Promising Phase 1/2 Trial Results of Stem Cells for AD

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A recent study explored the efficacy and safety of human bone marrow-derived clonal mesenchymal stem cells (hcMSCs) to treat patients with moderate to severe atopic dermatitis (AD). Researchers found that hcMSCs treatment resulted in a “significantly higher rate” of achieving Eczema Area and Severity Index (EASI)50 at 12 weeks compared to the control group, leading them to suggest further larger-scale studies.¹

Background

In previous studies investigating the potential of hcMSCs for immunomodulation in various conditions, hcMSCs were proven to be safe and reduce inflammatory markers in patients with acute pancreatitis.² Similarly, in a preclinical mouse AD model, researchers reported that key biomarkers responsible for regulating immune inflammatory responses were regulated by hcMSCs.³ This study represents the first human trial assessing the safety, tolerability, and efficacy of hcMSCs inpatients with moderate to severe AD.

Methods

The study (NCT04179760) involved 2 phases. Phase 1 was a randomized, open-label trial across 6 Korean sites with 20 patients. They received either high-dose (1x10^6 cells/kg) or low-dose (5x10^5 cells/kg) hcMSCs via 3 IV infusions every 2 weeks. Safety was closely monitored, and if no serious adverse effects were seen, more patients were enrolled. Phase 2 of the study expanded to 72 patients with moderate to severe AD from 15 sites, using only the low-dose hcMSCs in a double-blind, placebo-controlled setup. Infusions were given over 3 weeks, with follow-ups over 24 weeks.

Rescue therapy was allowed for patients experiencing intolerable AD symptoms despite treatment, starting with topical medications and progressing to stronger treatments under medical supervision, but not including oral corticosteroids.

Results

Researchers stated the primary goal in phase 1 was to assess EASI50 response rates, which were 70% and 67% for high-dose and low-dose hcMSCs, respectively, with no significant difference between groups. In phase 2, researchers reported that patients receiving low-dosehcMSCs (5×10^5 cells/kg) showed a higher EASI-50 response rate (58%) compared to placebo (32%) at week 12, which they stated was statistically significant.

Secondary endpoints in phase 2 included higher rates of EASI90 responses (24% vs. 6%), quicker achievement of EASI75, and improvements in Investigator Global Assessment(IGA) scores and affected Body Surface Area (BSA) with hcMSCs compared to placebo. The study authors stated changes in pruritus and quality of life scores did not significantly differ between groups, and there were no significant differences in serum biomarker levels between groups.

Safety profiles showed that adverse events (AEs) were mild to moderate, with infections being the most common. In phase 1, researchers reported that AEs affected 10% (arm 1) and 30% (arm 2) of patients. In phase 2, AEsreportedly affected 28% (hcMSCsgroup) and 22% (placebo group), with most resolving by the study's end.

Conclusion

Overall, the study demonstrated that low dosehcMSCs were effective in improving AD symptoms and had a manageable safety profile compared to placebo, supporting researcher’s hypothesis in their potential as a treatment option for moderate to severe AD. The study suggested that a larger-scale, more comprehensive evaluation is necessary to determine the long-term sustainability of the observed effects. 

References

1. Seo HM, Lew BL, Lee YW, et al. Phase I/II trials of human bone marrow-derived clonal mesenchymal stem cells for treatment of adults with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. Published online June 27, 2024. doi:10.1016/j.jaci.2024.06.013
2. Shin IS, Park CH, Moon JH, et al. Human bone marrow-derived clonal mesenchymal stem cells decrease the initial C-reactive protein level in patients withmoderately severe to severe acute pancreatitis. Gastroenterology. 2023;164(7):1317-1320.e2. doi:10.1053/j.gastro.2023.02.009
3. Na K, Yoo HS, Zhang YX, et al. Bone marrow-derived clonal mesenchymal stem cells inhibit ovalbumin-induced atopic dermatitis. Cell Death Dis. 2014;5(7):e1345. Published 2014 Jul 17. doi:10.1038/cddis.2014.299