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Study of BIIB092 in Participants With Progressive Supranuclear Palsy (PASSPORT)

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: NCT03068468
Recruitment Status : Terminated (251PP301(PASSPORT) primary endpoint was not met;Biogen decision to close the study early. There were no safety concerns with the PASSPORT study.)
First Posted : March 1, 2017
Results First Posted : December 21, 2020
Last Update Posted : December 21, 2020
Sponsor:
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Supranuclear Palsy, Progressive
Interventions Drug: BIIB092
Drug: Placebo
Enrollment 490
Recruitment Details Participants were enrolled at 89 investigative sites in the United States, Australia, Austria, Canada, France, Germany, Greece, Italy, Japan, Republic of Korea, Russia Federation, Spain and United Kingdom from June 01, 2017 to February 07, 2020.
Pre-assignment Details A total of 490 participants with Progressive Supranuclear Palsy disease were enrolled and randomised in the study. Of these, 486 participants received the study drug in placebo-controlled (PC) period. After completing PC period, 416 participants entered and dosed in open-label extension (OLE) period and no participants completed the study due to early termination of the study.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period) BIIB092 Late Start (OLE Period) BIIB092 Early Start (OLE Period)
Hide Arm/Group Description Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo. Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period. Late start subjects received only placebo in the placebo-controlled period and assigned to BIIB092 2000 mg IV infusion once every 4 weeks starting at Week 52 in the OLE period. Early start subjects are those who received BIIB092 2000 mg in the placebo-controlled period and assigned to BIIB092 2000 mg IV infusion once every 4 weeks starting at Week 52 in the OLE period.
Period Title: Placebo-Controlled Period
Started 166 324 0 0
Treated 165 321 0 0
Completed [1] 144 279 0 0
Not Completed 22 45 0 0
Reason Not Completed
Randomized but not Treated             1             3             0             0
Lack of Efficacy             0             1             0             0
Adverse Event             16             21             0             0
Withdrawal by Subject             3             11             0             0
Withdrawal by Parent/Guardian             1             2             0             0
Reason Not Specified             1             6             0             0
Death             0             1             0             0
[1]
Participants who completed the study PC period
Period Title: Open-Label Extension Period
Started 0 0 140 [1] 276 [2]
Completed 0 0 0 0
Not Completed 0 0 140 276
Reason Not Completed
Lack of Efficacy             0             0             1             2
Adverse Event             0             0             13             17
Withdrawal by Subject             0             0             7             20
Death             0             0             0             1
Lost to Follow-up             0             0             1             0
Failure to Meet Randomization Criteria             0             0             2             0
Withdrawal by Sponsor             0             0             115             228
Withdrawal by Parent/Guardian             0             0             0             4
Reason not Specified             0             0             1             4
[1]
4 participants did not enter OLE period.
[2]
3 participants did not enter OLE period.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period) Total
Hide Arm/Group Description Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo. Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period. Total of all reporting groups
Overall Number of Baseline Participants 165 321 486
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 165 participants 321 participants 486 participants
68.9  (6.57) 68.7  (7.02) 68.7  (6.86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 165 participants 321 participants 486 participants
Female
74
  44.8%
136
  42.4%
210
  43.2%
Male
91
  55.2%
185
  57.6%
276
  56.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 165 participants 321 participants 486 participants
Hispanic or Latino
5
   3.0%
7
   2.2%
12
   2.5%
Not Hispanic or Latino
117
  70.9%
242
  75.4%
359
  73.9%
Unknown or Not Reported
43
  26.1%
72
  22.4%
115
  23.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 165 participants 321 participants 486 participants
White
138
  83.6%
281
  87.5%
419
  86.2%
Black or African American
1
   0.6%
1
   0.3%
2
   0.4%
Asian Indian
3
   1.8%
3
   0.9%
6
   1.2%
Chinese
0
   0.0%
1
   0.3%
1
   0.2%
Japanese
16
   9.7%
23
   7.2%
39
   8.0%
Asian Other
4
   2.4%
10
   3.1%
14
   2.9%
Unknown
3
   1.8%
2
   0.6%
5
   1.0%
1.Primary Outcome
Title Change From Baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at Week 52
Hide Description The PSPRS is a quantitative measure of disability in participants with PSP. The PSPRS comprises 28 items in 6 areas. Six items are rated on a 3-point scale (0-2) and 22 are rated on a 5-point scale (0-4). The 6 areas are the History/Daily Activities, Mentation, Bulbar, Ocular Motor, Limb Motor, and Gait. The 28-item PSPRS total score ranges from 0 (normal) to 100. Fifteen items are selected to form a 15-item PSPRS and three domains are identified: Gait/Limb function, Ocular Motor, and Bulbar. The total 15-item PSPRS score ranges from 0 (normal) to 52. A positive change from baseline indicates worsening.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies number of participants who had response on Week 52.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 139 278
Mean (Standard Error)
Unit of Measure: Score on a scale
PSPRS: 28 items 10.6  (0.8) 10.4  (0.6)
PSPRS: 15 items 7.57  (0.52) 7.29  (0.38)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments 28-item:Adjusted mean for each treatment group, difference with Placebo,95% confidence interval and p-value at each time point were based on a mixed model for repeated measures model (MMRM), with change from baseline in 28-item PSPRS total score as dependent variable and with fixed effects of treatment group, time(categorical), treatment group-by-time interaction, baseline 28-item PSPRS, baseline 28-item PSPRS by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8483
Comments [Not Specified]
Method Mixed model for repeated measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-2.0 to 1.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments 15-items:Adjusted mean for each treatment group, difference with Placebo,95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in 15-item PSPRS total score as dependent variable and with fixed effects of treatment group, time(categorical), treatment groupby-time interaction, baseline 15-item PSPRS, baseline 15-item PSPRS by time interaction, baseline Color Trails 2 test(<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6503
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-1.50 to 0.94
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and Adverse Events (AEs) Leading to Discontinuation of Drug
Hide Description AEs: any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. SAEs: an event that results in death; an event that, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event); an outcome that results in a congenital anomaly/birth defect diagnosed in a child of a participant; an event that requires or prolongs inpatient hospitalization; an event that results in persistent or significant disability/incapacity.
Time Frame up to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who had received at least one dose of study treatment (BIIB092 or Placebo). Participants randomized to Placebo that received at least one dose of BIIB092 2000 mg during the placebo-controlled period will be counted in the BIIB092 2000 mg group for the safety population. Three participants who received BIIB092 in Placebo group were counted in BIIB092 200 mg group.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 162 324
Measure Type: Number
Unit of Measure: Percentage of participants
Death 4.9 4.9
SAEs 32.1 27.2
AEs 93.2 92.9
AEs Leading to Discontinuation of Drug 11.1 7.4
3.Secondary Outcome
Title Change From Baseline in Movement Disorder Society (MDS)-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II at Week 52
Hide Description The MDS-UPRDRS Part 2 includes 13 items assessing motor aspects of experiences of daily living (M-EDL) these include speech, saliva and drooling, chewing and swallowing, handwriting, doing hobbies and other activities, eating tasks, tremor, dressing, hygiene, turning in bed, getting out of bed, walking and balance, and freezing. All items have 5 responses with uniform anchors of 0= normal, 1= slight, 2= mild, 3= moderate, and 4= severe. Total score ranges from 0 to 52, higher score indicating severe conditions. A positive change from baseline indicates worsening.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies total number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 143 270
Mean (Standard Error)
Unit of Measure: Score on a scale
6.7  (0.6) 7.0  (0.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MDS-UPDRS as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline MDS-UPDRS, baseline MDS-UPDRS by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6031
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.0 to 1.7
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Clinical Global Impression of Change (CGI-C) Scale Score
Hide Description The CGI-C scale measures the change in the patient's clinical status from a specific point in time. Using a 7-point scale, ranging from 1 (very much improved) to 7 (very much worse), with a score of 4 indicating no change.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies total number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 138 271
Mean (Standard Error)
Unit of Measure: Score on a scale
5.3  (0.1) 5.2  (0.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with CGI-C as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline CGI-S, baseline CGI-S by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7743
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-0.2 to 0.1
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Progressive Supranuclear Palsy (PSP)-Cognitive Composite Battery Z-Score at Week 52
Hide Description The PSP cognitive composite battery is used to identify and characterize abnormal cognitive decline in PSP participants. The PSP cognitive composite battery includes 13 sub-tests in total: 11 tests from the RBANS (only the picture naming is excluded), letter number sequencing test, and phonemic fluency test. Three domains are identified: Memory and learning, Visual-Motor function, and Working memory and Executive. A z-score transformation is applied for each component test at each visit, and the final total composite z-score is the average of the three-domain z-scores. A z-score of 0 is equal to the estimated mean adjusted by age and is considered average for this study population. Lower values are indicative of cognitive decline. A negative change from baseline indicates worsening.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies the total number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 134 249
Mean (Standard Error)
Unit of Measure: z-score
-0.283  (0.032) -0.245  (0.024)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in PSP-cognitive composite battery as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline PSP-cognitive composite battery, baseline PSP-cognitive composite battery by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3180
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.038
Confidence Interval (2-Sided) 95%
-0.036 to 0.112
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Disease Severity (RBANS) Scale at Week 52
Hide Description The RBANS provides both a total scale score and scores for 5 different cognitive domains. Specifically, the test measures immediate memory, visuospatial/constructional ability, language, attention, and delayed memory. Scores from all subtests are aggregated into a total composite score. RBANS data were age-normed and analyzed as index scores (also referred to as standard scores), which have a mean of 100 and a standard deviation of 15. Higher scores on each sub measure and index indicate better performance. A negative change from baseline indicates worsening.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies total number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 111 222
Mean (Standard Error)
Unit of Measure: Score on a scale
-3.1  (0.7) -3.2  (0.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in RBANS as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline RBANS , baseline RBANS by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8270
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.8 to 1.4
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) Score
Hide Description The PSP-QoL is a patient-reported outcome measure developed specifically for assessing the health-related quality of life in people living with PSP. It is validated 45-item questionnaire and visual analog scale that is comprised of 2 subscales: physical health state (22 items), which covers mobility, dysarthria, dysphagia, visual disturbances, self-care, and activities of daily living, and mental health state (23 items), which covers emotional, cognitive and social functioning. Items are given a 6-reponse option format (No Problem, Slight Problem, Moderate Problem, Marked Problem, Extreme Problem and Not Applicable). The subscale results are derived by summing the respective items for that subscale and transforming the scores into a range of 0 to 100, the higher the scores indicating a greater impact of the disease on the aspect measured. The PSP-QoL also comprises of a Life Satisfaction rating gauge, which is a visual analog scale with a range of 0 (worst) to 100 (best).
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies number of participants who had response on Week 52. 'Number Analyzed' signifies the number of participants who were evaluated for the specified parameter.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 142 264
Mean (Standard Error)
Unit of Measure: Score on a scale
Physical Scale Score Number Analyzed 142 participants 264 participants
11.3  (1.5) 11.2  (1.1)
Mental Scale Score Number Analyzed 140 participants 264 participants
5.6  (1.4) 6.1  (1.0)
Satisfaction With Your Life Today Number Analyzed 141 participants 264 participants
-3.7  (1.8) -5.4  (1.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Physical scale score: Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in PSP-QoL as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for PSP-QoL, baseline PSP-QoL by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9304
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-3.6 to 3.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Mental scale score: Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in PSPQoL as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-bytime interaction, baseline for PSP-QoL, baseline PSP-QoL by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7859
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-2.8 to 3.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Satisfaction With Your Life Today: Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in PSPQoL as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-bytime interaction, baseline for PSP-QoL, baseline PSP-QoL by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4297
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-5.8 to 2.5
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Schwab and England Activities of Daily Living (SEADL) Scale Score at Week 48
Hide Description The SEADL scale is a means of assessing a person's ability to perform daily activities in terms of speed and independence, with 100% indicating total independence, falling to 0%, which indicates a state of complete dependence. The individual is asked to rate his or her function using an 11-point scale (10% increments), from 100% (completely independent; able to do all chores without slowness, difficulty, or impairment; essentially normal; unaware of any difficulty) to 0% (vegetative functions such as swallowing, bladder and bowels are not functioning; bedridden). A negative change from baseline indicates worsening.
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies total number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 140 277
Mean (Standard Error)
Unit of Measure: Score on a scale
-13.7  (1.4) -11.7  (1.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in SEADL as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for SEADL , baseline SEADL by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2084
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-1.1 to 5.2
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 52
Hide Description The Clinical Global Impression of Severity (CGI-S) Rating evaluates the severity of individual symptoms and treatment response in participants with mental disorders. The CGI-S is a 7-point scale that that requires the clinician to rate the severity of the patient's illness at the time of assessment. A rating of 1 is considered normal, or with the least severe symptoms, a rating of 7 is extremely ill, or the worst symptoms.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies total number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 140 269
Mean (Standard Error)
Unit of Measure: Score on a scale
0.6  (0.1) 0.6  (0.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in CGI-S as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for CGI-S, baseline CGI-S by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5701
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-0.2 to 0.1
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Phonemic Fluency Test Score at Week 48
Hide Description Phonemic fluency is a sensitive test for assessing frontal lobe dysfunction. Participants are given a letter of the alphabet and asked to name as many words as they can that start with that letter in 1 minute. The score for each trial is auto-calculated as follows: Trial 1: Total number of correct responses for the first letter (range 0 to 40); Trial 2: Total number of correct responses for the second letter (range 0 to 40). The total score from the two trials will be used for analysis (range 0 to 80). More number of words correlates to better phonemic fluency. A negative change from baseline indicates worsening.
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies total number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 141 273
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-0.9  (0.4) 0.0  (0.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in Phonemic Fluency Test as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline Phonemic Fluency Test, baseline Phonemic Fluency Test by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0517
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
-0.0 to 1.8
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Letter-Number Sequencing Test at Week 48
Hide Description Letter number is a test of working memory which involves ordering a series of up to 8 letters and numbers in which the numbers are repeated back first in order starting with the lowest number, then followed by the letters in alphabetical order. LNS consists of 10 items and each item has 3 trials rated as Incorrect (0) or Correct (1). The LNS total raw score (range 0 to 30) is auto-calculated by summing the 10 individual item scores (range 0 to 3 for each item). Higher number of correct items correlated to better performance and a negative change from baseline indicates worsening.
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies total number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 139 271
Mean (Standard Error)
Unit of Measure: Score on a scale
-1.9  (0.4) -1.1  (0.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in Letter Number Sequence as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline Letter Number Sequence, baseline Letter Number Sequence by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0387
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
0.0 to 1.7
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in Color Trails at Week 48
Hide Description The Color Trails test is a language free version of the Trail Making Test and was developed to allow for broader cross cultural assessment. For Part 1 (color trails test 1), the respondent uses a pencil to rapidly connect circles numbered 1-25 in sequence. For Part 2 (color trails test 2), the respondent rapidly connects number circles in sequence, but alternates between pink and yellow background. The length of time to complete each trial is recorded, along with qualitative features of performance indicative of brain dysfunction, such as near-misses, prompts, number sequence errors, and color sequence errors. Less time indicates better performance. A positive change from baseline indicates worsening.
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies total number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 143 279
Mean (Standard Error)
Unit of Measure: Seconds
Color Trails Test 1 16.8  (3.6) 16.9  (2.7)
Color Trails Test 2 10.6  (2.4) 10.5  (1.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Color Trails Test 1: Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in Color trails Test 1 as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for Color Trails Test 1, baseline Color Trails Test 1 by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9815
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-8.1 to 8.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Color Trails Test 2: Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in Color Trails Test 2 as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for Color Trails Test 2, baseline Color Trails Test 2 by time interaction, and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9869
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-5.7 to 5.6
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in Montreal Cognitive Assessment (MoCA) Score at Week 48
Hide Description The MOCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive function, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Scores on the MOCA range from 0-30, with higher score being better performance. A negative change from baseline indicates worsening.
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies total number of participants analyzed in this outcome measure.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 136 264
Mean (Standard Error)
Unit of Measure: Score on a scale
-1.0  (0.3) -0.5  (0.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MoCA as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for MoCA, baseline MoCA by time interaction,baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1763
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-0.2 to 1.2
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Number of Participants With Treatment Emergent Antibodies (Anti-BIIB092) Positive Results in Serum
Hide Description [Not Specified]
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ADA population - subset of the safety population with at least one evaluable post-baseline evaluable ADA samples.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 160 323
Measure Type: Count of Participants
Unit of Measure: Participants
7
   4.4%
0
   0.0%
15.Secondary Outcome
Title Change From Baseline of Brain Volumes as Determined by MRI at Week 52
Hide Description A 3 dimension (3D) T1-weighted MRI was performed to estimate brain volumes (e.g., ventricles, whole brain, midbrain, pons, superior cerebellar peduncle, third ventricle, and frontal lobes).
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy MRI population is the subset of the ITT population who had a least one measurable brain volumetric measurement. 'Number of Participants Analyzed' signifies number of participants who had response on Week 52. 'Number Analyzed' signifies the number of participants who were evaluated for the specified parameter.
Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period)
Hide Arm/Group Description:
Participants assigned to BIIB092 matching placebo intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo.
Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 milligrams (mg) IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period.
Overall Number of Participants Analyzed 114 238
Mean (Standard Error)
Unit of Measure: Cubic centimeter (cm^3)
Ventricles Volume: Change at Week 52 Number Analyzed 103 participants 222 participants
3.823  (0.302) 3.802  (0.216)
Whole Brain Volume: Change at Week 52 Number Analyzed 101 participants 210 participants
-18.612  (1.296) -19.126  (0.950)
Midbrain Volume: Change at Week 52 Number Analyzed 108 participants 224 participants
-0.116  (0.008) -0.120  (0.006)
Pons Volume: Change at Week 52 Number Analyzed 100 participants 223 participants
-0.198  (0.017) -0.198  (0.012)
Cerebellar Peduncle Volume: Change at Week 52 Number Analyzed 101 participants 216 participants
-0.005  (0.002) -0.004  (0.002)
Third Ventricle Volume: Change at Week 52 Number Analyzed 114 participants 238 participants
0.140  (0.014) 0.146  (0.010)
Frontal Lobe Volume: Change at Week 52 Number Analyzed 89 participants 178 participants
1.184  (0.279) 1.143  (0.205)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Ventricles Volume: Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MRI region as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for MRI region, baseline MRI region by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9527
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.021
Confidence Interval (2-Sided) 95%
-0.726 to 0.684
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Whole Brain Volume: Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MRI region as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for MRI region, baseline MRI region by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7357
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.514
Confidence Interval (2-Sided) 95%
-3.506 to 2.478
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Midbrain Volume: Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MRI region as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for MRI region, baseline MRI region by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6439
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.004
Confidence Interval (2-Sided) 95%
-0.023 to 0.014
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Pons Volume: Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MRI region as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for MRI region, baseline MRI region by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9864
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.000
Confidence Interval (2-Sided) 95%
-0.039 to 0.040
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Cerebellar Peduncle Volume: Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MRI region as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for MRI region, baseline MRI region by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7529
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.001
Confidence Interval (2-Sided) 95%
-0.004 to 0.006
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Third Ventricle Volume: Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MRI region as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for MRI region, baseline MRI region by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6850
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.006
Confidence Interval (2-Sided) 95%
-0.025 to 0.038
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo (PC Period), BIIB092 2000 mg (PC Period)
Comments Frontal Lobe Volume: Adjusted mean for each treatment group, difference with Placebo, 95% confidence interval and p-value at each time point were based on an MMRM model, with change from baseline in MRI region as dependent variable and with fixed effects of treatment group, time (categorical), treatment group-by-time interaction, baseline for MRI region, baseline MRI region by time interaction, baseline Color Trails 2 test (<=170 or >170 seconds) and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9000
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.041
Confidence Interval (2-Sided) 95%
-0.680 to 0.598
Estimation Comments [Not Specified]
Time Frame up to 140 weeks
Adverse Event Reporting Description Safety population: randomized participants who had received at least 1 dose of BIIB092 or Placebo. Participants randomized to Placebo that received at least 1 dose of BIIB092 2000 mg during the PC period will be counted in the BIIB092 2000 mg group for the safety population. Total number of participants exposed are participants who received drug in respective study periods. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.
 
Arm/Group Title Placebo (Placebo Controlled Period) BIIB092 2000 mg (Placebo Controlled Period) BIIB092 Late Start (Open-label Extension Period) BIIB092 Early Start (Open-label Extension Period)
Hide Arm/Group Description Participants assigned to BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period and receive only placebo. Participants who received at least one dose of BIIB092 2000 mg and were either assigned to BIIB092 2000 mg IV infusion or BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind PC period. Late start participants received only placebo in the placebo-controlled period and assigned to BIIB092 2000 mg IV infusion once every 4 weeks starting at Week 52 in the OLE period. Early start participants are those who received BIIB092 2000 mg in the placebo-controlled period and assigned to BIIB092 2000 mg IV infusion once every 4 weeks starting at Week 52 in the OLE period.
All-Cause Mortality
Placebo (Placebo Controlled Period) BIIB092 2000 mg (Placebo Controlled Period) BIIB092 Late Start (Open-label Extension Period) BIIB092 Early Start (Open-label Extension Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/162 (4.94%)   16/324 (4.94%)   10/137 (7.30%)   16/279 (5.73%) 
Hide Serious Adverse Events
Placebo (Placebo Controlled Period) BIIB092 2000 mg (Placebo Controlled Period) BIIB092 Late Start (Open-label Extension Period) BIIB092 Early Start (Open-label Extension Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   52/162 (32.10%)   88/324 (27.16%)   40/137 (29.20%)   63/279 (22.58%) 
Blood and lymphatic system disorders         
Anaemia  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Iron deficiency anaemia  1  1/162 (0.62%)  1/324 (0.31%)  1/137 (0.73%)  0/279 (0.00%) 
Cardiac disorders         
Acute myocardial infarction  1  0/162 (0.00%)  0/324 (0.00%)  2/137 (1.46%)  0/279 (0.00%) 
Atrial fibrillation  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Atrioventricular block complete  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Atrioventricular block second degree  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Cardiac arrest  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Cardiac failure  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Cardio-respiratory arrest  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Hypertensive heart disease  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Myocardial ischaemia  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Gastrointestinal disorders         
Colitis microscopic  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Constipation  1  1/162 (0.62%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Diarrhoea  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Dysphagia  1  5/162 (3.09%)  3/324 (0.93%)  1/137 (0.73%)  4/279 (1.43%) 
Faecaloma  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Femoral hernia  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Gastritis  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Hernial eventration  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Hiatus hernia  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Large intestine polyp  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Melaena  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Umbilical hernia  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Upper gastrointestinal haemorrhage  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Volvulus  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Vomiting  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
General disorders         
Cyst  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Death  1  0/162 (0.00%)  2/324 (0.62%)  1/137 (0.73%)  2/279 (0.72%) 
Drowning  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Euthanasia  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Gait disturbance  1  0/162 (0.00%)  2/324 (0.62%)  0/137 (0.00%)  0/279 (0.00%) 
Gait inability  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
General physical health deterioration  1  1/162 (0.62%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Multiple organ dysfunction syndrome  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  1/279 (0.36%) 
Systemic inflammatory response syndrome  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Hepatobiliary disorders         
Cholelithiasis  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Infections and infestations         
Abscess neck  1  1/162 (0.62%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Bacteraemia  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  2/279 (0.72%) 
Bacterial infection  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Bronchitis  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  2/279 (0.72%) 
Clostridium difficile colitis  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Cystitis  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Diverticulitis  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Escherichia urinary tract infection  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Gastroenteritis  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Infection  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Influenza  1  1/162 (0.62%)  1/324 (0.31%)  0/137 (0.00%)  1/279 (0.36%) 
Parainfluenzae virus infection  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Pneumonia  1  0/162 (0.00%)  10/324 (3.09%)  5/137 (3.65%)  6/279 (2.15%) 
Pneumonia influenzal  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Pulmonary sepsis  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Pulmonary tuberculosis  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Respiratory syncytial virus bronchitis  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Respiratory tract infection  1  0/162 (0.00%)  2/324 (0.62%)  0/137 (0.00%)  0/279 (0.00%) 
Sepsis  1  0/162 (0.00%)  2/324 (0.62%)  1/137 (0.73%)  2/279 (0.72%) 
Septic shock  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Subcutaneous abscess  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Urinary tract infection  1  3/162 (1.85%)  1/324 (0.31%)  2/137 (1.46%)  4/279 (1.43%) 
Urosepsis  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Viral infection  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Wound infection staphylococcal  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Injury, poisoning and procedural complications         
Ankle fracture  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Cervical vertebral fracture  1  0/162 (0.00%)  3/324 (0.93%)  0/137 (0.00%)  2/279 (0.72%) 
Clavicle fracture  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Concussion  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Contusion  1  1/162 (0.62%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Craniocerebral injury  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Facial bones fracture  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Fall  1  10/162 (6.17%)  41/324 (12.65%)  8/137 (5.84%)  11/279 (3.94%) 
Femoral neck fracture  1  1/162 (0.62%)  3/324 (0.93%)  0/137 (0.00%)  0/279 (0.00%) 
Femur fracture  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  2/279 (0.72%) 
Fracture  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Hip fracture  1  0/162 (0.00%)  2/324 (0.62%)  1/137 (0.73%)  0/279 (0.00%) 
Human bite  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Humerus fracture  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  1/279 (0.36%) 
Joint dislocation  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Lumbar vertebral fracture  1  1/162 (0.62%)  0/324 (0.00%)  1/137 (0.73%)  1/279 (0.36%) 
Musculoskeletal foreign body  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Open globe injury  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  1/279 (0.36%) 
Periprosthetic fracture  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Post procedural haemorrhage  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Radius fracture  1  0/162 (0.00%)  3/324 (0.93%)  0/137 (0.00%)  0/279 (0.00%) 
Rib fracture  1  1/162 (0.62%)  4/324 (1.23%)  2/137 (1.46%)  0/279 (0.00%) 
Road traffic accident  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Scapula fracture  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Skin laceration  1  1/162 (0.62%)  4/324 (1.23%)  0/137 (0.00%)  1/279 (0.36%) 
Spinal compression fracture  1  0/162 (0.00%)  1/324 (0.31%)  1/137 (0.73%)  2/279 (0.72%) 
Spinal fracture  1  0/162 (0.00%)  1/324 (0.31%)  1/137 (0.73%)  0/279 (0.00%) 
Subdural haematoma  1  1/162 (0.62%)  2/324 (0.62%)  1/137 (0.73%)  0/279 (0.00%) 
Tendon injury  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Tendon rupture  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Thermal burn  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Thoracic vertebral fracture  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Tibia fracture  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Traumatic haematoma  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Traumatic intracranial haemorrhage  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Wrist fracture  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Wrong dose  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Investigations         
Blood creatine phosphokinase increased  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Haemoglobin decreased  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Liver function test increased  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Lumbar puncture  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Metabolism and nutrition disorders         
Dehydration  1  0/162 (0.00%)  1/324 (0.31%)  1/137 (0.73%)  1/279 (0.36%) 
Diabetes mellitus inadequate control  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Failure to thrive  1  0/162 (0.00%)  2/324 (0.62%)  0/137 (0.00%)  0/279 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/162 (0.00%)  2/324 (0.62%)  0/137 (0.00%)  0/279 (0.00%) 
Chondrocalcinosis  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Haematoma muscle  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Muscle rigidity  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Osteitis  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Osteoarthritis  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Pain in extremity  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Breast cancer  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Breast neoplasm  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Colorectal cancer  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Lung adenocarcinoma  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Malignant melanoma  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Malignant melanoma in situ  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Metastatic gastric cancer  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Pancreatic carcinoma  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  1/279 (0.36%) 
Pituitary tumour benign  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Prostate cancer  1  0/162 (0.00%)  1/324 (0.31%)  1/137 (0.73%)  0/279 (0.00%) 
Nervous system disorders         
Akathisia  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Cerebral disorder  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Cerebrovascular accident  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  2/279 (0.72%) 
Dyskinesia  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Encephalopathy  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Epilepsy  1  0/162 (0.00%)  2/324 (0.62%)  0/137 (0.00%)  0/279 (0.00%) 
Lumbosacral radiculopathy  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Metabolic encephalopathy  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Monoparesis  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Movement disorder  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Neurological decompensation  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Noninfective encephalitis  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Peroneal nerve palsy  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Progressive supranuclear palsy  1  3/162 (1.85%)  6/324 (1.85%)  5/137 (3.65%)  4/279 (1.43%) 
Seizure  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  2/279 (0.72%) 
Somnolence  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Status epilepticus  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Subarachnoid haemorrhage  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Syncope  1  1/162 (0.62%)  2/324 (0.62%)  1/137 (0.73%)  2/279 (0.72%) 
Transient ischaemic attack  1  1/162 (0.62%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Psychiatric disorders         
Agitation  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Anxiety  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Assisted suicide  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Confusional state  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Hallucination  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Insomnia  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Mental status changes  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  1/279 (0.36%) 
Suicidal ideation  1  0/162 (0.00%)  2/324 (0.62%)  2/137 (1.46%)  1/279 (0.36%) 
Suicide attempt  1  0/162 (0.00%)  2/324 (0.62%)  1/137 (0.73%)  0/279 (0.00%) 
Renal and urinary disorders         
Acute kidney injury  1  0/162 (0.00%)  2/324 (0.62%)  0/137 (0.00%)  1/279 (0.36%) 
Calculus urinary  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Hydronephrosis  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Nephrolithiasis  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Renal impairment  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Ureterolithiasis  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Urge incontinence  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Urinary retention  1  1/162 (0.62%)  1/324 (0.31%)  0/137 (0.00%)  1/279 (0.36%) 
Reproductive system and breast disorders         
Acquired phimosis  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Benign prostatic hyperplasia  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Prostatitis  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  1/279 (0.36%) 
Respiratory, thoracic and mediastinal disorders         
Acute respiratory failure  1  0/162 (0.00%)  2/324 (0.62%)  1/137 (0.73%)  4/279 (1.43%) 
Aspiration  1  3/162 (1.85%)  0/324 (0.00%)  1/137 (0.73%)  1/279 (0.36%) 
Choking  1  1/162 (0.62%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Chronic obstructive pulmonary disease  1  2/162 (1.23%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Dyspnoea  1  0/162 (0.00%)  2/324 (0.62%)  0/137 (0.00%)  0/279 (0.00%) 
Pleural effusion  1  0/162 (0.00%)  0/324 (0.00%)  1/137 (0.73%)  0/279 (0.00%) 
Pneumonia aspiration  1  8/162 (4.94%)  6/324 (1.85%)  5/137 (3.65%)  12/279 (4.30%) 
Pneumothorax  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Pulmonary embolism  1  0/162 (0.00%)  2/324 (0.62%)  0/137 (0.00%)  1/279 (0.36%) 
Pulmonary oedema  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Respiratory arrest  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Respiratory depression  1  0/162 (0.00%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Respiratory distress  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Respiratory failure  1  3/162 (1.85%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Skin and subcutaneous tissue disorders         
Dermal cyst  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  0/279 (0.00%) 
Vascular disorders         
Aortic aneurysm  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
Deep vein thrombosis  1  0/162 (0.00%)  2/324 (0.62%)  0/137 (0.00%)  1/279 (0.36%) 
Haematoma  1  1/162 (0.62%)  0/324 (0.00%)  0/137 (0.00%)  1/279 (0.36%) 
Orthostatic hypotension  1  0/162 (0.00%)  1/324 (0.31%)  0/137 (0.00%)  0/279 (0.00%) 
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo (Placebo Controlled Period) BIIB092 2000 mg (Placebo Controlled Period) BIIB092 Late Start (Open-label Extension Period) BIIB092 Early Start (Open-label Extension Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   127/162 (78.40%)   235/324 (72.53%)   69/137 (50.36%)   130/279 (46.59%) 
Gastrointestinal disorders         
Constipation  1  15/162 (9.26%)  36/324 (11.11%)  4/137 (2.92%)  16/279 (5.73%) 
Diarrhoea  1  9/162 (5.56%)  23/324 (7.10%)  4/137 (2.92%)  9/279 (3.23%) 
Infections and infestations         
Nasopharyngitis  1  14/162 (8.64%)  28/324 (8.64%)  6/137 (4.38%)  16/279 (5.73%) 
Urinary tract infection  1  31/162 (19.14%)  56/324 (17.28%)  15/137 (10.95%)  36/279 (12.90%) 
Injury, poisoning and procedural complications         
Contusion  1  24/162 (14.81%)  41/324 (12.65%)  15/137 (10.95%)  24/279 (8.60%) 
Fall  1  83/162 (51.23%)  174/324 (53.70%)  45/137 (32.85%)  79/279 (28.32%) 
Head injury  1  8/162 (4.94%)  21/324 (6.48%)  4/137 (2.92%)  8/279 (2.87%) 
Skin abrasion  1  10/162 (6.17%)  28/324 (8.64%)  7/137 (5.11%)  12/279 (4.30%) 
Skin laceration  1  18/162 (11.11%)  40/324 (12.35%)  8/137 (5.84%)  14/279 (5.02%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  7/162 (4.32%)  18/324 (5.56%)  0/137 (0.00%)  3/279 (1.08%) 
Back pain  1  9/162 (5.56%)  15/324 (4.63%)  3/137 (2.19%)  11/279 (3.94%) 
Musculoskeletal pain  1  6/162 (3.70%)  19/324 (5.86%)  2/137 (1.46%)  3/279 (1.08%) 
Pain in extremity  1  7/162 (4.32%)  17/324 (5.25%)  0/137 (0.00%)  5/279 (1.79%) 
Nervous system disorders         
Dizziness  1  13/162 (8.02%)  18/324 (5.56%)  0/137 (0.00%)  3/279 (1.08%) 
Headache  1  22/162 (13.58%)  31/324 (9.57%)  3/137 (2.19%)  13/279 (4.66%) 
Psychiatric disorders         
Insomnia  1  14/162 (8.64%)  16/324 (4.94%)  4/137 (2.92%)  10/279 (3.58%) 
Vascular disorders         
Haematoma  1  11/162 (6.79%)  24/324 (7.41%)  7/137 (5.11%)  11/279 (3.94%) 
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Study got terminated as the primary endpoint was not met. PC period was completed at the time of termination. The study was not terminated due to a safety concern.
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 noncommercial 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: Biogen Study Medical Director
Organization: Biogen
Phone: 866-633-4636
EMail: clinicaltrials@biogen.com
Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT03068468    
Other Study ID Numbers: 251PP301
2016-002554-21 ( EudraCT Number )
CN002-012 ( Other Identifier: Briston-Myers Squibb )
First Submitted: February 27, 2017
First Posted: March 1, 2017
Results First Submitted: September 3, 2020
Results First Posted: December 21, 2020
Last Update Posted: December 21, 2020