New Baseline Data on Iclepertin for Schizophrenia

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SPECIAL REPORT: ADVANCES IN PSYCHIATRY

The latest results from the phase 3 CONNEX-X study, which explores the potential of glycine transporter-1 inhibitor iclepertin (BI 425809) to address cognitive impairment associated with schizophrenia (CIAS), were shared in a poster during the 2024 American Psychiatric Association (APA) Annual Meeting in May.

Cognitive deficits are a hallmark of schizophrenia and significantly impact functional outcomes for patients, yet effective pharmacological interventions remain elusive, the study’s researchers explained. Building on promising results from earlier phase 2 trials that indicated iclepertin’s ability to enhance cognition in patients with schizophrenia, phase 3 trials are now underway. CONNEX-X (NCT05211947) is an extension trial aimed at gathering additional safety data regarding the long-term use of iclepertin in patients who have completed previous phase 3 trials.1

CONNEX-X represents a continued effort in this line of research. It is a multicenter, multinational, open-label, single-arm extension trial targeting individuals with cognitive impairment that is often observed in schizophrenia. The study includes patients who completed 26 weeks of treatment with either iclepertin 10 mg or matching placebo in 1 of 3 phase 3 CONNEX parent trials (NCT04846868, NCT04846881, NCT04860830).

The trial aims to enroll approximately 1400 patients who are clinically stable. These individuals will receive daily treatment with iclepertin 10 mg for 1 year, regardless of whether they previously received iclepertin or placebo in earlier studies.

Eligible participants must not exhibit suicidal behavior or suicidal ideation, must have not received a diagnosis of moderate/severe substance use disorder, and must have not received any DSM-5 diagnosis other than schizophrenia during the parent trial and up to the first visit of CONNEX-X. Patients with conditions preventing participation or who are experiencing significant decreases in hemoglobin levels are also excluded.

The primary objective of the CONNEX-X study is to monitor the occurrence of treatment-emergent adverse events. Secondary end points include changes from baseline in the Clinical Global Impressions-Severity scale and hemoglobin levels.

Moreover, efficacy end points encompass changes in cognitive and functional assessments, such as the MATRICS Consensus Cognitive Battery (MCCB) overall composite T-score, the Schizophrenia Cognition Rating Scale (SCoRS) total score, and the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) total times.

According to the latest analysis, 460 patients have been enrolled and randomly assigned from the parent trials, with a screening failure rate of 0% and an impressive rollover rate of approximately 80% as of August 30, 2023, the researchers reported. Baseline assessments conducted on a subset of 249 patients and analyzed on August 9, 2023, revealed mean scores for MCCB (29.5 [SD, 12.7] overall composite T-score), SCoRS (37.7 [SD, 9.8] interviewer total score), and VRFCAT (32.9 [SD, 20.8] adjusted total time).

“Patient enrollment rate from parent CONNEX trials to CONNEX-X has been stable to date,” the researchers reported in the poster. “This extension study will allow the examination of long-term safety and descriptive analyses of cognitive and functional end points of iclepertin in the treatment of CIAS, providing key evidence supporting its long-term use in chronic disorders such as schizophrenia."