REGENECYTE cord blood cell therapy in post-COVID syndrome: a phase IIa randomized, placebo-controlled trial

Post-COVID syndrome affects a substantial proportion of individuals worldwide and imposes significant healthcare and economic burdens. Fatigue is one of the most common and debilitating symptoms in those with severe symptoms related to post-COVID fatigue syndrome, yet there remains a lack of targeted therapies, effective or approved treatments to address it. This study aimed to evaluate the safety, tolerability, and efficacy of repeated doses of REGENECYTE, an allogeneic hematopoietic progenitor cell (HPC) therapy derived from cord blood, in patients with post-COVID syndrome.

In this randomized, single-blind, placebo-controlled, phase IIa trial, we evaluated repeated intravenous infusions of REGENECYTE from different donors (without HLA matching) in patients with post-COVID syndrome in the USA. Eligible adults aged 18-65 years had persistent post-COVID symptoms between 6 and 18 months and tested negative for SARS-CoV-2 within 7 days before enrollment. Participants were randomized into a 2:1 ratio to receive either REGENECYTE or placebo. Three infusions were administered over 6 weeks, 3 weeks apart, followed by a 20-week follow-up. Each dose of REGENECYTE contains at least 1 × 10⁷ total nucleated cells (TNC)/kg, with a cumulative dose of at least 3 × 10⁷ TNC/kg per patient. The primary endpoint was safety, assessed using the Common Terminology Criteria for Adverse Events by National Cancer Institute (NCI CTCAE) v5.0. The key secondary endpoint focused on changes in fatigue using the Chalder Fatigue Questionnaire (CFQ-11), while exploratory endpoints evaluated frailty, quality of life, and cognition using validated instruments. This trial was registered with ClinicalTrials.gov, NCT05682560.

Between May 4 and Dec 26, 2023, 30 eligible patients were enrolled and completed the study. The mean age was 41.9 years; 70% were female. The average duration of post-COVID symptoms was 306 days. Only 2 patients (10%) in the REGENECYTE group experienced mild treatment-emergent adverse events (TEAEs), indicating good tolerability. Notably, REGENECYTE significantly and sustainably improved fatigue symptoms, as measured by CFQ-11 Bimodal and Likert scores, compared to placebo (p < 0.01). Improvements were observed as early as week 6 and persisted through the 20-week follow-up. The most pronounced benefit was seen in the physical fatigue domain. REGENECYTE also improved quality of life in domains such as usual activities and mental wellbeing. There were no significant changes in frailty or cognitive scores.

REGENECYTE was well tolerated and safe when administered as repeat infusions from unmatched cord blood donors. It produced a meaningful and durable reduction in fatigue symptoms, the most burdensome feature of post-COVID syndrome-highlighting its potential as a novel therapeutic strategy. These findings support further clinical development of cord blood-based therapies targeting fatigue in post-COVID and potentially other fatigue-related conditions.

StemCyte International, Ltd.