Efficacy and Safety of Topical Clascoterone Cream, 1%, for Treatment in Patients With Facial Acne: Two Phase 3 Randomized Clinical Trials

Abstract

Importance: Acne is a common, multifactorial skin condition, and treatments with novel mechanisms have been elusive.

Objective: To assess the safety and efficacy of clascoterone cream, 1%, a novel topical androgen receptor inhibitor, in 2 phase 3 randomized clinical trials (CB-03-01/25 and CB-03-01/26).

Design, setting, and participants: Two identical, multicenter, randomized, vehicle-controlled, double-blind, phase 3 studies conducted from November 2015 to April 2018 evaluated the efficacy and safety of use of clascoterone cream, 1%, in males and nonpregnant females 9 years and older with moderate or severe facial acne as scored on the Investigator's Global Assessment scale. Participants were enrolled if they had 30 to 75 inflammatory lesions and 30 to 100 noninflammatory lesions.

Interventions: Patients were randomized to treatment with clascoterone cream, 1%, or vehicle cream and applied approximately 1 g to the whole face twice daily for 12 weeks.

Main outcomes and measures: Treatment success was defined as an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear), and a 2-grade or greater improvement from baseline and absolute change from baseline in noninflammatory and inflammatory lesion counts at week 12. Safety measures included adverse event frequency and severity.

Results: A total of 1440 patients were randomzied in 2 studies. In CB-03-01/25, 353 participants were randomized to treatment with clascoterone cream, 1% (median [range] age, 18.0 [10-58] years; 221 [62.6%] female), and 355 participants were randomized to treatment with vehicle cream (median [range] age, 18.0 [9-50] years; 215 (60.6%) female); in CB-03-01/26, 369 participants were randomized to treatment with clascoterone cream, 1% (median [range] age, 18.0 [10-50] years; 243 [65.9%] female), and 363 participants were randomized to treatment with vehicle cream (median [range] age, 18.0 [range, 11-42] years; 221 [60.9%] female). At week 12, treatment success rates in CB-03-01/25 and CB-03-01/26 with clascoterone cream, 1%, were 18.4% (point estimate, 2.3; 95% CI, 1.4-3.8; P < .001) and 20.3% (point estimate, 3.7; 95% CI, 2.2-6.3; P < .001) vs 9.0% and 6.5% with vehicle, respectively. At week 12, in both CB-03-01/25 and CB-03-01/26, treatment with clascoterone cream, 1%, resulted in a significant reduction in absolute noninflammatory lesions from baseline to -19.4 (point estimate difference, -6.4; 95% CI, -10.3 to -2.6; P < .001) and -19.4 (point estimate difference, -8.6; 95% CI, -12.3 to -4.9; P < .001) vs -13.0 and -10.8 with vehicle, respectively, as well as a reduction in inflammatory lesions from baseline to -19.3 (point estimate difference, -3.8; 95% CI, -6.4 to -1.3; P < .001) and -20.0 (point estimate difference, -7.4; 95% CI, -9.8 to -5.1; P < .001) vs -15.5 and -12.6 with vehicle, respectively. Adverse events rates were low and mostly mild; the predominant local skin reaction was trace or mild erythema.

Conclusions and relevance: Use of clascoterone cream, 1%, for acne treatment appears to demonstrate favorable efficacy and safety with low adverse event rates.

Trial registration: ClinicalTrials.gov Identifiers: NCT02608450 and NCT02608476.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Hebert, Thiboutot, and Stein Gold were study investigators and are compensated (ie, honoraria, personal fees) advisors to Cassiopea. Dr Hebert is an employee of the McGovern Medical School of The University of Texas Health Science Center in Houston, which received compensation from Cassiopea SpA for study participation; she also received honorarium for serving on the Cassiopea advisory board. Dr Stein Gold is an employee of the Henry Ford Health System in Detroit, Michigan, which received compensation from Cassiopea SpA for study participation; she has also received personal fees for advisory, speaking, consulting, research, and/or other ties with Almirall, Foamix, Galderma Laboratories, Novartis, Sol-Gel, and Sun Pharmaceuticals. Dr Thiboutot is an employee of the College of Medicine at The Pennsylvania State University in Hershey, which received compensation from Cassiopea SpA for study participation; she has also received grants and honoraria from Botanix, Galderma Laboratories, and Novartis. Dr Cartwright is employed as the senior director of medical affairs for Cassiopea Inc and received personal fees as a consultant to Cassiopea SpA; receives personal fees as an adjunct faculty member at the University of Arizona; holds stock options in Cassiopea SpA; and previously was a contracted employee of Anacor-Pfizer and consultant to Menlo Therapeutics, NICO Corporation, and Abbott Nutrition. Dr Gerloni is an employee and officer of Bellatrix Pharmaceuticals, a subsidiary of Cosmo Pharmaceuticals, the parent company of Cassiopea SpA and Cassiopea Inc, and is a research consultant to Cassiopea SpA. Mr Fragasso is employed as the clinical project manager for Cassiopea SpA and holds stock options in the company. Dr Mazzetti is employed as the chief medical officer for Cassiopea SpA and holds stock options in the company, is a board member of Cassiopea SpA, and has served as the chief medical officer for Cosmo Pharmaceuticals.

Figures

Figure 1.. Proposed Mechanism of Action of Clascoterone

A, Acne is characterized by epithelial hyperkeratinization, excessive sebum production, Cutibacterium acnes colonization of the pilosebaceous unit, and inflammation. B, Within the sebaceous gland, sebocytes convert precursor molecules into androgens including dihydrotestosterone (DHT)., C, Within sebocytes, DHT binds to androgen receptors in the cytosol. On binding, the DHT-androgen receptor complex dimerizes and translocates to the nucleus. There, it influences transcription of genes involved in acne pathogenesis, including sebum and inflammatory cytokine production., D, Clascoterone, applied topically to the skin, binds to the androgen receptor with high affinity at the site of application, competing with DHT.,, Results from in vitro studies suggest it thereby limits the effect of DHT on transcription of genes that modulate sebum production and inflammation.,

Figure 2.. CONSORT Diagrams

Figure 3.. Improvement of Acne in Patients Treated With Clascoterone Topical Cream, 1%, Twice Daily for 12 Weeks

Representative photographs of 3 patients, both male and female, at baseline and week 12.