The CONTROL study: A randomized, double-blind vehicle-controlled Phase 2b study of novel topical isotretinoin formulation demonstrates improvement in recessive X-linked and autosomal recessive lamellar congenital ichthyosis
Description
Congenital ichthyosis (CI) includes keratinizing disorders. This Phase 2b study assessed efficacy and safety of TMB-001, a novel topical isotretinoin ointment formulation, in patients with recessive X-linked (XLRI) and autosomal recessive lamellar ichthyosis (ARCI-LI). Participants ≥9 years, clinical CI diagnosis of 10%–90% of total body surface area affected, and ≥2 (out of 4) assessment areas with Visual Index for Ichthyosis Severity (VIIS) score ≥3 were randomized (1:1:1) to TMB-001 0.05%:TMB-001 0.1%:vehicle treatment twice daily for 12 weeks. Key efficacy endpoints were ≥50% VIIS scaling reduction (VIIS-50) vs baseline and ≥2-grade Investigator Global Assessment (IGA) score reduction vs baseline. Adverse events (AEs) and local skin reactions (LSRs) were evaluated. Among enrolled participants (TMB-001 0.05% [n=11], 0.1% [n=10], and vehicle [n=12]), 52% had ARCI-LI and 48% had XLRI. Overall, 64%/40%/33% of participants receiving TMB-001 0.05%/0.1%/vehicle achieved VIIS-50, respectively. Improvement of ≥2-grade IGA score was observed in 55%/40%/8% of participants receiving TMB-001 0.05%/0.1%/vehicle, respectively. Most AEs and LSRs were mild or moderate in severity. A greater proportion of participants achieved VIIS-50 and ≥2-grade IGA improvement following TMB-001 0.05% treatment vs vehicle.