A Study to Assess Adverse Events, Change in Disease Activity, and How Oral Emraclidine Moves Through the Body in Adult Participants With Schizophrenia

An Adaptive Two-part Randomized, Double Blind, Placebo-controlled Phase 2 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of Emraclidine in Participants With Schizophrenia

Schizophrenia is a common and severe psychiatric illness characterized by extreme disturbances of cognition and thought, affecting language, perception and sense of self. This study will assess adverse events, change in disease activity, and how oral emraclidine moves through the body in adult participants with schizophrenia

Emraclidine is an investigational drug being developed for the treatment of schizophrenia. Participants are placed in one of two parts, Part A or Part B, where each group will receive a different treatment. Participants will receive either oral emraclidine or placebo. Approximately 268 participants will be enrolled across roughly 32 sites in the United States.

Participants in Part A will be assigned to one of multiple ascending doses of emraclidine or placebo administered orally for 14 days or up to 21 days. Participants in Part B will receive Emraclidine or placebo administered orally for up to 42 days. Participants will be followed for 30 days after the last dose of the study drug.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Inclusion Criteria:

• BMI within 18 to 40 kg/m2 (inclusive of both values), and body weight > 50 kg (110 lbs).
• (Part A only): Positive and Negative Syndrome Scale (PANSS) total score < 80 at Screening and at Baseline
• (Part B only): Participant experiencing an acute exacerbation of psychotic symptoms with onset less than 2 months prior to Screening
• (Part B only): Participant must have a PANSS total score from 80 to 120, inclusive, at Screening and at Baseline
• (Part B only): Participant MUST have a score of ≥ 4 (moderate or greater) for ≥ 2 of the following PANSS Positive Scale items at Screening and at Baseline
• (Part B only): Participant must have a Clinical Global Impression of Severity (CGIS) score ≥ 4 (at least moderately ill) at Screening and Baseline

Exclusion Criteria:

• Any primary DSM-5 disorder other than schizophrenia (current nicotine use disorder and caffeine use disorder are allowed) within 12 months before Screening.
• History of clozapine exposure.
• History of treatment resistance to schizophrenia medications, defined as failure to respond to 2 or more adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) within the last 12 months