Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of BIIB104 in Participants With Cognitive Impairment Associated With Schizophrenia (CIAS) (NCT NCT03745820)

NCT ID: NCT03745820

Last Updated: 2023-04-18

Results Overview

The MCCB is a cognitive battery that assesses 7 domains recommended by the MATRICS initiative (i.e., Working Memory, Verbal Learning, Speed of Processing, Attention/Vigilance, Visual Learning, Social Cognition, and Reasoning and Problem Solving). MCCB was administered via laptop computer and paper-and-pencil assessments. T-scores for the individual tests were calculated according to the developer's recommended scoring algorithms. MCCB composite T scores are between 40 and 60 (normal range). Higher scores indicate better cognitive functioning. The working memory domain score of the MCCB is reported in this outcome measure.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 195 participants
• Primary outcome timeframe: Baseline and Week 12
• Results posted on: 2023-04-18

Participant Flow

Participants took part in the study at 53 investigative sites in the United States, Japan, Spain, Germany, and the United Kingdom from 15 Nov 2018 to 07 April 2022.

A total of 554 participants were screened out of which, 195 participants were randomized and dosed to receive BIIB104 or placebo.

Participant milestones

Measure	Placebo Participants received BIIB104 matching placebo capsules, twice a day (BID), orally for 12 weeks.	BIIB104 0.15 mg Participants received 0.15 milligrams (mg) capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Overall Study STARTED	64	66	65
Overall Study Safety Analysis Set	63	66	66
Overall Study COMPLETED	52	52	51
Overall Study NOT COMPLETED	12	14	14

Reasons for withdrawal

Measure	Placebo Participants received BIIB104 matching placebo capsules, twice a day (BID), orally for 12 weeks.	BIIB104 0.15 mg Participants received 0.15 milligrams (mg) capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Overall Study Adverse Event	0	3	2
Overall Study Non-Compliance with Study Drug	4	3	0
Overall Study Withdrawal by Subject	4	4	4
Overall Study Physician decision unrelated to safety/efficacy	0	0	4
Overall Study Lost to Follow-up	2	0	3
Overall Study Reason not Specified	2	4	1

Baseline Characteristics

A Study to Evaluate the Safety and Efficacy of BIIB104 in Participants With Cognitive Impairment Associated With Schizophrenia (CIAS)

Baseline characteristics by cohort

Measure	Placebo n=64 Participants Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=66 Participants Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=65 Participants Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.	Total n=195 Participants Total of all reporting groups
Age, Continuous	40.6 years STANDARD_DEVIATION 9.47 • n=5 Participants	37.7 years STANDARD_DEVIATION 9.41 • n=7 Participants	41.3 years STANDARD_DEVIATION 9.63 • n=5 Participants	39.8 years STANDARD_DEVIATION 9.58 • n=4 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	21 Participants n=7 Participants	18 Participants n=5 Participants	59 Participants n=4 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	45 Participants n=7 Participants	47 Participants n=5 Participants	136 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	9 Participants n=7 Participants	6 Participants n=5 Participants	25 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=5 Participants	47 Participants n=7 Participants	49 Participants n=5 Participants	141 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	29 Participants n=4 Participants
Race/Ethnicity, Customized Asian	10 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants	31 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	29 Participants n=5 Participants	27 Participants n=7 Participants	26 Participants n=5 Participants	82 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized White	15 Participants n=5 Participants	19 Participants n=7 Participants	15 Participants n=5 Participants	49 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	9 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	29 Participants n=4 Participants
MATRICS Consensus Cognitive Battery (MCCB) Working Memory Domain Score	39.6 score on a scale n=5 Participants	38.5 score on a scale n=7 Participants	39.8 score on a scale n=5 Participants	39.3 score on a scale n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: ITT population included all randomized participants who received at least one dose of study treatment (BIIB104 or placebo). Here, "Overall Number of Participants Analyzed" signifies the number of participants analyzed in this outcome measure.

The MCCB is a cognitive battery that assesses 7 domains recommended by the MATRICS initiative (i.e., Working Memory, Verbal Learning, Speed of Processing, Attention/Vigilance, Visual Learning, Social Cognition, and Reasoning and Problem Solving). MCCB was administered via laptop computer and paper-and-pencil assessments. T-scores for the individual tests were calculated according to the developer's recommended scoring algorithms. MCCB composite T scores are between 40 and 60 (normal range). Higher scores indicate better cognitive functioning. The working memory domain score of the MCCB is reported in this outcome measure.

Outcome measures

Measure	Placebo n=50 Participants Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=50 Participants Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=49 Participants Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Change From Baseline in Change From Baseline in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Working Memory Domain Score at Week 12	1.17 score on a scale Standard Error 0.939	0.91 score on a scale Standard Error 0.936	0.84 score on a scale Standard Error 0.934

SECONDARY outcome

Timeframe: From first dose of study drug through end of the study (up to Week 14)

Population: The safety population included all randomized participants who received at least 1 dose of study treatment (BIIB104 or placebo).

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event.

Outcome measures

Measure	Placebo n=63 Participants Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=66 Participants Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=66 Participants Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	28 Participants	32 Participants	28 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 6, 12 and safety follow-up (Week 14)

Population: The safety population included all randomized participants who received at least 1 dose of study treatment (BIIB104 or placebo). Here, "Overall number of participants analyzed" signifies the number of participants analyzed in this outcome measure and "number analyzed" signifies the number of participants analyzed at specified time-point.

The SARA is a clinical scale that is based on a semiquantitative assessment of cerebellar ataxia on an impairment level and complements the brief neurological examination. The SARA scale is an eight-item clinical rating scale (gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements, and heel-shin test) with a total score range of 0-40, where 0 is the best neurological status and 40 is the worst neurological status.

Outcome measures

Measure	Placebo n=62 Participants Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=64 Participants Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=65 Participants Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Mean Total Score Assessed by Scale for the Assessment and Rating of Ataxia (SARA) Baseline	0.5 score on a scale Standard Deviation 1.03	0.4 score on a scale Standard Deviation 1.15	0.3 score on a scale Standard Deviation 0.92
Mean Total Score Assessed by Scale for the Assessment and Rating of Ataxia (SARA) Week 2	0.4 score on a scale Standard Deviation 0.85	0.5 score on a scale Standard Deviation 1.10	0.3 score on a scale Standard Deviation 0.68
Mean Total Score Assessed by Scale for the Assessment and Rating of Ataxia (SARA) Week 6	0.4 score on a scale Standard Deviation 0.71	0.3 score on a scale Standard Deviation 0.90	0.2 score on a scale Standard Deviation 0.58
Mean Total Score Assessed by Scale for the Assessment and Rating of Ataxia (SARA) Week 12	0.4 score on a scale Standard Deviation 0.80	0.3 score on a scale Standard Deviation 0.82	0.2 score on a scale Standard Deviation 0.72
Mean Total Score Assessed by Scale for the Assessment and Rating of Ataxia (SARA) Week 14	0.4 score on a scale Standard Deviation 0.85	0.3 score on a scale Standard Deviation 0.91	0.2 score on a scale Standard Deviation 0.69

SECONDARY outcome

Timeframe: Up to Week 14

Population: The safety population included all randomized participants who received at least 1 dose of study treatment (BIIB104 or placebo). Here, "Overall Number of Participants Analyzed" signifies the number of participants analyzed in this outcome measure.

The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. Suicidal ideation is classified on a 5-item scale: 1 (wish to be dead), 2 (nonspecific active suicidal thoughts), 3 (active suicidal ideation with any methods [not plan] without intent to act), 4 (active suicidal ideation with some intent to act, without specific plan), and 5 (active suicidal ideation with specific plan and intent). Suicidal behavior is classified on a 6-item scale: 1 (actual attempt), 2 (interrupted attempt), 3 (aborted attempt), 4 (preparatory acts or behavior), 5 (suicidal behavior), and 6 (suicide). The data analyzed signifies the participants with at least one event of suicidal ideation and/or suicidal behavior.

Outcome measures

Measure	Placebo n=63 Participants Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=65 Participants Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=65 Participants Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Number of Participants With at Least One Event of Suicidal Ideation and/or Suicidal Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score	3 Participants	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT population included all randomized participants who received at least one dose of study treatment (BIIB104 or placebo). Here, "Overall Number of Participants Analyzed" signifies the number of participants analyzed in this outcome measure.

The UPSA-Bi, international version, an abbreviated version of the UPSA-Validation of Intermediate Measures, is a measure of functional capacity and assesses skills used in community tasks. This assessment measures 2 general skills that were previously identified as essential to functioning in the community: financial skills and communication skills. The UPSA-Bi assessment is scored from 0-100, higher scores indicating higher functional status.

Outcome measures

Measure	Placebo n=49 Participants Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=50 Participants Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=49 Participants Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Change From Baseline in University of California, San Diego Performance Based Skills Assessment-Brief International Version (UPSA-Bi) Assessment at Week 12	2.07 score on a scale Standard Error 1.303	5.50 score on a scale Standard Error 1.292	5.49 score on a scale Standard Error 1.305

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT population included all randomized participants who received at least one dose of study treatment (BIIB104 or placebo). Here, "Overall Number of Participants Analyzed" signifies the number of participants analyzed in this outcome measure.

The SCoRS is an interview-based assessment of cognition that involves interviews with participants and informants. The SCoRS includes 20 items designed to specifically assess aspects of cognitive functioning found in each of the seven MCCB cognitive domains including the following: Memory: 4 items; Learning: 2 items; Attention: 3 items; Working memory: 2 items; Problem solving: 3 items; Processing/motor speed: 2 items; Social cognition: 3 items; Language: 1 item. Total score range is 20-80, lower scores indicating higher functional status. The data reported in this outcome measure are for global rating score.

Outcome measures

Measure	Placebo n=49 Participants Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=48 Participants Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=50 Participants Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Change From Baseline in Schizophrenia Cognition Rating Scale (SCoRS) Assessment Score at Week 12	-0.51 score on a scale Standard Error 0.146	-0.42 score on a scale Standard Error 0.148	-0.41 score on a scale Standard Error 0.145

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT population included all randomized participants who received at least one dose of study treatment (BIIB104 or placebo). Here, "Overall Number of Participants Analyzed" signifies the number of participants analyzed in this outcome measure.

The MCCB is a cognitive battery that assesses 7 domains recommended by the MATRICS initiative (i.e., Working Memory, Verbal Learning, Speed of Processing, Attention/Vigilance, Visual Learning, Social Cognition, and Reasoning and Problem Solving). MCCB was administered via laptop computer and paper-and-pencil assessments. T-scores for the individual tests were calculated according to the developer's recommended scoring algorithms. MCCB composite T scores are between 40 and 60 (normal range). Higher scores indicate better cognitive functioning. The MCCB composite score contains all of the tests and domains of the MCCB.

Outcome measures

Measure	Placebo n=50 Participants Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=50 Participants Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=49 Participants Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Change From Baseline in MCCB Neurocognitive Composite Scores at Week 12	2.90 score on a scale Standard Error 0.733	1.80 score on a scale Standard Error 0.728	3.39 score on a scale Standard Error 0.727

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT population included all randomized participants who received at least one dose of study treatment (BIIB104 or placebo). Here, "Overall Number of Participants Analyzed" signifies the number of participants analyzed in this outcome measure.

The MCCB is a cognitive battery that assesses 7 domains recommended by the MATRICS initiative (i.e., working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, and reasoning and problem solving). MCCB was administered via laptop computer and paper-and-pencil assessments. T-scores for the individual tests were calculated according to the developer's recommended scoring algorithms. MCCB composite T scores are between 40 and 60 (normal range). Higher scores indicate better cognitive functioning. All the domain scores of the MCCB are reported in this outcome measure with the exception of working memory domain.

Outcome measures

Measure	Placebo n=50 Participants Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=50 Participants Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=49 Participants Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Change From Baseline in MCCB Individual Domain Scores (Excluding Working Memory Domain) at Week 12 Verbal Learning: Change at Week 12	0.95 score on a scale Standard Error 0.951	1.41 score on a scale Standard Error 0.946	0.41 score on a scale Standard Error 0.950
Change From Baseline in MCCB Individual Domain Scores (Excluding Working Memory Domain) at Week 12 Speed of Processing: Change at Week 12	4.42 score on a scale Standard Error 0.824	2.28 score on a scale Standard Error 0.819	3.99 score on a scale Standard Error 0.817
Change From Baseline in MCCB Individual Domain Scores (Excluding Working Memory Domain) at Week 12 Attention/Vigilance: Change at Week 12	0.62 score on a scale Standard Error 0.852	0.53 score on a scale Standard Error 0.848	1.55 score on a scale Standard Error 0.848
Change From Baseline in MCCB Individual Domain Scores (Excluding Working Memory Domain) at Week 12 Visual Learning: Change at Week 12	1.70 score on a scale Standard Error 1.131	0.19 score on a scale Standard Error 1.125	1.77 score on a scale Standard Error 1.125
Change From Baseline in MCCB Individual Domain Scores (Excluding Working Memory Domain) at Week 12 Social Cognition: Change at Week 12	-0.13 score on a scale Standard Error 0.959	1.06 score on a scale Standard Error 0.953	0.95 score on a scale Standard Error 0.955
Change From Baseline in MCCB Individual Domain Scores (Excluding Working Memory Domain) at Week 12 Reasoning and Problem Solving: Change at Week 12	2.81 score on a scale Standard Error 1.019	2.10 score on a scale Standard Error 1.1014	4.40 score on a scale Standard Error 1.011

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT population included all randomized participants who received at least one dose of study treatment (BIIB104 or placebo). Here, "Overall Number of Participants Analyzed" signifies the number of participants analyzed in this outcome measure.

The PANSS includes 3 subscales and 30 items: 7 items that make up the Positive subscale (e.g., delusions, conceptual disorganization, hallucinatory behaviour); 7 items that make up the Negative subscale (e.g., blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal); and 16 items that make up the General Psychopathology subscale (e.g., somatic concern, anxiety, guilt feelings, mannerisms and posturing, motor retardation, uncooperativeness, disorientation, poor impulse control, preoccupation). Each item on the positive, negative and general psychopathology subscale is rated from 1 (absent) to 7 (extreme). The score range is 7-49 for positive and negative subscales, score range is 16-112 for the general psychopathology subscale. Total PANSS score (positive+ negative + general psychopathology subscale scores) range from 30 to 210. Higher scores represent more severity in symptoms.

Outcome measures

Measure	Placebo n=51 Participants Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=51 Participants Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=50 Participants Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score, Positive Subscale, and Negative Subscale Scores at Week 12 Positive Symptoms Subscale: Change From Baseline at Week 12	-0.65 score on a scale Standard Error 0.431	-1.09 score on a scale Standard Error 0.430	-0.98 score on a scale Standard Error 0.429
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score, Positive Subscale, and Negative Subscale Scores at Week 12 Negative Symptoms Subscale: Change From Baseline at Week 12	-0.90 score on a scale Standard Error 0.461	-0.98 score on a scale Standard Error 0.461	-1.40 score on a scale Standard Error 0.460
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score, Positive Subscale, and Negative Subscale Scores at Week 12 Total Score: Change From Baseline at Week 12	-3.06 score on a scale Standard Error 1.429	-4.26 score on a scale Standard Error 1.421	-5.03 score on a scale Standard Error 1.427

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT population included all randomized participants who received at least one dose of study treatment (BIIB104 or placebo). Here, "Overall Number of Participants Analyzed" signifies the number of participants analyzed in this outcome measure.

The CGI-S consists of a single 7-point rating score of illness severity. The following question: "Considering your total clinical experience with this particular population, how mentally ill is your participant at this time?" is rated with a score from 1 to 7- 1: Normal, not ill at all; 2: Borderline mentally ill; 3: Mildly ill; 4: Moderately ill; 5: Markedly ill; 6: Severely ill; or 7: Among the most severely ill participants. Lower scores indicate less severity of illness.

Outcome measures

Measure	Placebo n=51 Participants Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=50 Participants Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=50 Participants Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scores at Week 12	-0.19 score on a scale Standard Error 0.091	-0.16 score on a scale Standard Error 0.091	-0.19 score on a scale Standard Error 0.091

SECONDARY outcome

Timeframe: Week 12

Population: ITT population included all randomized participants who received at least one dose of study treatment (BIIB104 or placebo). Here, "Overall Number of Participants Analyzed" signifies the number of participants analyzed in this outcome measure.

The CGI-I consists of a single 7-point rating score total improvement, regardless of whether or not the change is due entirely to drug treatment. The following question: "Compared to your participant's condition at the beginning of treatment, how much has your participant changed?" is rated with a score from 1 to 7- 1: Very much improved; 2: Much improved; 3: Minimally improved; 4: No change; 5: Minimally worse; 6: Much worse; or 7: Very much worse. Lower scores indicate greater improvement.

Outcome measures

Measure	Placebo n=51 Participants Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=50 Participants Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=50 Participants Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Number of Participants With Response on Clinical Global Impression-Improvement (CGI-I) Scale at Week 12 Very Much Improved	1 Participants	1 Participants	0 Participants
Number of Participants With Response on Clinical Global Impression-Improvement (CGI-I) Scale at Week 12 Much Improved	11 Participants	4 Participants	4 Participants
Number of Participants With Response on Clinical Global Impression-Improvement (CGI-I) Scale at Week 12 Minimally Improved	13 Participants	18 Participants	18 Participants
Number of Participants With Response on Clinical Global Impression-Improvement (CGI-I) Scale at Week 12 No Change	22 Participants	26 Participants	26 Participants
Number of Participants With Response on Clinical Global Impression-Improvement (CGI-I) Scale at Week 12 Minimally Worse	2 Participants	1 Participants	2 Participants
Number of Participants With Response on Clinical Global Impression-Improvement (CGI-I) Scale at Week 12 Much Worse	2 Participants	0 Participants	0 Participants
Number of Participants With Response on Clinical Global Impression-Improvement (CGI-I) Scale at Week 12 Very Much Worse	0 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

BIIB104 0.15 mg

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

BIIB104 0.5 mg

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=63 participants at risk Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=66 participants at risk Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=66 participants at risk Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Infections and infestations Appendicitis	1.6% 1/63 • Number of events 1 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.	0.00% 0/66 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.	0.00% 0/66 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.
Psychiatric disorders Schizophrenia	0.00% 0/63 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.	1.5% 1/66 • Number of events 1 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.	1.5% 1/66 • Number of events 2 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.
Psychiatric disorders Psychiatric decompensation	0.00% 0/63 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.	0.00% 0/66 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.	1.5% 1/66 • Number of events 1 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.

Other adverse events

Measure	Placebo n=63 participants at risk Participants received BIIB104 matching placebo capsules, BID, orally for 12 weeks.	BIIB104 0.15 mg n=66 participants at risk Participants received 0.15 mg capsules of BIIB104, BID, orally for 12 weeks.	BIIB104 0.5 mg n=66 participants at risk Participants received 0.5 mg capsules of BIIB104, BID, orally for 12 weeks.
Nervous system disorders Headache	1.6% 1/63 • Number of events 1 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.	1.5% 1/66 • Number of events 1 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.	6.1% 4/66 • Number of events 4 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.
Psychiatric disorders Schizophrenia	1.6% 1/63 • Number of events 1 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.	1.5% 1/66 • Number of events 1 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.	6.1% 4/66 • Number of events 4 • From first dose of study drug through end of the study (up to Week 14) The safety population included all randomized participants who received at least 1 dose of study treatment(BIIB104 or placebo).One participant randomized to placebo,inadvertently received one or more doses of active treatment. For participants affected, a participant was counted only once within each system organ class/preferred term/study period.

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: clinicaltrials@biogen.com

Results disclosure agreements

• Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for non-commercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
• Publication restrictions are in place

Restriction type: OTHER