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.

INTRODUCTION

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.

METHODS AND ANALYSIS: 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.

ETHICS AND DISSEMINATION: 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.

TRIAL REGISTRATION NUMBER: NCT06138210.