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.

The trial uses a two-stage design: a dose-escalation phase followed by a randomised, double-blind, placebo-controlled phase.

• Stage 1 is a dose-escalation study including three different dose levels with n=3 participants per dose level.
• Stage 2 is an expanded safety and preliminary efficacy phase with 20 patients randomised 1:1 to receive the highest safe dose identified in Stage 1 or placebo.
• The trial is multicentre, conducted across five hospitals in China between October 2023 and June 2026.
• The trial is registered as NCT06138210.

Eligible participants are patients with cortical ischaemic stroke enrolled within 1–7 days after symptom onset with a moderate-to-severe neurological deficit.

• Participants must have a diagnosis of cortical ischaemic stroke.
• Eligible patients must have a baseline National Institutes of Health Stroke Scale (NIHSS) score of 6–20.
• Enrolment must occur within 1–7 days after symptom onset.
• These criteria are designed to target a population with meaningful neurological impairment and a defined therapeutic window.

The primary safety endpoint is the incidence of serious adverse events within 90 days.

• The primary endpoint is defined as the incidence of serious adverse events within 90 days of treatment.
• This endpoint reflects the phase I/II focus on establishing clinical safety before broader efficacy testing.
• The trial was approved by the Ethics Committee of Xuanwu Hospital Capital Medical University (approval number [2023]161) and four additional hospital ethics committees.

Secondary efficacy endpoints encompass functional outcome, disability, neurological impairment, quality of life, and cognitive function at 90 days.

• Secondary 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 is also a secondary endpoint.
• Changes in NIHSS and Barthel Index scores at 90 days are included as secondary endpoints.
• EuroQol-5D-5L and Montreal Cognitive Assessment (MoCA) scores at 90 days are also secondary endpoints.

Preclinical studies have demonstrated the efficacy of stem cell-derived exosomes in animal models of ischaemic stroke, providing the rationale for this trial.

• The authors cite preclinical evidence supporting the use of stem cell-derived exosomes as a therapeutic strategy for ischaemic stroke.
• The investigational product consists of allogeneic human iPSC-derived exosomes.
• Cell-based therapies are described as 'a promising therapeutic strategy for enhancing neurological recovery after stroke.'

The trial protocol was developed in accordance with the Declaration of Helsinki and received ethics approval from five institutions.

• Ethics approval was obtained from 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 will be disseminated through peer-reviewed publication.
• The protocol was described as written 'according to the general ethical guidelines of the Declaration of Helsinki.'