Clinical safety and preliminary efficacy of allogeneic human induced pluripotent stem cell-derived exosomes in patients with acute ischaemic stroke: protocol of a phase I/II clinical trial in China.

Abstract

Cell-based therapies represent a promising therapeutic strategy for enhancing neurological recovery after stroke. Preclinical studies have demonstrated the efficacy of stem cell-derived exosomes in animal models of ischaemic stroke. We aim to evaluate the safety and preliminary efficacy of allogeneic human induced pluripotent stem cell (iPSC)-derived exosomes in patients with acute ischaemic stroke. This is a multicentre, prospective, phase I/II clinical trial conducted in China between October 2023 and June 2026. Eligible participants will be patients with a diagnosis of cortical ischaemic stroke, a baseline National Institutes of Health Stroke Scale (NIHSS) score of 6-20 and enrolment within 1-7 days after symptom onset. Stage 1 is a dose-escalation study including three different dose levels (n=3 per dose). Stage 2 is an expanded safety and preliminary efficacy phase with a randomised, double-blind, placebo-controlled design. In Stage 2, 20 patients will be randomised 1:1 to receive the highest safe dose identified in Stage 1 or placebo. The primary endpoint is the incidence of serious adverse events within 90 days. Secondary efficacy endpoints include the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-2 at 90 days, ordinal mRS distribution at 90 days and changes in NIHSS and Barthel Index scores at 90 days, as well as EuroQol-5D-5L and Montreal Cognitive Assessment (MoCA) scores at 90 days. This protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Xuanwu Hospital Capital Medical University (approval number [2023]161), the Third People's Hospital of Liaocheng, the First People's Hospital of Chenzhou, Zibo Municipal Hospital and Mianyang Central Hospital. Results of this study will be disseminated through peer-reviewed publication. NCT06138210.