Preliminary data from the CONNEX-X extension trial examining the long-term safety of iclepertin (BI 425809) in patients with schizophrenia who completed Phase III CONNEX trials

Abstract: Introduction: Iclepertin (BI 425809), a glycine transporter-1 inhibitor, has improved cognitive impairment associated with schizophrenia (CIAS) in Phase II trials, with Phase III trials underway. The CONNEX-X extension study aims to examine the long-term safety of iclepertin to treat CIAS. Methods: CONNEX-X is a multinational, multicenter, open-label, single-arm extension study in patients with CIAS who completed treatment (26 weeks, iclepertin 10mg or placebo) in one of 3 Phase III CONNEX parent trials. Approximately 1400 clinically stable outpatients will be treated (1 year, iclepertin 10mg daily). Patients are excluded if any of the following occurred up to Visit 1 of CONNEX-X: suicidal behavior/ideation, diagnosis with moderate/severe substance use disorder, diagnosis other than schizophrenia, development of any condition preventing participation, hemoglobin level decrease (>25% or < 100g/L from CONNEX baseline) or hemoglobinopathies. Primary endpoint: occurrence of treatment-emergent adverse events. Secondary endpoints include: change from baseline (CfB) in Clinical Global Impressions-Severity and in hemoglobin. Further efficacy endpoints include: CfB in MATRICS Consensus Cognitive Battery overall composite T-score, in Schizophrenia Cognition Rating Scale total score, and in Virtual Reality Functional Capacity Assessment Tool total times. Results: 460 patients have been enrolled and randomized from CONNEX with 0% screening failures (~80% roll-over rate, August 30, 2023). Current study status, including recruitment, screening failures and data collection experiences, are presented. Conclusion: Patient enrolment rates from CONNEX to CONNEX-X are stable. CONNEX-X will explore long-term safety and descriptive analyses of cognitive and functional endpoints of iclepertin in CIAS treatment. This study is funded by Boehringer Ingelheim (NCT05211947).Short Description: Iclepertin (BI 425809) is a novel glycine transporter-1 inhibitor for the treatment of cognitive impairment associated with schizophrenia that has shown proof-of-clinical-concept and tolerability in a Phase II clinical trial. This abstract describes the CONNEX-X trial; an ongoing, multinational, multicenter, open-label, single-arm extension study to assess the long-term safety of iclepertin to treat patients with CIAS.Name of Sponsoring Organization(s): Boehringer Ingelheim.