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NCT03745820: TALLY

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

Completed Phase 2 Results posted Last updated 18 April 2023
What this trial tests

Phase 2 trial testing BIIB104 in Cognitive Impairment Associated With Schizophrenia in 195 participants. Completed in 7 April 2022.

Timeline
15 November 2018
Primary endpoint
23 March 2022
7 April 2022

Quick facts

Lead sponsorBiogen
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment195
Start date15 November 2018
Primary completion23 March 2022
Estimated completion7 April 2022
Sites60 locations across Japan, United Kingdom, Germany, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Biogen — full company profile →

Who can join

Adults 18 to 55, any sex, with Cognitive Impairment Associated With Schizophrenia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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 repo

GroupValue95% CI
Placebo1.17± 0.939
BIIB104 0.15 mg0.91± 0.936
BIIB104 0.5 mg0.84± 0.934
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Secondary · 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.

AEs
GroupValue95% CI
Placebo28
BIIB104 0.15 mg32
BIIB104 0.5 mg28
SAEs
GroupValue95% CI
Placebo1
BIIB104 0.15 mg1
BIIB104 0.5 mg2
Mean Total Score Assessed by Scale for the Assessment and Rating of Ataxia (SARA) Secondary · 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.

Baseline
GroupValue95% CI
Placebo0.5± 1.03
BIIB104 0.15 mg0.4± 1.15
BIIB104 0.5 mg0.3± 0.92
Week 2
GroupValue95% CI
Placebo0.4± 0.85
BIIB104 0.15 mg0.5± 1.10
BIIB104 0.5 mg0.3± 0.68
Week 6
GroupValue95% CI
Placebo0.4± 0.71
BIIB104 0.15 mg0.3± 0.90
BIIB104 0.5 mg0.2± 0.58
Week 12
GroupValue95% CI
Placebo0.4± 0.80
BIIB104 0.15 mg0.3± 0.82
BIIB104 0.5 mg0.2± 0.72
Week 14
GroupValue95% CI
Placebo0.4± 0.85
BIIB104 0.15 mg0.3± 0.91
BIIB104 0.5 mg0.2± 0.69
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 Secondary · 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),

GroupValue95% CI
Placebo3
BIIB104 0.15 mg4
BIIB104 0.5 mg0
Change From Baseline in University of California, San Diego Performance Based Skills Assessment-Brief International Version (UPSA-Bi) Assessment at Week 12 Secondary · 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.

GroupValue95% CI
Placebo2.07± 1.303
BIIB104 0.15 mg5.50± 1.292
BIIB104 0.5 mg5.49± 1.305
Change From Baseline in Schizophrenia Cognition Rating Scale (SCoRS) Assessment Score at Week 12 Secondary · 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 glob

GroupValue95% CI
Placebo-0.51± 0.146
BIIB104 0.15 mg-0.42± 0.148
BIIB104 0.5 mg-0.41± 0.145
Change From Baseline in MCCB Neurocognitive Composite Scores at Week 12 Secondary · 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

GroupValue95% CI
Placebo2.90± 0.733
BIIB104 0.15 mg1.80± 0.728
BIIB104 0.5 mg3.39± 0.727
Change From Baseline in MCCB Individual Domain Scores (Excluding Working Memory Domain) at Week 12 Secondary · 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 t

Verbal Learning: Change at Week 12
GroupValue95% CI
Placebo0.95± 0.951
BIIB104 0.15 mg1.41± 0.946
BIIB104 0.5 mg0.41± 0.950
Speed of Processing: Change at Week 12
GroupValue95% CI
Placebo4.42± 0.824
BIIB104 0.15 mg2.28± 0.819
BIIB104 0.5 mg3.99± 0.817
Attention/Vigilance: Change at Week 12
GroupValue95% CI
Placebo0.62± 0.852
BIIB104 0.15 mg0.53± 0.848
BIIB104 0.5 mg1.55± 0.848
Visual Learning: Change at Week 12
GroupValue95% CI
Placebo1.70± 1.131
BIIB104 0.15 mg0.19± 1.125
BIIB104 0.5 mg1.77± 1.125
Social Cognition: Change at Week 12
GroupValue95% CI
Placebo-0.13± 0.959
BIIB104 0.15 mg1.06± 0.953
BIIB104 0.5 mg0.95± 0.955
Reasoning and Problem Solving: Change at Week 12
GroupValue95% CI
Placebo2.81± 1.019
BIIB104 0.15 mg2.10± 1.1014
BIIB104 0.5 mg4.40± 1.011
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score, Positive Subscale, and Negative Subscale Scores at Week 12 Secondary · 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 subsca

Positive Symptoms Subscale: Change From Baseline at Week 12
GroupValue95% CI
Placebo-0.65± 0.431
BIIB104 0.15 mg-1.09± 0.430
BIIB104 0.5 mg-0.98± 0.429
Negative Symptoms Subscale: Change From Baseline at Week 12
GroupValue95% CI
Placebo-0.90± 0.461
BIIB104 0.15 mg-0.98± 0.461
BIIB104 0.5 mg-1.40± 0.460
Total Score: Change From Baseline at Week 12
GroupValue95% CI
Placebo-3.06± 1.429
BIIB104 0.15 mg-4.26± 1.421
BIIB104 0.5 mg-5.03± 1.427
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scores at Week 12 Secondary · 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.

GroupValue95% CI
Placebo-0.19± 0.091
BIIB104 0.15 mg-0.16± 0.091
BIIB104 0.5 mg-0.19± 0.091
Number of Participants With Response on Clinical Global Impression-Improvement (CGI-I) Scale at Week 12 Secondary · 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.

Very Much Improved
GroupValue95% CI
Placebo1
BIIB104 0.15 mg1
BIIB104 0.5 mg0
Much Improved
GroupValue95% CI
Placebo11
BIIB104 0.15 mg4
BIIB104 0.5 mg4
Minimally Improved
GroupValue95% CI
Placebo13
BIIB104 0.15 mg18
BIIB104 0.5 mg18
No Change
GroupValue95% CI
Placebo22
BIIB104 0.15 mg26
BIIB104 0.5 mg26
Minimally Worse
GroupValue95% CI
Placebo2
BIIB104 0.15 mg1
BIIB104 0.5 mg2
Much Worse
GroupValue95% CI
Placebo2
BIIB104 0.15 mg0
BIIB104 0.5 mg0
Very Much Worse
GroupValue95% CI
Placebo0
BIIB104 0.15 mg0
BIIB104 0.5 mg0

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug through end of the study (up to Week 14). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 1/63 (2%)
Deaths: 0/63
BIIB104 0.15 mg
Serious: 1/66 (2%)
Deaths: 0/66
BIIB104 0.5 mg
Serious: 2/66 (3%)
Deaths: 0/66

Serious adverse events (3 terms)

ReactionSystemPlaceboBIIB104 0.15 mgBIIB104 0.5 mg
AppendicitisInfections and infestations
SchizophreniaPsychiatric disorders
Psychiatric decompensationPsychiatric disorders
Other adverse events (2 terms — click to expand)

ReactionSystemPlaceboBIIB104 0.15 mgBIIB104 0.5 mg
HeadacheNervous system disorders
SchizophreniaPsychiatric disorders

Most-reported serious reactions: Appendicitis, Schizophrenia, Psychiatric decompensation.

Data from ClinicalTrials.gov NCT03745820 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics.
    Lobo MC, Whitehurst TS, Kaar SJ, Howes OD. · · 2022 · cited 74× · PMID 34838528 · DOI 10.1016/j.neubiorev.2021.11.032
  2. Positive AMPA receptor modulation in the treatment of neuropsychiatric disorders: A long and winding road.
    Kadriu B, Musazzi L, Johnston JN, Kalynchuk LE, et al · · 2021 · cited 37× · PMID 34358693 · DOI 10.1016/j.drudis.2021.07.027
  3. Understanding translational research in schizophrenia: A novel insight into animal models.
    Malik JA, Yaseen Z, Thotapalli L, Ahmed S, et al · · 2023 · cited 18× · PMID 36692676 · DOI 10.1007/s11033-023-08241-7
  4. Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia.
    Veselinović T, Neuner I. · · 2022 · cited 18× · PMID 35831706 · DOI 10.1007/s40263-022-00935-z
  5. ACNP 61<sup>st</sup> Annual Meeting: Poster Abstracts P271-P540.
    · 2022 · cited 7× · PMID 36456694 · DOI 10.1038/s41386-022-01485-0
  6. Progress in mechanistically novel treatments for schizophrenia.
    Neef J, Palacios DS. · · 2021 · cited 5× · PMID 34671731 · DOI 10.1039/d1md00096a
  7. Positive AMPA and Kainate Receptor Modulators and Their Therapeutic Potential in CNS Diseases: A Comprehensive Review.
    Vialko A, Chałupnik P, Szymańska E. · · 2025 · cited 1× · PMID 40650226 · DOI 10.3390/ijms26136450
  8. Amplification of the therapeutic potential of AMPA receptor potentiators from the nootropic era to today.
    Radin DP, Lippa A, Rana S, Fuller DD, et al · · 2025 · cited 1× · PMID 39894310 · DOI 10.1016/j.pbb.2025.173967

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