Safety, tolerability, and efficacy of a novel topical isotretinoin formulation for the treatment of X-linked or lamellar congenital ichthyosis: Results from a Phase 2a proof-of-concept study
Description
In this 2-part, phase 2a, double-blind study, patients ≥12 years with 2 comparable contralateral lesional areas with identical baseline Investigator Global Assessment (IGA) ≥3 scores were randomized 1:1 to PAT-001 0.1% or 0.2%. The treatment areas received PAT-001 (0.1% or 0.2%) or vehicle twice daily for 8 weeks in Part 1, and then both treatment areas received PAT-001 0.1% or 0.2% BID for 4 weeks in Part 2. Safety evaluations included adverse event (AE) monitoring and laboratory tests; efficacy outcomes included IGA scores and clinical signs. Among enrolled patients (PAT-001 0.1% [n = 10] and 0.2% [n = 9]), 14 experienced an AE. Most AEs were mild; 8 patients reported AEs that were possibly/probably/definitely treatment related; 7 discontinued treatment. There were no clinically significant changes from baseline in laboratory values and systemic isotretinoin/tretinoin concentrations remained at baseline levels. In Part 1, PAT-001 0.1% led to more ≥1 and ≥2 grade IGA reductions vs vehicle (100% vs 66.7%/66.7% vs 33.3%, respectively). PAT-001 0.2% resulted in more IGA reductions of 1 grade vs vehicle (50% vs 25%). Both PAT-001 concentrations improved scaling vs baseline at Days 57 and 84 (100%/75% vs 100%/80%, respectively) for continued active and vehicle/active treatment areas. In Part 2, IGA reductions in both treatment areas were observed in ≥80% of patients. Scaling in all patients for active vs vehicle treatment areas was clear, almost clear, or mild for 0.1% and 0.2% groups (100% vs 55.6%/100% vs 87.5%, respectively).