Trial Outcomes & Findings for Study of BIIB092 in Participants With Progressive Supranuclear Palsy (NCT NCT03068468)

Last Updated: 2020-12-21

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

490 participants

Primary outcome timeframe

Baseline, Week 52

Results posted on

2020-12-21

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.	BIIB092 Late Start (OLE 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.	BIIB092 Early Start (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.
Placebo-Controlled Period STARTED	166	324	0	0
Placebo-Controlled Period Treated	165	321	0	0
Placebo-Controlled Period COMPLETED	144	279	0	0
Placebo-Controlled Period NOT COMPLETED	22	45	0	0
Open-Label Extension Period STARTED	0	0	140	276
Open-Label Extension Period COMPLETED	0	0	0	0
Open-Label Extension Period NOT COMPLETED	0	0	140	276

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	BIIB092 Late Start (OLE 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.	BIIB092 Early Start (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.
Placebo-Controlled Period Randomized but not Treated	1	3	0	0
Placebo-Controlled Period Lack of Efficacy	0	1	0	0
Placebo-Controlled Period Adverse Event	16	21	0	0
Placebo-Controlled Period Withdrawal by Subject	3	11	0	0
Placebo-Controlled Period Withdrawal by Parent/Guardian	1	2	0	0
Placebo-Controlled Period Reason Not Specified	1	6	0	0
Placebo-Controlled Period Death	0	1	0	0
Open-Label Extension Period Lack of Efficacy	0	0	1	2
Open-Label Extension Period Adverse Event	0	0	13	17
Open-Label Extension Period Withdrawal by Subject	0	0	7	20
Open-Label Extension Period Death	0	0	0	1
Open-Label Extension Period Lost to Follow-up	0	0	1	0
Open-Label Extension Period Failure to Meet Randomization Criteria	0	0	2	0
Open-Label Extension Period Withdrawal by Sponsor	0	0	115	228
Open-Label Extension Period Withdrawal by Parent/Guardian	0	0	0	4
Open-Label Extension Period Reason not Specified	0	0	1	4

Baseline Characteristics

Study of BIIB092 in Participants With Progressive Supranuclear Palsy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (PC Period) n=165 Participants 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.	BIIB092 2000 mg (PC Period) n=321 Participants 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 n=486 Participants Total of all reporting groups
Age, Continuous	68.9 years STANDARD_DEVIATION 6.57 • n=5 Participants	68.7 years STANDARD_DEVIATION 7.02 • n=7 Participants	68.7 years STANDARD_DEVIATION 6.86 • n=5 Participants
Sex: Female, Male Female	74 Participants n=5 Participants	136 Participants n=7 Participants	210 Participants n=5 Participants
Sex: Female, Male Male	91 Participants n=5 Participants	185 Participants n=7 Participants	276 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	117 Participants n=5 Participants	242 Participants n=7 Participants	359 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	43 Participants n=5 Participants	72 Participants n=7 Participants	115 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	138 Participants n=5 Participants	281 Participants n=7 Participants	419 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian Indian	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Race · Chinese	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Japanese	16 Participants n=5 Participants	23 Participants n=7 Participants	39 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian Other	4 Participants n=5 Participants	10 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Race · Unknown	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=139 Participants 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.	BIIB092 2000 mg (PC Period) n=278 Participants 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.
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	10.4 Score on a scale Standard Error 0.6
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	7.29 Score on a scale Standard Error 0.38

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=162 Participants 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.	BIIB092 2000 mg (PC Period) n=324 Participants 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.
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	4.9 Percentage of participants
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	27.2 Percentage of participants
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	92.9 Percentage of participants
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	7.4 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=143 Participants 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.	BIIB092 2000 mg (PC Period) n=270 Participants 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.
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	7.0 Score on a scale Standard Error 0.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=138 Participants 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.	BIIB092 2000 mg (PC Period) n=271 Participants 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.
Clinical Global Impression of Change (CGI-C) Scale Score	5.3 Score on a scale Standard Error 0.1	5.2 Score on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=134 Participants 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.	BIIB092 2000 mg (PC Period) n=249 Participants 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.
Change From Baseline in Progressive Supranuclear Palsy (PSP)-Cognitive Composite Battery Z-Score at Week 52	-0.283 z-score Standard Error 0.032	-0.245 z-score Standard Error 0.024

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=111 Participants 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.	BIIB092 2000 mg (PC Period) n=222 Participants 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.
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	-3.2 Score on a scale Standard Error 0.5

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=142 Participants 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.	BIIB092 2000 mg (PC Period) n=264 Participants 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.
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	11.2 Score on a scale Standard Error 1.1
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	6.1 Score on a scale Standard Error 1.0
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	-5.4 Score on a scale Standard Error 1.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=140 Participants 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.	BIIB092 2000 mg (PC Period) n=277 Participants 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.
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	-11.7 Score on a scale Standard Error 1.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=140 Participants 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.	BIIB092 2000 mg (PC Period) n=269 Participants 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.
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	0.6 Score on a scale Standard Error 0.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=141 Participants 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.	BIIB092 2000 mg (PC Period) n=273 Participants 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.
Change From Baseline in Phonemic Fluency Test Score at Week 48	-0.9 Score on a scale Standard Deviation 0.4	0.0 Score on a scale Standard Deviation 0.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=139 Participants 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.	BIIB092 2000 mg (PC Period) n=271 Participants 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.
Change From Baseline in Letter-Number Sequencing Test at Week 48	-1.9 Score on a scale Standard Error 0.4	-1.1 Score on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=143 Participants 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.	BIIB092 2000 mg (PC Period) n=279 Participants 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.
Change From Baseline in Color Trails at Week 48 Color Trails Test 1	16.8 Seconds Standard Error 3.6	16.9 Seconds Standard Error 2.7
Change From Baseline in Color Trails at Week 48 Color Trails Test 2	10.6 Seconds Standard Error 2.4	10.5 Seconds Standard Error 1.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=136 Participants 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.	BIIB092 2000 mg (PC Period) n=264 Participants 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.
Change From Baseline in Montreal Cognitive Assessment (MoCA) Score at Week 48	-1.0 Score on a scale Standard Error 0.3	-0.5 Score on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Up to Week 48

Population: ADA population - subset of the safety population with at least one evaluable post-baseline evaluable ADA samples.

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=160 Participants 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.	BIIB092 2000 mg (PC Period) n=323 Participants 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.
Number of Participants With Treatment Emergent Antibodies (Anti-BIIB092) Positive Results in Serum	7 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo (PC Period) n=114 Participants 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.	BIIB092 2000 mg (PC Period) n=238 Participants 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.
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	-0.198 Cubic centimeter (cm^3) Standard Error 0.012
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	3.802 Cubic centimeter (cm^3) Standard Error 0.216
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	-19.126 Cubic centimeter (cm^3) Standard Error 0.950
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	-0.120 Cubic centimeter (cm^3) Standard Error 0.006
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	-0.004 Cubic centimeter (cm^3) Standard Error 0.002
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	0.146 Cubic centimeter (cm^3) Standard Error 0.010
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	1.143 Cubic centimeter (cm^3) Standard Error 0.205

Adverse Events

Placebo (Placebo Controlled Period)

Serious events: 52 serious events

Other events: 127 other events

Deaths: 8 deaths

BIIB092 2000 mg (Placebo Controlled Period)

Serious events: 88 serious events

Other events: 235 other events

Deaths: 16 deaths

BIIB092 Late Start (Open-label Extension Period)

Serious events: 40 serious events

Other events: 69 other events

Deaths: 10 deaths

BIIB092 Early Start (Open-label Extension Period)

Serious events: 63 serious events

Other events: 130 other events

Deaths: 16 deaths

Serious adverse events

Other adverse events

Additional Information

Biogen Study Medical Director

Biogen

Phone: 866-633-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER