Efficacy and safety of iclepertin (BI 425809) with adjunctive computerized cognitive training in patients with schizophrenia

Despite significant patient burden, there are no approved pharmacotherapies to treat symptoms of cognitive impairment associated with schizophrenia (CIAS). This double-blind, placebo-controlled, parallel-group Phase II trial assessed the efficacy and safety of pharmacological augmentation of at-home computerized cognitive training (CCT) with iclepertin (BI 425809, a glycine transporter-1 inhibitor). Participants with schizophrenia (aged 18-50 years) on stable antipsychotic therapy, who were compliant with CCT during the run-in period, were enrolled. Patients were randomized (1:1) to once daily iclepertin 10 mg or placebo for 12 weeks, and all patients completed adjunctive CCT. At Week 12, the change from baseline in neurocognitive composite T-score of the MATRICS Consensus Cognitive Battery (primary endpoint), Schizophrenia Cognition Rating Scale interviewer total score, and Positive and Negative Syndrome Scale total score (secondary endpoints) were assessed. Performance was also assessed using Virtual Reality Functional Capacity Assessment Tool adjusted total time T-score. Of 200 randomized patients, 154 (77.0 %) completed the trial. At efficacy endpoint assessment, no differences were observed between treatment groups. Adverse events (AEs) were reported by 39 patients in the iclepertin 10 mg + CCT group and 57 patients in the placebo + CCT group; most AEs were mild to moderate. To our knowledge, this trial is the largest of its kind combining daily pharmacotherapy for CIAS with at-home CCT. Although efficacy was not demonstrated, the safety profile of iclepertin 10 mg was consistent with previous studies and no new risks were identified. Clinical trial registration: ClinicalTrials.gov identifier: NCT03859973.