A Phase 2 interventional study of BIIB104 and Placebo in Cognitive Impairment Associated With Schizophrenia, sponsored by Biogen. Completed at 60 sites in 5 countries. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2023-04-18.
Sponsored by Biogen · Phase 2, Interventional, and Treatment
The primary objective of the study is to evaluate the efficacy of BIIB104 in participants with CIAS, using the Working Memory Domain of the MATRICS Consensus Cognitive Battery (MCCB).
The secondary objectives of this study are to evaluate the safety and tolerability of BIIB104 in participants with CIAS, and to evaluate the efficacy of BIIB104 in participants with CIAS on measures of cognition, functioning, and psychiatric symptomology.
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Key Inclusion Criteria:
Key Exclusion Criteria:
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Participants will receive 0.5 mg of BIIB104 twice a day, orally, for 12 weeks.
Drug: BIIB104
Participants will receive 0.15 mg of BIIB104 twice a day, orally, for 12 weeks.
Drug: BIIB104
Participants will receive matching placebo twice a day, orally, for 12 weeks.
Other: Placebo
Administered as specified in the treatment arm
Also known as: PF-04958242
Administered as specified in the treatment arm
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
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.
Time frame: Baseline and Week 12
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: From first dose of study drug through end of the study (up to Week 14)
Mean Total Score Assessed by Scale for the Assessment and Rating of Ataxia (SARA)
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.
Time frame: Baseline, Weeks 2, 6, 12 and safety follow-up (Week 14)
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
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.
Time frame: Up to Week 14
Change From Baseline in University of California, San Diego Performance Based Skills Assessment-Brief International Version (UPSA-Bi) Assessment at Week 12
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.
Time frame: Baseline and Week 12
Change From Baseline in Schizophrenia Cognition Rating Scale (SCoRS) Assessment Score at Week 12
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.
Time frame: Baseline and Week 12
Change From Baseline in MCCB Neurocognitive Composite Scores at Week 12
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.
Time frame: Baseline and Week 12
Change From Baseline in MCCB Individual Domain Scores (Excluding Working Memory Domain) at Week 12
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.
Time frame: Baseline and Week 12
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score, Positive Subscale, and Negative Subscale Scores at Week 12
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.
Time frame: Baseline and Week 12
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scores at Week 12
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.
Time frame: Baseline and Week 12
Number of Participants With Response on Clinical Global Impression-Improvement (CGI-I) Scale at Week 12
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.
Time frame: Week 12
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.
| Milestone | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| Started | 64 | 66 | 65 |
| Safety analysis set | 63 | 66 | 66 |
| Completed | 52 | 52 | 51 |
| Not completed | 12 | 14 | 14 |
| Withdrew: Adverse event | 0 | 3 | 2 |
| Withdrew: Non-compliance with study drug | 4 | 3 | 0 |
| Withdrew: Withdrawal by subject | 4 | 4 | 4 |
| Withdrew: Physician decision unrelated to safety/efficacy | 0 | 0 | 4 |
| Withdrew: Lost to follow-up | 2 | 0 | 3 |
| Withdrew: Reason not specified | 2 | 4 | 1 |
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.
| score on a scale | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| 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 ± 0.939 | 0.91 ± 0.936 | 0.84 ± 0.934 |
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.
| Participants | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| AEs | 28 | 32 | 28 |
| SAEs | 1 | 1 | 2 |
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.
| score on a scale | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| Baseline | 0.5 ± 1.03 | 0.4 ± 1.15 | 0.3 ± 0.92 |
| Week 2 | 0.4 ± 0.85 | 0.5 ± 1.10 | 0.3 ± 0.68 |
| Week 6 | 0.4 ± 0.71 | 0.3 ± 0.90 | 0.2 ± 0.58 |
| Week 12 | 0.4 ± 0.80 | 0.3 ± 0.82 | 0.2 ± 0.72 |
| Week 14 | 0.4 ± 0.85 | 0.3 ± 0.91 | 0.2 ± 0.69 |
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.
| Participants | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| 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 | 4 | 0 |
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.
| score on a scale | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| Change From Baseline in University of California, San Diego Performance Based Skills Assessment-Brief International Version (UPSA-Bi) Assessment at Week 12 | 2.07 ± 1.303 | 5.50 ± 1.292 | 5.49 ± 1.305 |
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.
| score on a scale | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| Change From Baseline in Schizophrenia Cognition Rating Scale (SCoRS) Assessment Score at Week 12 | -0.51 ± 0.146 | -0.42 ± 0.148 | -0.41 ± 0.145 |
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.
| score on a scale | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| Change From Baseline in MCCB Neurocognitive Composite Scores at Week 12 | 2.90 ± 0.733 | 1.80 ± 0.728 | 3.39 ± 0.727 |
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.
| score on a scale | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| Verbal Learning: Change at Week 12 | 0.95 ± 0.951 | 1.41 ± 0.946 | 0.41 ± 0.950 |
| Speed of Processing: Change at Week 12 | 4.42 ± 0.824 | 2.28 ± 0.819 | 3.99 ± 0.817 |
| Attention/Vigilance: Change at Week 12 | 0.62 ± 0.852 | 0.53 ± 0.848 | 1.55 ± 0.848 |
| Visual Learning: Change at Week 12 | 1.70 ± 1.131 | 0.19 ± 1.125 | 1.77 ± 1.125 |
| Social Cognition: Change at Week 12 | -0.13 ± 0.959 | 1.06 ± 0.953 | 0.95 ± 0.955 |
| Reasoning and Problem Solving: Change at Week 12 | 2.81 ± 1.019 | 2.10 ± 1.1014 | 4.40 ± 1.011 |
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.
| score on a scale | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| Positive Symptoms Subscale: Change From Baseline at Week 12 | -0.65 ± 0.431 | -1.09 ± 0.430 | -0.98 ± 0.429 |
| Negative Symptoms Subscale: Change From Baseline at Week 12 | -0.90 ± 0.461 | -0.98 ± 0.461 | -1.40 ± 0.460 |
| Total Score: Change From Baseline at Week 12 | -3.06 ± 1.429 | -4.26 ± 1.421 | -5.03 ± 1.427 |
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.
| score on a scale | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scores at Week 12 | -0.19 ± 0.091 | -0.16 ± 0.091 | -0.19 ± 0.091 |
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.
| Participants | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| Very Much Improved | 1 | 1 | 0 |
| Much Improved | 11 | 4 | 4 |
| Minimally Improved | 13 | 18 | 18 |
| No Change | 22 | 26 | 26 |
| Minimally Worse | 2 | 1 | 2 |
| Much Worse | 2 | 0 | 0 |
| Very Much Worse | 0 | 0 | 0 |
Collected over From first dose of study drug through end of the study (up to Week 14). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/63 (0%) | 1/63 (1.6%) | 2/63 (3.2%) |
| BIIB104 0.15 mg | 0/66 (0%) | 1/66 (1.5%) | 2/66 (3%) |
| BIIB104 0.5 mg | 0/66 (0%) | 2/66 (3%) | 8/66 (12.1%) |
| Event | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| AppendicitisInfections and infestations | 1/63 | 0/66 | 0/66 |
| SchizophreniaPsychiatric disorders | 0/63 | 1/66 | 1/66 |
| Psychiatric decompensationPsychiatric disorders | 0/63 | 0/66 | 1/66 |
| Event | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg |
|---|---|---|---|
| HeadacheNervous system disorders | 1/63 | 1/66 | 4/66 |
| SchizophreniaPsychiatric disorders | 1/63 | 1/66 | 4/66 |
Intent-to-treat (ITT) population included all randomized participants who received at least one dose of study treatment (BIIB104 or placebo).
| Age, Continuous(years) | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg | Total |
|---|---|---|---|---|
| Mean | 40.6 ± 9.47 | 37.7 ± 9.41 | 41.3 ± 9.63 | 39.8 ± 9.58 |
| Sex: Female, Male(Participants) | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg | Total |
|---|---|---|---|---|
| Female | 20 | 21 | 18 | 59 |
| Male | 44 | 45 | 47 | 136 |
| Ethnicity (NIH/OMB)(Participants) | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg | Total |
|---|---|---|---|---|
| Hispanic or Latino | 10 | 9 | 6 | 25 |
| Not Hispanic or Latino | 45 | 47 | 49 | 141 |
| Unknown or Not Reported | 9 | 10 | 10 | 29 |
| Race/Ethnicity, Customized(Participants) | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg | Total |
|---|---|---|---|---|
| Asian | 10 | 8 | 13 | 31 |
| Black or African American | 29 | 27 | 26 | 82 |
| Native Hawaiian or Other Pacific Islander | 1 | 0 | 1 | 2 |
| White | 15 | 19 | 15 | 49 |
| Other | 0 | 2 | 0 | 2 |
| Unknown | 9 | 10 | 10 | 29 |
| MATRICS Consensus Cognitive Battery (MCCB) Working Memory Domain Score(score on a scale) | Placebo | BIIB104 0.15 mg | BIIB104 0.5 mg | Total |
|---|---|---|---|---|
| Mean | 39.6 (17 to 70) | 38.5 (12 to 60) | 39.8 (17 to 58) | 39.3 (12 to 70) |
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