45%) 
Dysphagia  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  1/39 (2.56%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Gastrooesophageal reflux disease  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  1/39 (2.56%)  0/52 (0.00%)  2/100 (2.00%)  0/94 (0.00%) 
Haemorrhoids  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  1/37 (2.70%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Toothache  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  2/39 (5.13%)  1/52 (1.92%)  0/100 (0.00%)  3/94 (3.19%) 
General disorders                     
Fatigue  1  5/100 (5.00%)  2/55 (3.64%)  3/102 (2.94%)  9/100 (9.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  1/52 (1.92%)  4/100 (4.00%)  5/94 (5.32%) 
Asthenia  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Infections and infestations                     
COVID-19  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  2/37 (5.41%)  2/39 (5.13%)  0/52 (0.00%)  6/100 (6.00%)  3/94 (3.19%) 
Influenza  1  3/100 (3.00%)  1/55 (1.82%)  7/102 (6.86%)  1/100 (1.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Nasopharyngitis  1  12/100 (12.00%)  10/55 (18.18%)  10/102 (9.80%)  13/100 (13.00%)  2/20 (10.00%)  0/37 (0.00%)  0/39 (0.00%)  2/52 (3.85%)  4/100 (4.00%)  5/94 (5.32%) 
Upper respiratory tract infection  1  3/100 (3.00%)  2/55 (3.64%)  6/102 (5.88%)  7/100 (7.00%)  0/20 (0.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Urinary tract infection  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  2/20 (10.00%)  2/37 (5.41%)  1/39 (2.56%)  3/52 (5.77%)  2/100 (2.00%)  2/94 (2.13%) 
Bronchitis  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  2/37 (5.41%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Tooth infection  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  1/52 (1.92%)  1/100 (1.00%)  1/94 (1.06%) 
Injury, poisoning and procedural complications                     
Fall  1  5/100 (5.00%)  5/55 (9.09%)  6/102 (5.88%)  14/100 (14.00%)  2/20 (10.00%)  2/37 (5.41%)  3/39 (7.69%)  10/52 (19.23%)  16/100 (16.00%)  16/94 (17.02%) 
Ligament rupture  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Procedural pain  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  2/20 (10.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  1/94 (1.06%) 
Skin laceration  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  3/52 (5.77%)  1/100 (1.00%)  1/94 (1.06%) 
Investigations                     
Blood cholesterol increased  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Blood glucose increased  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  1/100 (1.00%)  0/94 (0.00%) 
Transaminases increased  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Weight decreased  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Metabolism and nutrition disorders                     
Calcium deficiency  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Decreased appetite  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Musculoskeletal and connective tissue disorders                     
Arthralgia  1  7/100 (7.00%)  5/55 (9.09%)  9/102 (8.82%)  11/100 (11.00%)  1/20 (5.00%)  4/37 (10.81%)  3/39 (7.69%)  3/52 (5.77%)  7/100 (7.00%)  2/94 (2.13%) 
Back pain  1  8/100 (8.00%)  3/55 (5.45%)  8/102 (7.84%)  13/100 (13.00%)  0/20 (0.00%)  4/37 (10.81%)  6/39 (15.38%)  5/52 (9.62%)  5/100 (5.00%)  8/94 (8.51%) 
Musculoskeletal stiffness  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  1/37 (2.70%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Pain in extremity  1  2/100 (2.00%)  4/55 (7.27%)  5/102 (4.90%)  1/100 (1.00%)  0/20 (0.00%)  1/37 (2.70%)  2/39 (5.13%)  2/52 (3.85%)  2/100 (2.00%)  2/94 (2.13%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                     
Benign neoplasm of skin  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  1/52 (1.92%)  0/100 (0.00%)  1/94 (1.06%) 
Nervous system disorders                     
Dizziness  1  3/100 (3.00%)  4/55 (7.27%)  9/102 (8.82%)  6/100 (6.00%)  0/20 (0.00%)  2/37 (5.41%)  2/39 (5.13%)  1/52 (1.92%)  4/100 (4.00%)  4/94 (4.26%) 
Headache  1  18/100 (18.00%)  6/55 (10.91%)  19/102 (18.63%)  21/100 (21.00%)  3/20 (15.00%)  5/37 (13.51%)  5/39 (12.82%)  1/52 (1.92%)  7/100 (7.00%)  12/94 (12.77%) 
Parkinson's disease  1  1/100 (1.00%)  4/55 (7.27%)  9/102 (8.82%)  8/100 (8.00%)  1/20 (5.00%)  1/37 (2.70%)  0/39 (0.00%)  1/52 (1.92%)  0/100 (0.00%)  0/94 (0.00%) 
Paraesthesia  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  1/100 (1.00%)  2/94 (2.13%) 
Restless legs syndrome  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Somnolence  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  1/39 (2.56%)  0/52 (0.00%)  1/100 (1.00%)  1/94 (1.06%) 
Transient ischaemic attack  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Psychiatric disorders                     
Anxiety  1  4/100 (4.00%)  0/55 (0.00%)  9/102 (8.82%)  5/100 (5.00%)  1/20 (5.00%)  1/37 (2.70%)  2/39 (5.13%)  1/52 (1.92%)  1/100 (1.00%)  4/94 (4.26%) 
Depression  1  1/100 (1.00%)  3/55 (5.45%)  3/102 (2.94%)  3/100 (3.00%)  1/20 (5.00%)  2/37 (5.41%)  0/39 (0.00%)  0/52 (0.00%)  2/100 (2.00%)  4/94 (4.26%) 
Insomnia  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  4/37 (10.81%)  2/39 (5.13%)  3/52 (5.77%)  2/100 (2.00%)  2/94 (2.13%) 
Reproductive system and breast disorders                     
Erectile dysfunction  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  0/37 (0.00%)  2/39 (5.13%)  0/52 (0.00%)  1/100 (1.00%)  1/94 (1.06%) 
Respiratory, thoracic and mediastinal disorders                     
Cough  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  2/37 (5.41%)  1/39 (2.56%)  1/52 (1.92%)  1/100 (1.00%)  2/94 (2.13%) 
Oropharyngeal pain  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  1/37 (2.70%)  1/39 (2.56%)  0/52 (0.00%)  2/100 (2.00%)  1/94 (1.06%) 
Atelectasis  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Diaphragmatic paralysis  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Hypoxia  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Skin and subcutaneous tissue disorders                     
Rash  1  3/100 (3.00%)  1/55 (1.82%)  0/102 (0.00%)  5/100 (5.00%)  0/20 (0.00%)  0/37 (0.00%)  3/39 (7.69%)  0/52 (0.00%)  0/100 (0.00%)  2/94 (2.13%) 
Skin irritation  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Skin ulcer  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/20 (5.00%)  0/37 (0.00%)  0/39 (0.00%)  0/52 (0.00%)  0/100 (0.00%)  0/94 (0.00%) 
Vascular disorders                     
Hypertension  1  0/100 (0.00%)  0/55 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/20 (0.00%)  2/37 (5.41%)  2/39 (5.13%)  0/52 (0.00%)  5/100 (5.00%)  2/94 (2.13%) 
1
Term from vocabulary, MedDRA Version 23.1
Indicates events were collected by systematic assessment
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
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Our agreement is subject to confidentiality but generally the PI can publish, for non-commercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: US Biogen Clinical Trial Center
Organization: Biogen
Phone: 866-633-4636
EMail: clinicaltrials@biogen.com
Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT03318523    
Other Study ID Numbers: 228PD201
2016-004610-95 ( EudraCT Number )
First Submitted: October 19, 2017
First Posted: October 24, 2017
Results First Submitted: October 25, 2021
Results First Posted: November 23, 2021
Last Update Posted: February 28, 2022