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

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 ≥3 months (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 ≥2 months prior to Baseline/Day 1,
including concomitant psychotropic treatments. Doses of background atypical
antipsychotics should be within the dose range listed in approved product labeling in
the United States (US).

- PANSS: No more than moderate-severe rating (score ≤5) on hallucinations, delusions,
and hostility; PANSS positive symptom items (P1, P3, P5, P6, P7); or unusual thought
content (G9); and no more than a moderate severity rating on positive formal thought
disorder (P2).

Key Exclusion Criteria:

- Participation in a CIAS trial within the previous 6 months.

- Participation in cognitive remediation therapy within 6 months prior to randomization.

- Screening MCCB Working Memory T-score ≥60 on either the Letter Number Span or the
Wechsler Memory Scale, Third Edition (WMS-III) Spatial Span task.

- 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.