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PASSPORT: Study of BIIB092 in Participants With Progressive Supranuclear Palsy

Sponsor
Biogen (Industry)
Overall Status
Terminated
CT.gov ID
NCT03068468
Collaborator
(none)
490
Enrollment
86
Locations
2
Arms
32.2
Actual Duration (Months)
5.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The Primary objective of the study is to evaluate the efficacy of BIIB092, compared to placebo, as measured by a change from baseline in the PSP Rating Scale (PSPRS) at Week 52 and to assess the safety and tolerability of BIIB092, relative to placebo, by measuring the frequency of deaths, SAEs, AEs leading to discontinuation, and Grade 3 & 4 laboratory abnormalities.

The Secondary objective of the study is to evaluate the efficacy of BIIB092, compared to placebo, as measured by a change in baseline in the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II at Week 52, to evaluate the efficacy of BIIB092, compared to placebo, as measured by the Clinical Global Impression of Change (CGI-C) at Week 52, to evaluate the efficacy of BIIB092, compared to placebo, as measured by a change in baseline in the Repeatable Battery for the Assessment of Neuropsychological Disease Severity (RBANS) at Week 52 and to assess the impact of BIIB092 on quality of life, relative to placebo, as measured by change from baseline on the Progressive Supranuclear Palsy Quality of Life scale (PSP-QoL) at Week 52.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This study, previously posted by Bristol-Myers Squibb, has transitioned to Biogen under a licensing agreement.

Study Design

Study Type:
Interventional
Actual Enrollment :
490 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Intravenously Administered BIIB092 in Participants With Progressive Supranuclear Palsy
Actual Study Start Date :
Jun 1, 2017
Actual Primary Completion Date :
Sep 6, 2019
Actual Study Completion Date :
Feb 7, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: BIIB092

Participants will receive BIIB092 50 mg/ml intravenous (IV) infusion once every 4 weeks for 48 weeks in double blind treatment period followed by BIIB092 50 mg/ml IV infusion once every 4 weeks starting at Week 52 up to Week 208.

Drug: BIIB092
BIIB092 intravenous infusion on specified days
Other Names:
  • BMS-986168

    		•
    Placebo Comparator: Placebo

    Participants will receive BIIB092 matching placebo IV infusion once every 4 weeks for 48 weeks in double blind treatment period followed by BIIB092 50 mg/ml IV infusion once every 4 weeks starting at Week 52 up to Week 208.

    Drug: Placebo
    Placebo intravenous infusion on specified days

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at Week 52 [Baseline, Week 52]

      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.

    2. Percentage of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and Adverse Events (AEs) Leading to Discontinuation of Drug [up to 52 weeks]

      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.

    Secondary Outcome Measures

    1. 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 [Baseline, Week 52]

      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.

    2. Clinical Global Impression of Change (CGI-C) Scale Score [Week 52]

      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.

    3. Change From Baseline in Progressive Supranuclear Palsy (PSP)-Cognitive Composite Battery Z-Score at Week 52 [Baseline, Week 52]

      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.

    4. Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Disease Severity (RBANS) Scale at Week 52 [Baseline, Week 52]

      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.

    5. Change From Baseline in Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) Score [Baseline, Week 52]

      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).

    6. Change From Baseline in Schwab and England Activities of Daily Living (SEADL) Scale Score at Week 48 [Baseline, Week 48]

      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.

    7. Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 52 [Baseline, Week 52]

      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.

    8. Change From Baseline in Phonemic Fluency Test Score at Week 48 [Baseline, Week 48]

      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.

    9. Change From Baseline in Letter-Number Sequencing Test at Week 48 [Baseline, Week 48]

      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.

    10. Change From Baseline in Color Trails at Week 48 [Baseline, Week 48]

      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.

    11. Change From Baseline in Montreal Cognitive Assessment (MoCA) Score at Week 48 [Baseline, Week 48]

      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.

    12. Number of Participants With Treatment Emergent Antibodies (Anti-BIIB092) Positive Results in Serum [Up to Week 48]

    13. Change From Baseline of Brain Volumes as Determined by MRI at Week 52 [Baseline, Week 52]

      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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    41 Years to 86 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Participants with probable or possible PSP

    • Able to ambulate independently or with assistance

    • Able to tolerate MRI

    • Have reliable caregiver to accompany participant to all study visits

    • Score greater or equal to 20 on the Mini Mental State Exam (MMSE) at screening

    • Participant must reside outside a skilled nursing facility or dementia care facility at the time of screening and admission to such a facility must not be planned

    Key Exclusion Criteria:

    • Presence of other significant neurological or psychiatric disorders

    • Diagnosis of amyotrophic lateral sclerosis (ALS) or other motor neuron disease

    • History of early, prominent rapid eye movement (REM) sleep behavior disorder

    • History of or screening brain MRI scan indicative of significant abnormality

    • Known history of serum or plasma progranulin level less than one standard deviation below the normal patient mean for the laboratory performing the assay

    NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Phoenix Arizona United States 85013
    2 Research Site Scottsdale Arizona United States 85259
    3 Research Site Sun City Arizona United States 85351
    4 Research Site Fountain Valley California United States 92708
    5 Research Site La Jolla California United States 92037
    6 Research Site Los Angeles California United States 90095
    7 Research Site San Francisco California United States 94158
    8 Research Site Boca Raton Florida United States 33486
    9 Research Site Gainesville Florida United States 32607
    10 Research Site Tampa Florida United States 33612-4742
    11 Research Site Chicago Illinois United States 60611
    12 Research Name Chicago Illinois United States 60612-3841
    13 Research Site Chicago Illinois United States 60637-1447
    14 Research Site Indianapolis Indiana United States 46202-2280
    15 Research Site Kansas City Kansas United States 66160
    16 Research Site New Orleans Louisiana United States 70121-2429
    17 Research Site Baltimore Maryland United States 21201
    18 Research Site Baltimore Maryland United States 21287
    19 Research Site Boston Massachusetts United States 02114
    20 Research Site Burlington Massachusetts United States 01702
    21 Research Site Farmington Hills Michigan United States 48334
    22 Research Site Minneapolis Minnesota United States 55455-0341
    23 Research Site New Brunswick New Jersey United States 08901
    24 Research Site Albany New York United States 12208
    25 Research Site New York New York United States 100029
    26 Research Site New York New York United States 10029
    27 Research Site New York New York United States 10032-3725
    28 Research Site Hershey Pennsylvania United States 17033
    29 Research Site Philadelphia Pennsylvania United States 19104
    30 Research Site Charleston South Carolina United States 29425
    31 Research Site Dallas Texas United States 75390-8869
    32 Research Site Charlottesville Virginia United States 22908-0394
    33 Research Site Seattle Washington United States 98122
    34 Research Site North Melbourne Victoria Australia
    35 Research Site Innsbruck Tirol Austria
    36 Research Site Vienna Austria
    37 Research Site London Ontario Canada
    38 Research Site Ottawa Ontario Canada
    39 Research Site Toronto Ontario Canada
    40 Research Site Bordeaux France
    41 Research Site Lille France
    42 Research Site Marseille France
    43 Research Site Nimes France
    44 Research Site Paris France
    45 Research Site Rennes France
    46 Research Site Toulouse France
    47 Research Site Munich Bavaria Germany
    48 Research Site Marburg Hessen Germany
    49 Research Site Rostock Mecklenburg-Western-Pommerania Germany
    50 Research Site Dusseldorf North Rhine-Westphalia Germany
    51 Research Site Dresden Sachsen Germany
    52 Research Site Kiel Schleswig-Holstein Germany
    53 Research Site Luebeck Schleswig-Holstein Germany
    54 Research Site Beelitz-Heilstatten Germany
    55 Research Site Bochum Germany
    56 Research Site Bonn Germany
    57 Research Site Essen Germany
    58 Research Site Kassel Germany
    59 Research Site Ulm Germany
    60 Research Site Athens Marousi Greece
    61 Research Site Salerno Campania Italy
    62 Research Site Pisa Italy
    63 Research Site Venice Lido Italy
    64 Research Site Nagoya Aichi Japan
    65 Research Site Kamagaya Chiba Japan
    66 Research Site Sapporo Hokkaido Japan
    67 Research Site Sagamihara Kanagawa Japan
    68 Research Site Kodaira Tokyo Japan
    69 Research Site Yonago Tottori Japan
    70 Research Site Shizuoka Japan
    71 Research Site Seoul Korea, Republic of
    72 Research Site Krasnoyarsk Russian Federation
    73 Research Site Moscow Russian Federation
    74 Research Site Pamplona Navarra Spain
    75 Research Site Barakaldo Vizcaya Spain
    76 Research Site Barcelona Spain
    77 Research Site Madrid Spain
    78 Research Site Sevilla Spain
    79 Research Site Valencia Spain
    80 Research Site Cambridge Cambridgeshire United Kingdom
    81 Research Site Brighton East Sussex United Kingdom
    82 Research Site Southampton Hampshire United Kingdom
    83 Research Site Liverpool Merseyside United Kingdom
    84 Research Site Newcastle Upon Tyne Tyne And Wear United Kingdom
    85 Research Site Newport Wales United Kingdom
    86 Research Site London United Kingdom

    Sponsors and Collaborators

    • Biogen

    Investigators

    • Study Director: Medical Director, Biogen

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Biogen
    ClinicalTrials.gov Identifier:
    NCT03068468
    Other Study ID Numbers:
    • 251PP301
    • 2016-002554-21
    • CN002-012
    First Posted:
    Mar 1, 2017
    Last Update Posted:
    Dec 21, 2020
    Last Verified:
    Nov 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Supranuclear Palsy, Progressive

    Study Results

    Participant Flow

    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 Detail 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)
    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 144 279 0 0
    NOT COMPLETED 22 45 0 0
    Period Title: Placebo-Controlled Period
    STARTED 0 0 140 276
    COMPLETED 0 0 0 0
    NOT COMPLETED 0 0 140 276

    Baseline Characteristics

    Arm/Group Title Placebo (PC Period) BIIB092 2000 mg (PC Period) Total
    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 Participants 165 321 486
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    68.9
    (6.57)
    68.7
    (7.02)
    68.7
    (6.86)
    Sex: Female, Male (Count of Participants)
    Female
    74
    44.8%
    136
    42.4%
    210
    43.2%
    Male
    91
    55.2%
    185
    57.6%
    276
    56.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    5
    3%
    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 (Count of 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%
    1
    0.3%
    1
    0.2%
    Japanese
    16
    9.7%
    23
    7.2%
    39
    8%
    Asian Other
    4
    2.4%
    10
    3.1%
    14
    2.9%
    Unknown
    3
    1.8%
    2
    0.6%
    5
    1%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at Week 52
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 139 278
    PSPRS: 28 items
    10.6
    (0.8)
    10.4
    (0.6)
    PSPRS: 15 items
    7.57
    (0.52)
    7.29
    (0.38)
    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
    Statistical Test of Hypothesis p-Value 0.8483
    Comments
    Method Mixed model for repeated measures (MMRM)
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -2.0 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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
    Statistical Test of Hypothesis p-Value 0.6503
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.28
    Confidence Interval (2-Sided) 95%
    -1.50 to 0.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 162 324
    Death
    4.9
    3%
    4.9
    1.5%
    SAEs
    32.1
    19.5%
    27.2
    8.5%
    AEs
    93.2
    56.5%
    92.9
    28.9%
    AEs Leading to Discontinuation of Drug
    11.1
    6.7%
    7.4
    2.3%
    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
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 143 270
    Mean (Standard Error) [Score on a scale]
    6.7
    (0.6)
    7.0
    (0.4)
    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
    Statistical Test of Hypothesis p-Value 0.6031
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    -1.0 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Clinical Global Impression of Change (CGI-C) Scale Score
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 138 271
    Mean (Standard Error) [Score on a scale]
    5.3
    (0.1)
    5.2
    (0.1)
    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
    Statistical Test of Hypothesis p-Value 0.7743
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Change From Baseline in Progressive Supranuclear Palsy (PSP)-Cognitive Composite Battery Z-Score at Week 52
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 134 249
    Mean (Standard Error) [z-score]
    -0.283
    (0.032)
    -0.245
    (0.024)
    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
    Statistical Test of Hypothesis p-Value 0.3180
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.038
    Confidence Interval (2-Sided) 95%
    -0.036 to 0.112
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Disease Severity (RBANS) Scale at Week 52
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 111 222
    Mean (Standard Error) [Score on a scale]
    -3.1
    (0.7)
    -3.2
    (0.5)
    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
    Statistical Test of Hypothesis p-Value 0.8270
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -1.8 to 1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Change From Baseline in Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) Score
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 142 264
    Physical Scale Score
    11.3
    (1.5)
    11.2
    (1.1)
    Mental Scale Score
    5.6
    (1.4)
    6.1
    (1.0)
    Satisfaction With Your Life Today
    -3.7
    (1.8)
    -5.4
    (1.3)
    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
    Statistical Test of Hypothesis p-Value 0.9304
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -3.6 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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
    Statistical Test of Hypothesis p-Value 0.7859
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.5
    Confidence Interval (2-Sided) 95%
    -2.8 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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
    Statistical Test of Hypothesis p-Value 0.4297
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.7
    Confidence Interval (2-Sided) 95%
    -5.8 to 2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Change From Baseline in Schwab and England Activities of Daily Living (SEADL) Scale Score at Week 48
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 140 277
    Mean (Standard Error) [Score on a scale]
    -13.7
    (1.4)
    -11.7
    (1.0)
    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
    Statistical Test of Hypothesis p-Value 0.2084
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value 2.0
    Confidence Interval (2-Sided) 95%
    -1.1 to 5.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 52
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 140 269
    Mean (Standard Error) [Score on a scale]
    0.6
    (0.1)
    0.6
    (0.0)
    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
    Statistical Test of Hypothesis p-Value 0.5701
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Change From Baseline in Phonemic Fluency Test Score at Week 48
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 141 273
    Mean (Standard Deviation) [Score on a scale]
    -0.9
    (0.4)
    0.0
    (0.3)
    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
    Statistical Test of Hypothesis p-Value 0.0517
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    -0.0 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Change From Baseline in Letter-Number Sequencing Test at Week 48
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 139 271
    Mean (Standard Error) [Score on a scale]
    -1.9
    (0.4)
    -1.1
    (0.3)
    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
    Statistical Test of Hypothesis p-Value 0.0387
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    0.0 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title Change From Baseline in Color Trails at Week 48
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 143 279
    Color Trails Test 1
    16.8
    (3.6)
    16.9
    (2.7)
    Color Trails Test 2
    10.6
    (2.4)
    10.5
    (1.8)
    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
    Statistical Test of Hypothesis p-Value 0.9815
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -8.1 to 8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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
    Statistical Test of Hypothesis p-Value 0.9869
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -5.7 to 5.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Secondary Outcome
    Title Change From Baseline in Montreal Cognitive Assessment (MoCA) Score at Week 48
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 136 264
    Mean (Standard Error) [Score on a scale]
    -1.0
    (0.3)
    -0.5
    (0.2)
    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
    Statistical Test of Hypothesis p-Value 0.1763
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.5
    Confidence Interval (2-Sided) 95%
    -0.2 to 1.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title Number of Participants With Treatment Emergent Antibodies (Anti-BIIB092) Positive Results in Serum
    Description
    Time Frame Up to Week 48

    Outcome Measure Data

    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)
    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.
    Measure Participants 160 323
    Count of Participants [Participants]
    7
    4.2%
    0
    0%
    15. Secondary Outcome
    Title Change From Baseline of Brain Volumes as Determined by MRI at Week 52
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 114 238
    Ventricles Volume: Change at Week 52
    3.823
    (0.302)
    3.802
    (0.216)
    Whole Brain Volume: Change at Week 52
    -18.612
    (1.296)
    -19.126
    (0.950)
    Midbrain Volume: Change at Week 52
    -0.116
    (0.008)
    -0.120
    (0.006)
    Pons Volume: Change at Week 52
    -0.198
    (0.017)
    -0.198
    (0.012)
    Cerebellar Peduncle Volume: Change at Week 52
    -0.005
    (0.002)
    -0.004
    (0.002)
    Third Ventricle Volume: Change at Week 52
    0.140
    (0.014)
    0.146
    (0.010)
    Frontal Lobe Volume: Change at Week 52
    1.184
    (0.279)
    1.143
    (0.205)
    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
    Statistical Test of Hypothesis p-Value 0.9527
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.021
    Confidence Interval (2-Sided) 95%
    -0.726 to 0.684
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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
    Statistical Test of Hypothesis p-Value 0.7357
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.514
    Confidence Interval (2-Sided) 95%
    -3.506 to 2.478
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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
    Statistical Test of Hypothesis p-Value 0.6439
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.004
    Confidence Interval (2-Sided) 95%
    -0.023 to 0.014
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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
    Statistical Test of Hypothesis p-Value 0.9864
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.000
    Confidence Interval (2-Sided) 95%
    -0.039 to 0.040
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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
    Statistical Test of Hypothesis p-Value 0.7529
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.001
    Confidence Interval (2-Sided) 95%
    -0.004 to 0.006
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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
    Statistical Test of Hypothesis p-Value 0.6850
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.006
    Confidence Interval (2-Sided) 95%
    -0.025 to 0.038
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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
    Statistical Test of Hypothesis p-Value 0.9000
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.041
    Confidence Interval (2-Sided) 95%
    -0.680 to 0.598
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    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)
    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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/162 (4.9%) 16/324 (4.9%) 10/137 (7.3%) 16/279 (5.7%)
    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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 52/162 (32.1%) 88/324 (27.2%) 40/137 (29.2%) 63/279 (22.6%)
    Blood and lymphatic system disorders
    Anaemia 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Iron deficiency anaemia 1/162 (0.6%) 1/324 (0.3%) 1/137 (0.7%) 0/279 (0%)
    Cardiac disorders
    Acute myocardial infarction 0/162 (0%) 0/324 (0%) 2/137 (1.5%) 0/279 (0%)
    Atrial fibrillation 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Atrioventricular block complete 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Atrioventricular block second degree 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Cardiac arrest 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Cardiac failure 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Cardio-respiratory arrest 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Hypertensive heart disease 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Myocardial ischaemia 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Gastrointestinal disorders
    Colitis microscopic 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Constipation 1/162 (0.6%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Diarrhoea 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Dysphagia 5/162 (3.1%) 3/324 (0.9%) 1/137 (0.7%) 4/279 (1.4%)
    Faecaloma 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Femoral hernia 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Gastritis 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Hernial eventration 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Hiatus hernia 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Large intestine polyp 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Melaena 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Umbilical hernia 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Upper gastrointestinal haemorrhage 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Volvulus 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Vomiting 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    General disorders
    Cyst 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Death 0/162 (0%) 2/324 (0.6%) 1/137 (0.7%) 2/279 (0.7%)
    Drowning 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Euthanasia 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Gait disturbance 0/162 (0%) 2/324 (0.6%) 0/137 (0%) 0/279 (0%)
    Gait inability 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    General physical health deterioration 1/162 (0.6%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Multiple organ dysfunction syndrome 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 1/279 (0.4%)
    Systemic inflammatory response syndrome 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Hepatobiliary disorders
    Cholelithiasis 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Infections and infestations
    Abscess neck 1/162 (0.6%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Bacteraemia 0/162 (0%) 0/324 (0%) 0/137 (0%) 2/279 (0.7%)
    Bacterial infection 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Bronchitis 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 2/279 (0.7%)
    Clostridium difficile colitis 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Cystitis 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Diverticulitis 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Escherichia urinary tract infection 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Gastroenteritis 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Infection 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Influenza 1/162 (0.6%) 1/324 (0.3%) 0/137 (0%) 1/279 (0.4%)
    Parainfluenzae virus infection 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Pneumonia 0/162 (0%) 10/324 (3.1%) 5/137 (3.6%) 6/279 (2.2%)
    Pneumonia influenzal 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Pulmonary sepsis 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Pulmonary tuberculosis 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Respiratory syncytial virus bronchitis 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Respiratory tract infection 0/162 (0%) 2/324 (0.6%) 0/137 (0%) 0/279 (0%)
    Sepsis 0/162 (0%) 2/324 (0.6%) 1/137 (0.7%) 2/279 (0.7%)
    Septic shock 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Subcutaneous abscess 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Urinary tract infection 3/162 (1.9%) 1/324 (0.3%) 2/137 (1.5%) 4/279 (1.4%)
    Urosepsis 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Viral infection 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Wound infection staphylococcal 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Injury, poisoning and procedural complications
    Ankle fracture 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Cervical vertebral fracture 0/162 (0%) 3/324 (0.9%) 0/137 (0%) 2/279 (0.7%)
    Clavicle fracture 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Concussion 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Contusion 1/162 (0.6%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Craniocerebral injury 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Facial bones fracture 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Fall 10/162 (6.2%) 41/324 (12.7%) 8/137 (5.8%) 11/279 (3.9%)
    Femoral neck fracture 1/162 (0.6%) 3/324 (0.9%) 0/137 (0%) 0/279 (0%)
    Femur fracture 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 2/279 (0.7%)
    Fracture 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Hip fracture 0/162 (0%) 2/324 (0.6%) 1/137 (0.7%) 0/279 (0%)
    Human bite 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Humerus fracture 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 1/279 (0.4%)
    Joint dislocation 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Lumbar vertebral fracture 1/162 (0.6%) 0/324 (0%) 1/137 (0.7%) 1/279 (0.4%)
    Musculoskeletal foreign body 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Open globe injury 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 1/279 (0.4%)
    Periprosthetic fracture 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Post procedural haemorrhage 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Radius fracture 0/162 (0%) 3/324 (0.9%) 0/137 (0%) 0/279 (0%)
    Rib fracture 1/162 (0.6%) 4/324 (1.2%) 2/137 (1.5%) 0/279 (0%)
    Road traffic accident 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Scapula fracture 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Skin laceration 1/162 (0.6%) 4/324 (1.2%) 0/137 (0%) 1/279 (0.4%)
    Spinal compression fracture 0/162 (0%) 1/324 (0.3%) 1/137 (0.7%) 2/279 (0.7%)
    Spinal fracture 0/162 (0%) 1/324 (0.3%) 1/137 (0.7%) 0/279 (0%)
    Subdural haematoma 1/162 (0.6%) 2/324 (0.6%) 1/137 (0.7%) 0/279 (0%)
    Tendon injury 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Tendon rupture 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Thermal burn 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Thoracic vertebral fracture 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Tibia fracture 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Traumatic haematoma 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Traumatic intracranial haemorrhage 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Wrist fracture 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Wrong dose 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Investigations
    Blood creatine phosphokinase increased 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Haemoglobin decreased 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Liver function test increased 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Lumbar puncture 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Metabolism and nutrition disorders
    Dehydration 0/162 (0%) 1/324 (0.3%) 1/137 (0.7%) 1/279 (0.4%)
    Diabetes mellitus inadequate control 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Failure to thrive 0/162 (0%) 2/324 (0.6%) 0/137 (0%) 0/279 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/162 (0%) 2/324 (0.6%) 0/137 (0%) 0/279 (0%)
    Chondrocalcinosis 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Haematoma muscle 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Muscle rigidity 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Osteitis 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Osteoarthritis 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Pain in extremity 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Breast neoplasm 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Colorectal cancer 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Lung adenocarcinoma 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Malignant melanoma 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Malignant melanoma in situ 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Metastatic gastric cancer 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Pancreatic carcinoma 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 1/279 (0.4%)
    Pituitary tumour benign 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Prostate cancer 0/162 (0%) 1/324 (0.3%) 1/137 (0.7%) 0/279 (0%)
    Nervous system disorders
    Akathisia 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Cerebral disorder 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Cerebrovascular accident 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 2/279 (0.7%)
    Dyskinesia 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Encephalopathy 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Epilepsy 0/162 (0%) 2/324 (0.6%) 0/137 (0%) 0/279 (0%)
    Lumbosacral radiculopathy 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Metabolic encephalopathy 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Monoparesis 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Movement disorder 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Neurological decompensation 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Noninfective encephalitis 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Peroneal nerve palsy 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Progressive supranuclear palsy 3/162 (1.9%) 6/324 (1.9%) 5/137 (3.6%) 4/279 (1.4%)
    Seizure 0/162 (0%) 0/324 (0%) 0/137 (0%) 2/279 (0.7%)
    Somnolence 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Status epilepticus 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Subarachnoid haemorrhage 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Syncope 1/162 (0.6%) 2/324 (0.6%) 1/137 (0.7%) 2/279 (0.7%)
    Transient ischaemic attack 1/162 (0.6%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Psychiatric disorders
    Agitation 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Anxiety 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Assisted suicide 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Confusional state 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Hallucination 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Insomnia 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Mental status changes 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 1/279 (0.4%)
    Suicidal ideation 0/162 (0%) 2/324 (0.6%) 2/137 (1.5%) 1/279 (0.4%)
    Suicide attempt 0/162 (0%) 2/324 (0.6%) 1/137 (0.7%) 0/279 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/162 (0%) 2/324 (0.6%) 0/137 (0%) 1/279 (0.4%)
    Calculus urinary 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Hydronephrosis 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Nephrolithiasis 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Renal impairment 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Ureterolithiasis 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Urge incontinence 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Urinary retention 1/162 (0.6%) 1/324 (0.3%) 0/137 (0%) 1/279 (0.4%)
    Reproductive system and breast disorders
    Acquired phimosis 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Benign prostatic hyperplasia 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Prostatitis 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 1/279 (0.4%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/162 (0%) 2/324 (0.6%) 1/137 (0.7%) 4/279 (1.4%)
    Aspiration 3/162 (1.9%) 0/324 (0%) 1/137 (0.7%) 1/279 (0.4%)
    Choking 1/162 (0.6%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Chronic obstructive pulmonary disease 2/162 (1.2%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Dyspnoea 0/162 (0%) 2/324 (0.6%) 0/137 (0%) 0/279 (0%)
    Pleural effusion 0/162 (0%) 0/324 (0%) 1/137 (0.7%) 0/279 (0%)
    Pneumonia aspiration 8/162 (4.9%) 6/324 (1.9%) 5/137 (3.6%) 12/279 (4.3%)
    Pneumothorax 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Pulmonary embolism 0/162 (0%) 2/324 (0.6%) 0/137 (0%) 1/279 (0.4%)
    Pulmonary oedema 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Respiratory arrest 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Respiratory depression 0/162 (0%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Respiratory distress 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Respiratory failure 3/162 (1.9%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Skin and subcutaneous tissue disorders
    Dermal cyst 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 0/279 (0%)
    Vascular disorders
    Aortic aneurysm 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Deep vein thrombosis 0/162 (0%) 2/324 (0.6%) 0/137 (0%) 1/279 (0.4%)
    Haematoma 1/162 (0.6%) 0/324 (0%) 0/137 (0%) 1/279 (0.4%)
    Orthostatic hypotension 0/162 (0%) 1/324 (0.3%) 0/137 (0%) 0/279 (0%)
    Other (Not Including 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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 127/162 (78.4%) 235/324 (72.5%) 69/137 (50.4%) 130/279 (46.6%)
    Gastrointestinal disorders
    Constipation 15/162 (9.3%) 36/324 (11.1%) 4/137 (2.9%) 16/279 (5.7%)
    Diarrhoea 9/162 (5.6%) 23/324 (7.1%) 4/137 (2.9%) 9/279 (3.2%)
    Infections and infestations
    Nasopharyngitis 14/162 (8.6%) 28/324 (8.6%) 6/137 (4.4%) 16/279 (5.7%)
    Urinary tract infection 31/162 (19.1%) 56/324 (17.3%) 15/137 (10.9%) 36/279 (12.9%)
    Injury, poisoning and procedural complications
    Contusion 24/162 (14.8%) 41/324 (12.7%) 15/137 (10.9%) 24/279 (8.6%)
    Fall 83/162 (51.2%) 174/324 (53.7%) 45/137 (32.8%) 79/279 (28.3%)
    Head injury 8/162 (4.9%) 21/324 (6.5%) 4/137 (2.9%) 8/279 (2.9%)
    Skin abrasion 10/162 (6.2%) 28/324 (8.6%) 7/137 (5.1%) 12/279 (4.3%)
    Skin laceration 18/162 (11.1%) 40/324 (12.3%) 8/137 (5.8%) 14/279 (5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 7/162 (4.3%) 18/324 (5.6%) 0/137 (0%) 3/279 (1.1%)
    Back pain 9/162 (5.6%) 15/324 (4.6%) 3/137 (2.2%) 11/279 (3.9%)
    Musculoskeletal pain 6/162 (3.7%) 19/324 (5.9%) 2/137 (1.5%) 3/279 (1.1%)
    Pain in extremity 7/162 (4.3%) 17/324 (5.2%) 0/137 (0%) 5/279 (1.8%)
    Nervous system disorders
    Dizziness 13/162 (8%) 18/324 (5.6%) 0/137 (0%) 3/279 (1.1%)
    Headache 22/162 (13.6%) 31/324 (9.6%) 3/137 (2.2%) 13/279 (4.7%)
    Psychiatric disorders
    Insomnia 14/162 (8.6%) 16/324 (4.9%) 4/137 (2.9%) 10/279 (3.6%)
    Vascular disorders
    Haematoma 11/162 (6.8%) 24/324 (7.4%) 7/137 (5.1%) 11/279 (3.9%)

    Limitations/Caveats

    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.

    More Information

    Certain Agreements

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

    Our agreement is subject to confidentiality but generally the PI can publish, for 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

    Name/Title Biogen Study Medical Director
    Organization Biogen
    Phone 866-633-4636
    Email clinicaltrials@biogen.com
    Responsible Party:
    Biogen
    ClinicalTrials.gov Identifier:
    NCT03068468
    Other Study ID Numbers:
    • 251PP301
    • 2016-002554-21
    • CN002-012
    First Posted:
    Mar 1, 2017
    Last Update Posted:
    Dec 21, 2020
    Last Verified:
    Nov 1, 2020