Phase IIb randomized CONTROL study demonstrates a novel topical isotretinoin formulation, TMB-001, is safe and effective in participants with either recessive X-linked or autosomal recessive lamellar congenital ichthyosis.

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.

• 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)
• Copyright: Published by Oxford University Press on behalf of British Association of Dermatologists 2023.

Chemical References

• Isotretinoin
• Immunoglobulin A

Topics

• Humans
• Adult
• Ichthyosis, Lamellar (drug therapy, genetics)
• Isotretinoin (therapeutic use)
• Ichthyosiform Erythroderma, Congenital
• Ichthyosis
• Ichthyosis, X-Linked
• Immunoglobulin A