A Study to Evaluate the Safety and Efficacy of BIIB104 in Participants With Cognitive Impairment Associated With Schizophrenia (CIAS)
- Conditions
- Cognitive Impairment Associated With Schizophrenia
- Interventions
- Other: Placebo
- Registration Number
- NCT03745820
- Lead Sponsor
- Biogen
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 195
- 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).
Key
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BIIB104 0.5 mg BIIB104 Participants will receive 0.5 mg of BIIB104 twice a day, orally, for 12 weeks. BIIB104 0.15 mg BIIB104 Participants will receive 0.15 mg of BIIB104 twice a day, orally, for 12 weeks. Matching Placebo Placebo Participants will receive matching placebo twice a day, orally, for 12 weeks.
- Primary Outcome Measures
Name Time Method 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 Baseline and 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From first dose of study drug through end of the study (up to Week 14) 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.
Change From Baseline in Schizophrenia Cognition Rating Scale (SCoRS) Assessment Score at Week 12 Baseline and 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.
Change From Baseline in MCCB Neurocognitive Composite Scores at Week 12 Baseline and 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.
Mean Total Score Assessed by Scale for the Assessment and Rating of Ataxia (SARA) Baseline, Weeks 2, 6, 12 and safety follow-up (Week 14) 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.
Change From Baseline in MCCB Individual Domain Scores (Excluding Working Memory Domain) at Week 12 Baseline and 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.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score, Positive Subscale, and Negative Subscale Scores at Week 12 Baseline and 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.
Change From Baseline in University of California, San Diego Performance Based Skills Assessment-Brief International Version (UPSA-Bi) Assessment at Week 12 Baseline and 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.
Number of Participants With Response on Clinical Global Impression-Improvement (CGI-I) Scale at Week 12 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.
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scores at Week 12 Baseline and 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.
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 Up to Week 14 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.
Trial Locations
- Locations (34)
Atlanta Center for Medical Research
🇺🇸Atlanta, Georgia, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Hassman Research Institute
🇺🇸Berlin, New Jersey, United States
Artemis Institute for Clinical Research
🇺🇸San Diego, California, United States
Premier Clinical Research Institute, Inc.
🇺🇸Miami, Florida, United States
Pillar Clinical Research, LLC
🇺🇸Bentonville, Arkansas, United States
Collaborative Neuroscience Network, LLC
🇺🇸Garden Grove, California, United States
ProScience Research Group
🇺🇸Culver City, California, United States
Synergy San Diego
🇺🇸Lemon Grove, California, United States
Research Site
🇬🇧London, United Kingdom
Catalina Research Institute, LLC
🇺🇸Montclair, California, United States
Excell Research
🇺🇸Oceanside, California, United States
CNRI - San Diego, LLC
🇺🇸San Diego, California, United States
Yale University, Department of Psychiatry
🇺🇸New Haven, Connecticut, United States
Stedman Clinical Trials
🇺🇸Tampa, Florida, United States
Alexian Brothers Hospital Network
🇺🇸Hoffman Estates, Illinois, United States
Southern Illinois University, School of Medicine
🇺🇸Springfield, Illinois, United States
Cherry Health
🇺🇸Grand Rapids, Michigan, United States
St. Louis Clinical Trials, LC
🇺🇸Saint Louis, Missouri, United States
UB Department Psychiatry
🇺🇸Buffalo, New York, United States
Neurobehavioral Research, Inc.
🇺🇸Cedarhurst, New York, United States
Finger Lakes Clinical Research
🇺🇸Rochester, New York, United States
The Ohio State University Department of Psychiatry
🇺🇸Columbus, Ohio, United States
The University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Zentrum für klinische Forschung Dr. med. I. Schöll
🇩🇪Bad Homburg, Hessen, Germany
Clinic for Psychiatrie
🇩🇪Frankfurt, Hessen, Germany
Universitätsmedizin Göttingen, Klinik für Psychiatrie und Psychotherapie
🇩🇪Westerstede, Niedersachsen, Germany
Dpt of Psychiatry and Psychotherapy, University of Leipzig
🇩🇪Leipzig, Sachsen, Germany
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Unidad Neurociencias CS San Juan
🇪🇸Salamanca, Spain
Abraham Cowley Unit
🇬🇧Lyne, Surrey, United Kingdom
Hospital Universitario Marques Valdecilla
🇪🇸Santander, Cantabria, Spain
Oxford Health NHS Foundation Trust
🇬🇧Oxford, Oxfordshire, United Kingdom