Combining Iclepertin (BI 425809) With Computerized Cognitive Training in Patients With Schizophrenia: Baseline Data From an Ongoing Phase II Trial

Abstract Introduction There are currently no approved pharmacotherapies to treat cognitive impairment associated with schizophrenia (CIAS). Iclepertin (BI 425809) is a novel glycine transporter-1 inhibitor under development for treatment of CIAS. A previous study demonstrated pro-cognitive effects of iclepertin in patients with schizophrenia; however, concurrent cognitive stimulation could in theory enhance any pro-cognitive pharmacological effects on neuroplasticity. We present preliminary demographics and baseline data from a trial exploring the efficacy of iclepertin together with at-home computerized cognitive training (CCT). Methods This is an ongoing Phase II, double-blind, placebo-controlled, parallel-group trial in patients with schizophrenia on stable antipsychotic therapy across ~58 centers in 6 countries. Patients aged 18–50 years, compliant with CCT during the run-in period (completing ≥2 hours/week for 2 weeks), were randomized (1:1) to receive once-daily iclepertin 10 mg or placebo together with CCT for 12 weeks. Thereafter, minimum compliance for at-home CCT is 1 hour/week, with a target of ~30 hours across 3–5 sessions totaling 2.5 hours/week. Patients have been stratified to balance potential effects of age (18–40; 41–50 years). Primary endpoint is change from baseline (CfB) in neurocognitive composite T-score of the MATRICS Consensus Cognitive Battery (MCCB) at Week 12. Secondary endpoints include CfB in the Schizophrenia Cognition Rating Scale (SCoRS) total score, MCCB overall composite T-score, and Positive and Negative Syndrome Scale (PANSS) total scores. Novel exploratory endpoints include the Virtual Reality Functional Capacity Assessment Tool to assess daily functioning and the Balloon Effort Task to assess motivation in cognitive performance. Results Of the planned sample of 200 randomized patients, the overall treated population currently includes 183: 67% (n=122) are male; mean (standard deviation [SD]) age and time since first diagnosis are 38.2 (7.9) years and 13.5 (8.5) years. Overall, 49% (n=89) are White and 43% (n=79) are Black or African American; 80% (n=147) are from North America, 15% (n=28) from Europe, and 4% (n=8) from Australia/New Zealand. Mean (SD) baseline MCCB neurocognitive composite and overall T-scores (n=178) are 33.7 (11.9) and 32.5 (12.6). Mean (SD) baseline SCoRS total score (n=167) is 35.2 (8.7). Mean (SD) baseline PANSS total and negative symptom scale scores (n=183) are 64.7 (14.6) and 17.3 (5.4). Median (Q1, Q3) CCT compliance over the on-treatment period for patients who have completed or discontinued early is 2.00 (1.21, 2.51) hours/week. Conclusion This trial is, to our knowledge, the largest of its kind combining daily pharmacotherapy for CIAS with at-home CCT. It will indicate whether iclepertin together with concurrent cognitive stimulation provides enhanced cognitive benefit, and whether any improvements in neurocognition can translate into improved measures of daily functioning in patients. Funding Boehringer Ingelheim International GmbH (NCT03859973/1346-0038)