Harvey Philip D, McDonald Sean, Fu Eric, Reuteman-Fowler Corey
University of Miami Miller School of Medicine, 1120 NW 14th Street, 33136, Miami, FL 33136, USA.
Boehringer Ingelheim (Canada) Ltd., 5180 South Service Rd, Burlington, Ontario L7L 5Y7, Canada.
Schizophr Res Cogn. 2024 Dec 14;40:100340. doi: 10.1016/j.scog.2024.100340. eCollection 2025 Jun.
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.
ClinicalTrials.gov identifier: NCT03859973.
尽管给患者带来了巨大负担，但目前尚无获批的药物疗法可治疗与精神分裂症相关的认知障碍症状（CIAS）。这项双盲、安慰剂对照、平行组II期试验评估了用艾考扑汀（BI 425809，一种甘氨酸转运体-1抑制剂）对居家计算机化认知训练（CCT）进行药物强化治疗的疗效和安全性。纳入了年龄在18至50岁、接受稳定抗精神病治疗且在导入期遵守CCT的精神分裂症患者。患者被随机（1:1）分为每日服用10毫克艾考扑汀或安慰剂，为期12周，所有患者均完成辅助性CCT。在第12周时，评估了MATRICS共识认知成套测验的神经认知综合T分数（主要终点）、精神分裂症认知评定量表访谈者总分以及阳性和阴性症状量表总分（次要终点）相对于基线的变化。还使用虚拟现实功能能力评估工具调整后的总时间T分数来评估表现。在200名随机分组的患者中，154名（77.0%）完成了试验。在疗效终点评估时，各治疗组之间未观察到差异。艾考扑汀10毫克 + CCT组有39名患者报告了不良事件（AE），安慰剂 + CCT组有57名患者报告了AE；大多数AE为轻至中度。据我们所知，该试验是将CIAS的每日药物治疗与居家CCT相结合的同类试验中规模最大的。尽管未证明疗效，但10毫克艾考扑汀的安全性与先前研究一致，且未发现新的风险。
ClinicalTrials.gov标识符：NCT03859973。
