Abstract | BACKGROUND: In two severe congenital ichthyosis subtypes, autosomal recessive lamellar ichthyosis (ARCI-LI) and X-linked recessive ichthyosis (XLRI), cutaneous manifestations include widespread scaling. Approved topical treatment options are limited to emollients and keratolytics. AIM: This analysis from the randomized phase IIb CONTROL study assessed whether the efficacy and safety of TMB-001, a novel topical isotretinoin ointment formulation, differed between ARCI-LI and XLRI subtypes. METHODS: Participants ≥ 9 years with genetically confirmed XLRI or ARCI-LI and ≥ 2 (of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with ≥ 3 scaling score were randomized 1 : 1 : 1 to TMB-001 0.05%/TMB-001 0.1%/vehicle, twice daily for 12 weeks. The proportion of participants with ≥ 50% reduction vs. baseline in VIIS scaling (VIIS 50; primary endpoint) and ≥ 2-grade reduction in Investigator's Global Assessment ( IGA)-scaling score vs. baseline (key secondary endpoint) were evaluated. Adverse events (AEs) were monitored. RESULTS: Among enrolled participants (TMB-001 0.05%, n = 11; 0.1%, n = 10; and vehicle, n = 12), 52% had ARCI-LI and 48% XLRI subtypes. Mean age was 33.6 and 35.4 years for participants with ARCI-LI and XLRI, respectively. Overall, 33%, 50% and 17% of participants with ARCI-LI and 100%, 33% and 75% of participants with XLRI achieved VIIS 50 in the TMB-001 0.05%, TMB-001 0.1% and vehicle groups, respectively (nominal P = 0.24 for 0.05% vs. vehicle, intent-to-treat population). Improvement of ≥ 2-grade IGA score was observed in 33%, 50% and 0% of participants with ARCI-LI and 83%, 33% and 25% of participants with XLRI in the TMB-001 0.05%, TMB-001 0.1% and vehicle groups, respectively (nominal P = 0.03 for 0.05% vs. vehicle, intention-to-treat population). Most AEs were application-site reactions. CONCLUSION: Regardless of congenital ichthyosis subtype, TMB-001 demonstrated greater proportions of participants achieving VIIS 50 and ≥ 2-grade IGA improvement vs. vehicle.
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Authors | Dedee F Murrell, Joyce M C Teng, Scott Guenthner, Kalyani Marathe, Steven Kempers, Kimmie Eads, Leslie Castelo-Soccio, Alan M Mendelsohn, Jessica Raiz, Christopher G Bunick |
Journal | Clinical and experimental dermatology
(Clin Exp Dermatol)
Vol. 48
Issue 6
Pg. 623-630
(Jun 05 2023)
ISSN: 1365-2230 [Electronic] England |
PMID | 36794376
(Publication Type: Randomized Controlled Trial, Journal Article)
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Copyright | Published by Oxford University Press on behalf of British Association of Dermatologists 2023. |
Chemical References |
- Isotretinoin
- Immunoglobulin A
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Topics |
- Humans
- Adult
- Ichthyosis, Lamellar
(drug therapy, genetics)
- Isotretinoin
(therapeutic use)
- Ichthyosiform Erythroderma, Congenital
- Ichthyosis
- Ichthyosis, X-Linked
- Immunoglobulin A
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