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

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. This randomized phase IIb CONTROL study analysis assessed the efficacy and safety of TMB-001, a novel topical isotretinoin ointment, by congenital ichthyosis subtype (autosomal recessive lamellar ichthyosis and X-linked recessive ichthyosis). Participants received TMB-001 0.05% (n = 11); 0.1% (n = 10); and vehicle (n = 12) and the primary endpoint was assessed with the Visual Index for Ichthyosis Severity scale. Regardless of congenital ichthyosis subtype, there was improvement in congenital ichthyosis symptoms with TMB-001 vs. vehicle.

Automated summary

This analysis evaluated the efficacy and safety of a novel topical isotretinoin ointment, TMB-001, in different subtypes of congenital ichthyosis. The results showed that regardless of the subtype, TMB-001 demonstrated greater improvement in symptoms compared to vehicle.