Supranuclear Palsy, Progressive
Conditions
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.
Detailed description
This study, previously posted by Bristol-Myers Squibb, has transitioned to Biogen under a licensing agreement.
Interventions
DRUGBIIB092
BIIB092 intravenous infusion on specified days
DRUGPlacebo
Placebo intravenous infusion on specified days
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
41 Years to 86 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Number of Participants With Treatment Emergent Antibodies (Anti-BIIB092) Positive Results in Serum | Up to Week 48 | — |
| 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). |
| 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. |
| 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. |
Countries
Australia, Austria, Canada, France, Germany, Greece, Italy, Japan, Russia, South Korea, Spain, United Kingdom, United States
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 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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (PC Period) 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. | 165 |
| BIIB092 2000 mg (PC Period) 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. | 321 |
| Total | 486 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Open-Label Extension Period | Adverse Event | 0 | 0 | 13 | 17 |
| Open-Label Extension Period | Death | 0 | 0 | 0 | 1 |
| Open-Label Extension Period | Failure to Meet Randomization Criteria | 0 | 0 | 2 | 0 |
| Open-Label Extension Period | Lack of Efficacy | 0 | 0 | 1 | 2 |
| Open-Label Extension Period | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Open-Label Extension Period | Reason not Specified | 0 | 0 | 1 | 4 |
| Open-Label Extension Period | Withdrawal by Parent/Guardian | 0 | 0 | 0 | 4 |
| Open-Label Extension Period | Withdrawal by Sponsor | 0 | 0 | 115 | 228 |
| Open-Label Extension Period | Withdrawal by Subject | 0 | 0 | 7 | 20 |
| Placebo-Controlled Period | Adverse Event | 16 | 21 | 0 | 0 |
| Placebo-Controlled Period | Death | 0 | 1 | 0 | 0 |
| Placebo-Controlled Period | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Placebo-Controlled Period | Randomized but not Treated | 1 | 3 | 0 | 0 |
| Placebo-Controlled Period | Reason Not Specified | 1 | 6 | 0 | 0 |
| Placebo-Controlled Period | Withdrawal by Parent/Guardian | 1 | 2 | 0 | 0 |
| Placebo-Controlled Period | Withdrawal by Subject | 3 | 11 | 0 | 0 |
Baseline characteristics
| Characteristic | BIIB092 2000 mg (PC Period) | Total | Placebo (PC Period) |
|---|---|---|---|
| Age, Continuous | 68.7 years STANDARD_DEVIATION 7.02 | 68.7 years STANDARD_DEVIATION 6.86 | 68.9 years STANDARD_DEVIATION 6.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 12 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 242 Participants | 359 Participants | 117 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 72 Participants | 115 Participants | 43 Participants |
| Race/Ethnicity, Customized Race Asian Indian | 3 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Asian Other | 10 Participants | 14 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Chinese | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Japanese | 23 Participants | 39 Participants | 16 Participants |
| Race/Ethnicity, Customized Race Unknown | 2 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Race White | 281 Participants | 419 Participants | 138 Participants |
| Sex: Female, Male Female | 136 Participants | 210 Participants | 74 Participants |
| Sex: Female, Male Male | 185 Participants | 276 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 162 | 16 / 324 | 10 / 137 | 16 / 279 |
| other Total, other adverse events | 127 / 162 | 235 / 324 | 69 / 137 | 130 / 279 |
| serious Total, serious adverse events | 52 / 162 | 88 / 324 | 40 / 137 | 63 / 279 |
Outcome results
Primary
Change From Baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at 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.
Time frame: Baseline, Week 52
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PC Period) | Change From Baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at Week 52 | PSPRS: 28 items | 10.6 Score on a scale | Standard Error 0.8 |
| Placebo (PC Period) | Change From Baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at Week 52 | PSPRS: 15 items | 7.57 Score on a scale | Standard Error 0.52 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at Week 52 | PSPRS: 28 items | 10.4 Score on a scale | Standard Error 0.6 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at Week 52 | PSPRS: 15 items | 7.29 Score on a scale | Standard Error 0.38 |
Comparison: 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.p-value: 0.848395% CI: [-2, 1.6]Mixed model for repeated measures (MMRM)
Comparison: 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.p-value: 0.650395% CI: [-1.5, 0.94]MMRM
Primary
Percentage of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and Adverse Events (AEs) Leading to Discontinuation of Drug
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (PC Period) | Percentage of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and Adverse Events (AEs) Leading to Discontinuation of Drug | AEs | 93.2 Percentage of participants |
| Placebo (PC Period) | Percentage of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and Adverse Events (AEs) Leading to Discontinuation of Drug | SAEs | 32.1 Percentage of participants |
| Placebo (PC Period) | Percentage of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and Adverse Events (AEs) Leading to Discontinuation of Drug | AEs Leading to Discontinuation of Drug | 11.1 Percentage of participants |
| Placebo (PC Period) | Percentage of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and Adverse Events (AEs) Leading to Discontinuation of Drug | Death | 4.9 Percentage of participants |
| BIIB092 2000 mg (PC Period) | Percentage of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and Adverse Events (AEs) Leading to Discontinuation of Drug | AEs Leading to Discontinuation of Drug | 7.4 Percentage of participants |
| BIIB092 2000 mg (PC Period) | Percentage of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and Adverse Events (AEs) Leading to Discontinuation of Drug | SAEs | 27.2 Percentage of participants |
| BIIB092 2000 mg (PC Period) | Percentage of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and Adverse Events (AEs) Leading to Discontinuation of Drug | AEs | 92.9 Percentage of participants |
| BIIB092 2000 mg (PC Period) | Percentage of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and Adverse Events (AEs) Leading to Discontinuation of Drug | Death | 4.9 Percentage of participants |
Secondary
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at 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.
Time frame: Baseline, Week 52
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PC Period) | Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 52 | 0.6 Score on a scale | Standard Error 0.1 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 52 | 0.6 Score on a scale | Standard Error 0 |
Comparison: 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.p-value: 0.570195% CI: [-0.2, 0.1]MMRM
Secondary
Change From Baseline in Color Trails at 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.
Time frame: Baseline, Week 48
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PC Period) | Change From Baseline in Color Trails at Week 48 | Color Trails Test 2 | 10.6 Seconds | Standard Error 2.4 |
| Placebo (PC Period) | Change From Baseline in Color Trails at Week 48 | Color Trails Test 1 | 16.8 Seconds | Standard Error 3.6 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Color Trails at Week 48 | Color Trails Test 2 | 10.5 Seconds | Standard Error 1.8 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Color Trails at Week 48 | Color Trails Test 1 | 16.9 Seconds | Standard Error 2.7 |
Comparison: 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.p-value: 0.981595% CI: [-8.1, 8.3]MMRM
Comparison: 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.p-value: 0.986995% CI: [-5.7, 5.6]MMRM
Secondary
Change From Baseline in Letter-Number Sequencing Test at 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.
Time frame: Baseline, Week 48
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PC Period) | Change From Baseline in Letter-Number Sequencing Test at Week 48 | -1.9 Score on a scale | Standard Error 0.4 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Letter-Number Sequencing Test at Week 48 | -1.1 Score on a scale | Standard Error 0.3 |
Comparison: 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.p-value: 0.038795% CI: [0, 1.7]MMRM
Secondary
Change From Baseline in Montreal Cognitive Assessment (MoCA) Score at 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.
Time frame: Baseline, Week 48
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PC Period) | Change From Baseline in Montreal Cognitive Assessment (MoCA) Score at Week 48 | -1.0 Score on a scale | Standard Error 0.3 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Montreal Cognitive Assessment (MoCA) Score at Week 48 | -0.5 Score on a scale | Standard Error 0.2 |
Comparison: 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.p-value: 0.176395% CI: [-0.2, 1.2]MMRM
Secondary
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
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PC Period) | 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 | 6.7 Score on a scale | Standard Error 0.6 |
| BIIB092 2000 mg (PC Period) | 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 | 7.0 Score on a scale | Standard Error 0.4 |
Comparison: 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.p-value: 0.603195% CI: [-1, 1.7]MMRM
Secondary
Change From Baseline in Phonemic Fluency Test Score at 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.
Time frame: Baseline, Week 48
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PC Period) | Change From Baseline in Phonemic Fluency Test Score at Week 48 | -0.9 Score on a scale | Standard Deviation 0.4 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Phonemic Fluency Test Score at Week 48 | 0.0 Score on a scale | Standard Deviation 0.3 |
Comparison: 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.p-value: 0.051795% CI: [0, 1.8]MMRM
Secondary
Change From Baseline in Progressive Supranuclear Palsy (PSP)-Cognitive Composite Battery Z-Score at 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.
Time frame: Baseline, Week 52
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PC Period) | Change From Baseline in Progressive Supranuclear Palsy (PSP)-Cognitive Composite Battery Z-Score at Week 52 | -0.283 z-score | Standard Error 0.032 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Progressive Supranuclear Palsy (PSP)-Cognitive Composite Battery Z-Score at Week 52 | -0.245 z-score | Standard Error 0.024 |
Comparison: 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.p-value: 0.31895% CI: [-0.036, 0.112]MMRM
Secondary
Change From Baseline in Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) Score
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PC Period) | Change From Baseline in Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) Score | Satisfaction With Your Life Today | -3.7 Score on a scale | Standard Error 1.8 |
| Placebo (PC Period) | Change From Baseline in Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) Score | Physical Scale Score | 11.3 Score on a scale | Standard Error 1.5 |
| Placebo (PC Period) | Change From Baseline in Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) Score | Mental Scale Score | 5.6 Score on a scale | Standard Error 1.4 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) Score | Physical Scale Score | 11.2 Score on a scale | Standard Error 1.1 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) Score | Mental Scale Score | 6.1 Score on a scale | Standard Error 1 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) Score | Satisfaction With Your Life Today | -5.4 Score on a scale | Standard Error 1.3 |
Comparison: 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.p-value: 0.930495% CI: [-3.6, 3.3]MMRM
Comparison: 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.p-value: 0.785995% CI: [-2.8, 3.7]MMRM
Comparison: 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.p-value: 0.429795% CI: [-5.8, 2.5]MMRM
Secondary
Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Disease Severity (RBANS) Scale at 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.
Time frame: Baseline, Week 52
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PC Period) | Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Disease Severity (RBANS) Scale at Week 52 | -3.1 Score on a scale | Standard Error 0.7 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Disease Severity (RBANS) Scale at Week 52 | -3.2 Score on a scale | Standard Error 0.5 |
Comparison: 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.p-value: 0.82795% CI: [-1.8, 1.4]MMRM
Secondary
Change From Baseline in Schwab and England Activities of Daily Living (SEADL) Scale Score at 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.
Time frame: Baseline, Week 48
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PC Period) | Change From Baseline in Schwab and England Activities of Daily Living (SEADL) Scale Score at Week 48 | -13.7 Score on a scale | Standard Error 1.4 |
| BIIB092 2000 mg (PC Period) | Change From Baseline in Schwab and England Activities of Daily Living (SEADL) Scale Score at Week 48 | -11.7 Score on a scale | Standard Error 1 |
Comparison: 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.p-value: 0.208495% CI: [-1.1, 5.2]MMRM
Secondary
Change From Baseline of Brain Volumes as Determined by MRI at 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).
Time frame: Baseline, Week 52
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Midbrain Volume: Change at Week 52 | -0.116 Cubic centimeter (cm^3) | Standard Error 0.008 |
| Placebo (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Cerebellar Peduncle Volume: Change at Week 52 | -0.005 Cubic centimeter (cm^3) | Standard Error 0.002 |
| Placebo (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Whole Brain Volume: Change at Week 52 | -18.612 Cubic centimeter (cm^3) | Standard Error 1.296 |
| Placebo (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Third Ventricle Volume: Change at Week 52 | 0.140 Cubic centimeter (cm^3) | Standard Error 0.014 |
| Placebo (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Pons Volume: Change at Week 52 | -0.198 Cubic centimeter (cm^3) | Standard Error 0.017 |
| Placebo (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Frontal Lobe Volume: Change at Week 52 | 1.184 Cubic centimeter (cm^3) | Standard Error 0.279 |
| Placebo (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Ventricles Volume: Change at Week 52 | 3.823 Cubic centimeter (cm^3) | Standard Error 0.302 |
| BIIB092 2000 mg (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Frontal Lobe Volume: Change at Week 52 | 1.143 Cubic centimeter (cm^3) | Standard Error 0.205 |
| BIIB092 2000 mg (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Ventricles Volume: Change at Week 52 | 3.802 Cubic centimeter (cm^3) | Standard Error 0.216 |
| BIIB092 2000 mg (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Whole Brain Volume: Change at Week 52 | -19.126 Cubic centimeter (cm^3) | Standard Error 0.95 |
| BIIB092 2000 mg (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Midbrain Volume: Change at Week 52 | -0.120 Cubic centimeter (cm^3) | Standard Error 0.006 |
| BIIB092 2000 mg (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Pons Volume: Change at Week 52 | -0.198 Cubic centimeter (cm^3) | Standard Error 0.012 |
| BIIB092 2000 mg (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Cerebellar Peduncle Volume: Change at Week 52 | -0.004 Cubic centimeter (cm^3) | Standard Error 0.002 |
| BIIB092 2000 mg (PC Period) | Change From Baseline of Brain Volumes as Determined by MRI at Week 52 | Third Ventricle Volume: Change at Week 52 | 0.146 Cubic centimeter (cm^3) | Standard Error 0.01 |
Comparison: 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.p-value: 0.952795% CI: [-0.726, 0.684]MMRM
Comparison: 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.p-value: 0.735795% CI: [-3.506, 2.478]MMRM
Comparison: 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.p-value: 0.643995% CI: [-0.023, 0.014]MMRM
Comparison: 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.p-value: 0.986495% CI: [-0.039, 0.04]MMRM
Comparison: 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.p-value: 0.752995% CI: [-0.004, 0.006]MMRM
Comparison: 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.p-value: 0.68595% CI: [-0.025, 0.038]MMRM
Comparison: 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.p-value: 0.995% CI: [-0.68, 0.598]MMRM
Secondary
Clinical Global Impression of Change (CGI-C) Scale Score
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PC Period) | Clinical Global Impression of Change (CGI-C) Scale Score | 5.3 Score on a scale | Standard Error 0.1 |
| BIIB092 2000 mg (PC Period) | Clinical Global Impression of Change (CGI-C) Scale Score | 5.2 Score on a scale | Standard Error 0.1 |
Comparison: 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.p-value: 0.774395% CI: [-0.2, 0.1]MMRM
Secondary
Number of Participants With Treatment Emergent Antibodies (Anti-BIIB092) Positive Results in Serum
Time frame: Up to Week 48
Population: ADA population - subset of the safety population with at least one evaluable post-baseline evaluable ADA samples.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (PC Period) | Number of Participants With Treatment Emergent Antibodies (Anti-BIIB092) Positive Results in Serum | 7 Participants |
| BIIB092 2000 mg (PC Period) | Number of Participants With Treatment Emergent Antibodies (Anti-BIIB092) Positive Results in Serum | 0 Participants |