E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to evaluate the efficacy of BIIB104 in subjects with Cognitive Impairment Associated with Schizophrenia (CIAS) using the Working Memory Domain of the MATRICS Consensus Cognitive Battery (MCCB). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of BIIB104 in subjects with CIAS. To evaluate the efficacy of BIIB104 in subjects with CIAS on measures of cognition, functioning, and psychiatric symptomology, as measured by: -University of California, San Diego Performance Based Skills Assessment–Brief, international version (UPSA-B, international version) -Schizophrenia Cognition Rating Scale (SCoRS) -MCCB -Positive and Negative Symptoms Scale (PANSS) -Clinical Global Impression–Severity (CGI-S) and Clinical Global Impression–Improvement (CGI-I) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Otherwise healthy participant with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), diagnosis of schizophrenia of at least 2 years’ duration as confirmed by the mini-international neuropsychiatric interview (MINI) 7.0.2 for Psychotic Disorders. - Evidence of stable schizophrenia symptomatology ≥12 weeks (e.g., no hospitalizations for schizophrenia, no increase in level of psychiatric care due to worsening of schizophrenia symptoms). - Participants must be in ongoing maintenance atypical antipsychotic therapy (except clozapine), on a stable treatment regimen for ≥8 weeks prior to Baseline/Day 1, including concomitant psychotropic medication. Doses of background atypical antipsychotics should be within the recommended dose range listed in the approved product labeling of the country where the study is being conducted. - SCI-PANSS: No more than moderate-severe rating (score ≤5) on delusions, hallucinatory behavior, grandiosity, suspiciousness / persecution, and hostility (i.e. PANSS, positive symptom items P1, P3, P5, P6, P7); or unusual thought content (G9); and no more than a moderate rating (score ≤4) on conceptual disorganization (P2). |
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E.4 | Principal exclusion criteria |
- Participation in a trial using any component or version of the MATRICS Consensus Cognitive Battery (MCCB) or the University of California, San Diego (UCSD) Performance-Based Skills Assessment test within the previous 6 months. - Participation in cognitive remediation therapy within 6 months prior to randomization - Screening MCCB Working Memory Domain T-score ≥60. - Current DSM-5 diagnosis of schizoaffective disorder on the MINI 7.0.2 for Psychotic Disorders. - Current DSM-5 diagnosis of major depressive episode, manic and hypomanic episode, panic disorder, agoraphobia, social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and/or generalized anxiety disorder on the MINI 7.0.2 for Psychotic Disorders. - Lifetime DSM-5 diagnosis of antisocial personality disorder, anorexia nervosa, bulimia nervosa, and/or binge-eating disorder on the MINI 7.0.2 for Psychotic Disorders. - Meets the DSM-5 diagnosis of moderate or severe substance use disorder (excluding nicotine dependence) within 12 months of screening on the MINI 7.0.2 for Psychotic Disorders interview. - DSM-5 diagnosis of Intellectual Disability (intellectual developmental disorder).
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in the MATRICS Consensus Cognitive Battery (MCCB) Working Memory Domain score to Week 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
-Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) -Change from Baseline in University of California, San Diego Performance Based Skills Assessment-Brief International Version (UPSA-Bi) Assessment to Week 12 -Change from Baseline in Schizophrenia Cognition Rating Scale (SCoRS) assessment to Week 12 -Change from Baseline in MCCB Composite and Individual Domain Scores (Excluding Working Memory Domain) to Week 12 -Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score and Subscale Scores to Week 12 -Change from Baseline in Clinical Global Impression-Severity (CGI-S) to Week 12 -Clinical Global Impression-Improvement (CGI-I) at Week 12 -Scale for the Assessment and Rating of Ataxia (SARA) Score -Columbia-Suicide Severity Rating Scale (CSSRS) score
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Up to Week 14 -Baseline, Week 12 -Baseline, Week 12 -Baseline, Week 12 -Baseline, Week 12 -Week 12 -Up to Week 14 -Up to Week 14 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Germany |
Japan |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |