Phase 1/2 trials of human bone marrow–derived clonal mesenchymal stem cells for treatment of adults with moderate to severe atopic dermatitis - 13/07/24

Doi : 10.1016/j.jaci.2024.06.013

Hyun-Min Seo, MD, PhD ^a,^b, Bark-Lynn Lew, MD, PhD ^c, Yang Won Lee, MD, PhD ^d, Sang Wook Son, MD, PhD ^e, Chang Ook Park, MD, PhD ^f, Young Lip Park, MD, PhD ^g, Jin-Ok Baek, MD, PhD ^h, Min Kyung Shin, MD, PhD ^c, Dong Hyun Kim, MD, PhD ⁱ, Dong Hun Lee, MD, PhD ^j, Yong Hyun Jang, MD, PhD ^k, Hyun-Chang Ko, MD, PhD ^l, Chan-Ho Na, MD, PhD ^m, Young-Joon Seo, MD, PhD ⁿ, Dong-Sik Ham, PhD ^o, Dong-Jun Kim, BS ^o, Gwang Seong Choi, MD, PhD ^p,^⁎
^a Department of Dermatology, College of Medicine, Hanyang University Guri Hospital, Hanyang University, Seoul, Korea
^b Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea
^c Department of Dermatology, Kyung Hee University School of Medicine, Seoul, Korea
^d Department of Dermatology, Konkuk University School of Medicine, Seoul, Korea
^e Korea University College of Medicine, Seoul, Korea
^f Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea
^g Department of Dermatology, Soonchunhyang University College of Medicine, Bucheon, Korea
^h Department of Dermatology, Gachon University Gil Medical Center, Incheon, Korea
ⁱ CHA Bundang Medical Center, CHA University School of Medicine, Pangyo, Korea
^j Department of Dermatology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
^k Department of Dermatology, School of Medicine, Kyungpook National University, Daegu, Korea
^l Department of Dermatology, School of Medicine, Pusan National University, Yangsan, Korea
^m Department of Dermatology, College of Medicine, Chosun University, Gwangju, Korea
ⁿ Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea
^o SCM Lifescience Inc, Incheon, Korea
^p Department of Dermatology, School of Medicine, INHA University, Incheon, Korea

^∗Corresponding author: Gwang Seong Choi, MD, PhD, Department of Dermatology, INHA University Hospital, 27 Inhang-ro, Jung-gu, Incheon 22332, Republic of Korea.Department of DermatologyINHA University Hospital27 Inhang-roJung-guIncheon22332Republic of Korea

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Saturday 13 July 2024

graphical abstract

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Abstract

Background

Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses.

Objective

We investigated the safety and efficacy of allogenic human bone marrow–derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD).

Methods

The study included a phase 1 open-label trial followed by a phase 2 randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD.

Results

In phase 1, intravenous administration of hcMSCs at 2 doses (1 × 10⁶ and 5 × 10⁵ cells/kg) was safe and well tolerated in 20 subjects. Because there was no difference between the 2 dosage groups (P = .9), it was decided to administer low-dose hcMSCs only for phase 2. In phase 2, subjects receiving 3 weekly intravenous infusions of hcMSCs at 5 × 10⁵ cells/kg showed a higher proportion of an Eczema Area and Severity Index (EASI)-50 response at week 12 compared to the placebo group (P = .038). The differences between groups in the Dermatology Life Quality Index and pruritus numeric rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period.

Conclusions

The hcMSC treatment resulted in a significantly higher rate of EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSC treatment was acceptable. Further larger-scale studies are necessary to confirm these preliminary findings.

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Key words : Atopic dermatitis, clinical trial, mesenchymal stem cells, safety, treatment outcome

Abbreviations used : AD, AE, BSA, DLQI, EASI, hcMSC, IGA, MSC, TARC, TEAE, Treg