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

A Phase 2, Randomized, Double-Blind, Multiple-Dose, Placebo-Controlled Study to Evaluate the Safety and Efficacy of BIIB104 in Subjects With Cognitive Impairment Associated With Schizophrenia (CIAS)

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment Associated With Schizophrenia
• Intervention / Treatment: Drug: BIIB104; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 195
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Hessen
    • Bad Homburg, Hessen, Germany, 61348
      • Zentrum für klinische Forschung Dr. med. I. Schöll
    • Frankfurt, Hessen, Germany, 60528
      • Clinic for Psychiatrie
  • Niedersachsen
    • Westerstede, Niedersachsen, Germany, 26655
      • Universitätsmedizin Göttingen, Klinik für Psychiatrie und Psychotherapie
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Dpt of Psychiatry and Psychotherapy, University of Leipzig
• Japan
  • Anan-shi, Japan
    • Research Site
  • Ichikawa-shi, Japan
    • Research Site
  • Kashihara-shi, Japan
    • Research Site
  • Kawasaki-shi, Japan
    • Research Site
  • Kita-gun, Japan
    • Research Site
  • Kodaira-shi, Japan
    • Research Site
  • Kumagaya-shi, Japan
    • Research Site
  • Takasaki-shi, Japan
    • Research Site
  • Yokosuka-shi, Japan
    • Research Site
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Madrid, Spain, 28040
    • Hospital Universitario 12 de octubre
  • Salamanca, Spain, 37005
    • Unidad Neurociencias CS San Juan
  • Sevilla, Spain, 41013
    • Research Site
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Research Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques Valdecilla
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Research Site
• United Kingdom
  • London, United Kingdom, SE5 8AZ
    • Research Site
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7JX
      • Oxford Health NHS Foundation Trust
  • Surrey
    • Lyne, Surrey, United Kingdom, KT16 0AE
      • Abraham Cowley Unit
• United States
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Pillar Clinical Research, LLC
  • California
    • Culver City, California, United States, 90230
      • Proscience Research Group
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, LLC
    • Lemon Grove, California, United States, 91945
      • Synergy San Diego
    • Long Beach, California, United States, 90807
      • Research Site
    • Montclair, California, United States, 91763
      • Catalina Research Institute, LLC
    • Oceanside, California, United States, 92056
      • Excell Research
    • Pico Rivera, California, United States, 90660
      • Research Site
    • San Diego, California, United States, 92123
      • Research Site
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • San Diego, California, United States, 92102
      • CNRI - San Diego, LLC
    • San Rafael, California, United States, 94901
      • Research Site
    • Torrance, California, United States, 90502
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University, Department of Psychiatry
  • Florida
    • Lauderhill, Florida, United States, 33319
      • Research Site
    • Miami, Florida, United States, 33122
      • Premier Clinical Research Institute, Inc.
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
    • Augusta, Georgia, United States, 30912
      • Augusta University
    • Decatur, Georgia, United States, 30030
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
    • Hoffman Estates, Illinois, United States, 60169
      • Alexian Brothers Hospital Network
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University, School of Medicine
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • Research Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Cherry Health
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Research Site
    • Saint Louis, Missouri, United States, 63141
      • St. Louis Clinical Trials, LC
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • New York
    • Buffalo, New York, United States, 104051
      • UB Department Psychiatry
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research, Inc.
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Department of Psychiatry
    • North Canton, Ohio, United States, 44720
      • Research Site
  • Texas
    • Richardson, Texas, United States, 75080
      • Research Site
    • San Antonio, Texas, United States, 78207
      • The University of Texas Health Science Center at San Antonio
  • Washington
    • Kirkland, Washington, United States, 98033
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Key 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).

Key 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIIB104 0.5 mg; Participants will receive 0.5 mg of BIIB104 twice a day, orally, for 12 weeks.	Drug: BIIB104; Administered as specified in the treatment arm; Other Names: PF-04958242
Experimental: BIIB104 0.15 mg; Participants will receive 0.15 mg of BIIB104 twice a day, orally, for 12 weeks.	Drug: BIIB104; Administered as specified in the treatment arm; Other Names: PF-04958242
Placebo Comparator: Matching Placebo; Participants will receive matching placebo twice a day, orally, for 12 weeks.	Other: Placebo; Administered as specified in the treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Week 12

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2018
• Primary Completion (Actual): March 23, 2022
• Study Completion (Actual): April 7, 2022

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: November 15, 2018
• First Posted (Actual): November 19, 2018

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Cognition Disorders; Schizophrenia; Cognitive Dysfunction
• Other Study ID Numbers: 263CS201; 2018-003825-27 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No