Clascoterone is a topical androgen receptor inhibitor under investigation for the treatment of acne. Clascoterone is hydrolyzed by the skin and metabolized to cortexolone 21-propionate and cortexolone. Both metabolites exhibit minimal anti-androgen activity and weak glucocorticoid properties [1,2]. Cortexolone is the final compound which has an established safety profile [1,2]. This agent targets androgen receptors in sebocytes and hair papilla cells within the skin’s pilosebaceous unit, intervenes at multiple and different points in acne pathogenesis, and inhibits dihydrotestosterone-stimulated signaling downstream of the androgen receptors.

• The primary purpose of the study was to assess the efficacy of clascoterone topical 1% cream for the treatment of facial acne vulgaris in adult and pediatric populations.
• The study assessed percent reduction in inflammatory and non-inflammatory facial lesions over a 12-week period.

Type of Study

• Phase 3.
• Randomized.
• Double-blind.
• Vehicle controlled.
• Multicenter.
• Two identical studies (25 & 26) at 112 sites.

Primary Purpose

• The primary purpose of the study was to assess the efficacy of clascoterone topical 1% cream for the treatment of facial acne vulgaris in adult and pediatric populations.
• The study assessed percent reduction in inflammatory and non-inflammatory facial lesions over a 12-week period.

Patient Populations

• Total number of enrollees : 1,440 patients.
• Age : ≥9 years.
• Intent-to-treat population.
• Inclusion criteria :
  • 30-75 inflammatory and 30-100 non-inflammatory lesions.
  • IGA 5 point scale – moderate or severe (grade 3 or 4).
• Exclusion criteria :
  • Subject is pregnant, lactating, or is planning to become pregnant during the study period.
  • Subject has any skin pathology or condition that could interfere with the evaluation of the test products or requires the use of interfering topical or systemic therapy.
  • Subject has greater than 2 facial nodules.
  • Subject has nodulcystic acne.
  • Subject has any condition which, in the investigator’s opinion, would make it unsafe for the subject to participate in this study.
  • Subject is currently enrolled in an investigational drug or device study.
  • Subject has received an investigational drug or has been tested with an investigational device within 30 days prior to the initiation of treatment (baseline).

• In the Table, the clinical and demographic characteristics. of the patients.

Primary Outcome Measures

• The primary outcome measure was evaluation of any change in facial acne vulgaris, as reflected in the percent change in inflammatory lesions at week 12, to identify a change from baseline and to determine if there was a statistically significant difference between clascoterone topical 1% cream and vehicle.

Secondary Outcome Measures

• The secondary outcome measure was assessment for change in facial acne vulgaris, as reflected in the percent change in non- inflammatory lesions at week 12, to identify a change from baseline and to determine if there was a statistically significant difference between clascoterone topical 1% cream and vehicle.

Drugs/Procedures Used

• A 12-week phase 3 study was conducted in subjects aged ≥9 years with moderate to severe acne, followed by 9-month open label safety extension.
• Patients were randomly assigned to clascoterone 1% topical cream or cream vehicle (1:1) for 12 weeks of treatment, during which they were to self-apply, twice daily in the morning and evening.
• The co-primary efficacy endpoints assessed were the proportion of subjects in each group with at least a two-point reduction in IGA from baseline and IGA score of 0 (clear) or 1 (almost clear) at week 12.
• Participants were evaluated for an absolute change from baseline in non-inflammatory lesions at week 12, as well as for an absolute change from baseline in inflammatory lesions at week 12.

• For the outcome measure of non-inflammatory lesions at week 12, the cohort treated with clascoterone 1% topical cream demonstrated a 29.8% reduction compared to an 18.9% reduction for vehicle, reflecting a statistically significant improvement.
• For the outcome measure of inflammatory lesions at week 12, the cohort treated with clascoterone 1% topical cream demonstrated a 46.2% reduction compared to an 32.7% reduction for vehicle, reflecting a statistically significant improvement.
• Treatment-emergent adverse events (TEAEs) for the impacted 11.1% of the clascoterone cohort (2.6% moderate, none severe) compared to 12.7% of vehicle cohort (4.3% moderate, <1% severe). Local skin reactions consisted of mild erythema.

• Clascoterone 1% topical cream treatment resulted in a clinically significant reduction in both inflammatory and non-inflammatory skin lesions over 12 weeks in both children and adults, thereby demonstrating efficacy.
• Treatment with clascoterone 1% topical cream produced a low rate of TEAEs which were not generally severe, thereby demonstrating safety.