Phase 1/2 trials of human bone marrow–derived clonal mesenchymal stem cells for treatment of adults with moderate to severe atopic dermatitis
Hyun‐Min Seo, Bark‐Lynn Lew, Yang Won Lee, Sang Wook Son, Chang Ook Park, Young Lip Park, Jin-Ok Baek, Min Kyung Shin, Dong Hyun Kim, Dong Hun Lee, Yong Hyun Jang, Hyun‐Chang Ko, Chan Ho Na, Young-Joon Seo, Dong‐Sik Ham, Dong-Jun Kim, Gwang Seong Choi
Abstract
BackgroundMesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses.ObjectiveWe investigated the safety and efficacy of allogenic human bone marrow–derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD).MethodsThe 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.ResultsIn 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.ConclusionsThe 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. Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses. We investigated the safety and efficacy of allogenic human bone marrow–derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD). 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. 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. 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.