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

TL;DR

This study examines the long-term safety of iclepertin, a drug for cognitive impairment in schizophrenia, in patients who previously participated in Phase III trials.

Contribution

The study provides preliminary data on the long-term safety and cognitive outcomes of iclepertin in schizophrenia patients.

Findings

460 patients have been enrolled in the CONNEX-X extension study with a 0% screening failure rate.

The study will explore long-term safety and cognitive/functional endpoints of iclepertin.

Enrollment rates from the parent trials to the extension study are stable.

Abstract

Cognitive impairment associated with schizophrenia (CIAS) is an important unmet need as there are no effective treatments available. Iclepertin (BI 425809), a glycine transporter-1 inhibitor, has been shown to improve CIAS in Phase II trials, and Phase III trials are underway.

The ongoing CONNEX-X extension study aims to collect additional safety data relating to iclepertin treatment in patients with CIAS.

CONNEX-X (NCT05211947/1346-0014) is a multinational, multicentre, open-label, single-arm extension study in patients with CIAS who completed 26 weeks of treatment (iclepertin 10 mg or placebo) in one of 3 Phase III CONNEX parent trials (NCT04846868/1346-0011, NCT04846881/1346-0012, NCT04860830/1346-0013). An estimated 1400 clinically stable outpatients will be treated (iclepertin 10 mg daily) for 1 year, irrespective of previous treatment (iclepertin/placebo). Patients are excluded if any of the following circumstances occur during the parent study and up to Visit 1 of CONNEX-X: suicidal behaviour or ideation (type 5 on the Columbia-Suicide Severity Rating Scale), diagnosis with moderate/severe substance use disorder, diagnosis other than schizophrenia (according to Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition), development of any condition preventing participation, a haemoglobin level decrease (>25% or <100g/L from baseline in parent trial) or haemoglobinopathies. The primary endpoint is the occurrence of treatment-emergent adverse events. The secondary endpoints include change from baseline (CfB) in Clinical Global Impressions-Severity (CGI-S) and CfB in haemoglobin. Further efficacy endpoints include CfB in MATRICS Consensus Cognitive Battery (MCCB) overall composite T-score, CfB in Schizophrenia Cognition Rating Scale total score and CfB in Virtual Reality Functional Capacity Assessment Tool (VRFCAT) total times.

Currently, 460 patients have been enrolled and randomised from the parent trials with 0% screening failures (-80% roll-over rate, 30 August 2023). Current study status, including recruitment, screening failures and data collection experiences, are presented.

Patient enrolment rates from the CONNEX trials to the CONNEX-X open-label extension study are stable. CONNEX-X will allow the exploration of long-term safety, as well as descriptive analyses of cognitive and functional endpoints of iclepertin in the treatment of CIAS.

Boehringer Ingelheim

C. Reuteman-Fowler Employee of: Boehringer Ingelheim Pharmaceuticals, Inc., Z. Blahova Employee of: Boehringer Ingelheim RCV GmbH & Co. KG, S. Marder Consultant of: Boehringer Ingelheim Pharma GmbH, Merck, Biogen and Sunovion, S. Ikezawa Consultant of: Boehringer Ingelheim Pharma GmbH, Lundbeck, Takeda Pharma, Sumitomo Dainippon Pharma, Employee of: International University of Health and Welfare, Mita Hospital, Tokyo, Japan, P. Falkai Consultant of: Boehringer Ingelheim Pharma GmbH, Boehringer Ingelheim Pharma advisory board