Abstract

Introduction: Clindamycin phosphate (CLIN) 1.2%/adapalene (ADAP) 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) is the only triple-combination topical treatment approved for acne. These analyses assessed efficacy and safety of CAB gel by baseline acne severity vs component dyads and branded ADAP/BPO gel. Methods: These post hoc analyses used data pooled from two phase 2 and two phase 3, double-blind, 12-week studies (NCT03170388, NCT04892706, NCT04214639, NCT04214652). Eligible participants aged ≥9 years (≥12 years in NCT04892706) were randomized to once-daily CAB or vehicle gel. One phase 2 study included dyad combinations of CAB’s active ingredients: ADAP/BPO, CLIN/BPO, and CLIN/ADAP. The other phase 2 study included a head-to-head comparison of CAB gel and branded ADAP 0.3%/BPO 2.5% gel. Efficacy assessments included least-squares mean percent change from baseline in inflammatory/noninflammatory lesions and treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score [EGSS] and clear/almost clear skin). Safety assessments included treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability. Participants were categorized by baseline disease severity: moderate (EGSS = 3; n=1557) or severe (EGSS = 4; n=230). Results: After 12 weeks, inflammatory lesion reductions in participants with moderate acne were significantly greater with CAB (77.1%) than vehicle (54.1%; P<0.001), the 3 dyads (range, 64.4-69.4%; P≤0.001, all), and branded ADAP/BPO (72.8%; P<0.05). In the severe group, inflammatory lesion reductions with CAB (74.5%) were significantly greater than vehicle (44.4%; P<0.001) and 2 dyads (ADAP/BPO 63.9%, CLIN/BPO 61.3%; P<0.05), and similar to branded ADAP/BPO and CLIN/ADAP (75.4%/73.7%). Reductions in inflammatory lesions were greater than noninflammatory. Over half of CAB-treated participants with moderate disease achieved treatment success at week 12 (53.9% vs 19.5% vehicle; P<0.001), significantly greater than approximately one-third treated with dyads (range, 31.5-35.3%) or branded ADAP/BPO (38.1%; P≤0.001, all). Only CAB and CLIN/ADAP demonstrated significantly greater treatment success rates than vehicle in participants with severe acne at week 12 (30.9% and 34.0% vs 9.0%, respectively, P<0.05). Across all groups, most TEAEs were of mild to moderate severity. Mean cutaneous safety/tolerability scores were ≤1 (1 = mild) across severity groups. Conclusions: CAB gel demonstrated efficacy and safety in participants with both moderate and severe acne. Acne improvements with CAB were superior to the 3 dyads tested and branded ADAP/BPO in participants with moderate acne and generally numerically greater in participants with severe acne. To our knowledge, these analyses of combination topical acne treatments include data from the only double-blind, vehicle-controlled, head-to-head study to date. Funding: Ortho Dermatologics.