Efficacy and Safety of 1% Clascoterone Cream in Patients Aged > 12 Years With Acne Vulgaris.

BACKGROUND: Two randomized phase 3 studies evaluated efficacy and safety of 1% clascoterone cream, a topical androgen receptor inhibitor, in patients aged ≥9 years with moderate-to-severe facial acne vulgaris after 12 weeks of treatment. OBJECTIVES: To present a pooled data analysis of the efficacy and safety of 1% clascoterone cream after 12 weeks of treatment in patients aged ≥12 years from the 2 phase 3 trials. METHODS: Patients were randomized 1:1 to twice-daily treatment of the whole face with clascoterone or vehicle. Primary efficacy outcomes were proportion of patients achieving treatment success (Investigator Global Assessment score of "clear" [0] or "almost clear" [1] with ≥2-point reduction from baseline) and absolute change from baseline (CFB) in noninflammatory lesion count and inflammatory lesion count; secondary efficacy outcomes included absolute CFB in total lesion count at week 12. Safety was assessed from treatment-emergent adverse events and local skin reactions. RESULTS: 709/712 patients age ≥12 years were treated with clascoterone/vehicle. After 12 weeks, clascoterone was efficacious compared with vehicle, based on proportion of patients achieving treatment success (19.9% vs 7.7%) and CFB in noninflammatory lesion count (-20.8 vs -11.9), inflammatory lesion count (-19.7 vs -14.0), and total lesion count (-40.0 vs -26.1; all P<0.0001). Frequencies of local skin reactions were low and similar between treatment arms, with no new safety signals. CONCLUSIONS: Clascoterone is efficacious, with a favorable safety profile and low rates of local skin reactions in patients ≥12 years of age with facial acne vulgaris. (Clinicaltrials.gov NCT02608450 and NCT02608476) J Drugs Dermatol. 2023;22(2): doi:10.36849/JDD.7000.

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

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.

Open-label, long-term extension study to evaluate the safety of clascoterone (CB-03-01) cream, 1% twice daily, in patients with acne vulgaris.

BACKGROUND: Androgens foster acnegenic pathways. OBJECTIVE: To assess the long-term safety of an androgen receptor inhibitor, clascoterone cream, 1%, in patients who participated in phase 3 studies. METHODS: Clascoterone cream was applied twice daily for up to 9 months to the face or trunk, or both. Treatment-emergent adverse events (TEAEs) and local skin reactions were evaluated at months 1, 3, 6, and 9, and at any unscheduled visit(s). The statistical analysis was performed using SAS Windows 9.3 software (SAS Institute Inc, Cary, NC). RESULTS: The study screened and enrolled 609 individuals (n = 317 clascoterone, n = 292 vehicle from original studies), and 347 completed the study (n = 179 clascoterone, n = 168 vehicle). Overall, 110 patients (18.1%) experienced 191 TEAEs. The most frequently reported TEAE was nasopharyngitis (n = 20). A total of 19 test article-related TEAEs occurred in 14 patients; of these, 9 experienced 9 TEAEs leading to discontinuation. There were 7 serious TEAEs in 6 individuals, but none were treatment related. One serious TEAE led to study discontinuation. Overall, treatment-emergent local skin reactions occurred in 18.1% (110 of 607). The most frequent local skin reactions on the face and trunk were erythema, scaling/dryness, and pruritus, and most were trace/minimal or mild in severity. LIMITATIONS: Long-term efficacy was not a primary end point. CONCLUSION: A low frequency of TEAEs over 9 months of clascoterone treatment was observed.