A Phase 2b, Randomized, Double-Blind Vehicle Controlled, Dose Escalation Study Evaluating Clascoterone 0.1%, 0.5%, and 1% Topical Cream in Subjects With Facial Acne.

Androgens play a key role in acne pathogenesis in both males and females. Clascoterone (CB-03-01, Cortexolone 17α propionate) cream is a topical anti-androgen under investigation for the treatment of acne. The results from a phase 2b dose escalating study are discussed. Methods: Primary objective: to compare the safety and efficacy of topical creams containing clascoterone 0.1% (twice daily [BID]), 0.5% (BID), or 1% (daily [QD] or BID) versus vehicle (QD or BID) in male and female subjects ≥12 years with facial acne vulgaris. Efficacy was assessed by: Investigator’s Global Assessment (IGA)--the overall severity of acne using a five-point scale (from 0=clear to 4=severe); inflammatory and non-inflammatory acne lesion counts (ALC); and subject satisfaction with treatment--subjects assessed overall treatment satisfaction using a 4-point scale. Safety assessments: local and systemic adverse events (AEs), physical examination/vital signs, laboratory tests, local skin reactions (LSRs), and electrocardiograms (ECGs). Treatment success required a score of “clear” or “almost clear” (IGA score of 0 or 1) and a two or more-grade improvement from baseline. Results: 363 subjects (N=72, 0.1% BID; N=76, 0.5% BID; N=70, 1% QD; N=70, 1% BID; and N=75, vehicle QD or BID) enrolled. 304 subjects (83.7%) completed the study. Intention to Treat (ITT) population: 196/363 (54.0%) females; 167/363 46.0%) males; (257/363 (70.2%) were white; average age=19.7 years. Demographic and baseline characteristics were similar across all groups. Treatment success at week 12 were highest for the 1% BID (6/70, 8.6%) and 0.1% BID (6/72, 8.3%) groups versus vehicle (2/75, 2.7%). Absolute change in inflammatory (P=0.0431) and non-inflammatory (P=0.0303) lesions was statistically significant among the treatment groups. The median change from baseline at week 12 in inflammatory and non-inflammatory lesions was greatest in the 1% BID group -13.5 and -17.5, respectively. Similar results were observed for the secondary efficacy endpoints whereby the highest success rate and greatest reduction in lesion counts from baseline to week 12 occurred with 1% BID. 93/363 subjects (25.6%) reported ≥1 AEs; total number of AEs=123 with 2 probably/possibly related to treatment (N=1, 1% QD group). Subjects with ≥1AEs: 0.1% BID=25.0%, 0.5% BID=38.2%, 1% QD=22.9%, 1% BID=18.6%, and vehicle=22.7%. AEs were mostly mild in severity and similar across all groups. Most AEs (93/121 76.8%) resolved by the end of the study. Erythema was the most prevalent LSR; 36.8% had at least minimal erythema at some point during the study. Conclusions: All clascoterone cream concentrations were well tolerated with no clinically relevant safety issues noted. Clascoterone 1% BID treatment had the most favorable results and was selected as the best candidate for further clinical study and development. Two Phase 3 investigations of clascoterone topical cream, 1% for the treatment of moderate-to-severe acne vulgaris in individuals ≥9 years recently concluded. J Drugs Dermatol. 2019;18(6):570-575.