Secondary efficacy outcomes from a Phase IIb, randomized dose-finding study of tapinarof cream for the treatment of plaque psoriasis

Background/Objective: Despite available options for treating psoriasis, there is a need for effective topical therapies that can be used without concerns about body surface area (BSA) restrictions or long treatment duration. Tapinarof is a therapeutic aryl hydrocarbon receptor modulating agent (TAMA) under investigation for the treatment of psoriasis and atopic dermatitis. Method: This Phase IIb, double-blind, six-arm, vehicle-controlled randomized study (NCT02564042) assessed the efficacy and safety of tapinarof cream in subjects with plaque psoriasis. Subjects (aged 18-65 years) with 1 to 15 percent BSA involvement and Physician Global Assessment (PGA) score of at least 2 at baseline were randomized 1:1:1:1:1:1 to tapinarof cream 0.5% or 1% once (QD) or twice daily (BID) or vehicle QD or BID for 12 weeks with a four-week follow-up. The primary end point was the proportion of subjects achieving PGA score 0 or 1 and 2-grade or greater improvement in PGA score from baseline to Week 12, which has been reported elsewhere. Secondary efficacy outcomes reported here include a 50-percent or greater reduction in Psoriasis Area and Severity Index (PASI50), PASI90, mean change in PGA scores and total target lesion grading scores from baseline, and pruritus numeric rating scale (NRS) response. Results: Of 227 randomized subjects, 174 completed the study. Most subjects (80%) had a baseline PGA score of 3 (moderate). Mean PASI was 8.8. Higher PASI50 (all p<0.001) and PASI90 (p<0.01 except for the tapinarof 0.5% QD group) response rates were observed in all tapinarof groups versus vehicle at Week 12 and were maintained for four weeks after the end of study treatment. Mean improvements in PGA scores (all p<0.001) and total target lesion grading scores (all p<0.001) from baseline to Week 12 were significantly greater in all tapinarof groups versus vehicle and were maintained for four weeks after the end of study treatment (all p<0.01). In subjects with a baseline pruritus NRS item score of 4 or greater, pruritus NRS response at Week 12 (≥4 improvement in pruritus NRS score from baseline) was 55 to 73 percent (tapinarof 1% groups) and 56 to 57 percent (tapinarof 0.5% groups) versus 33 to 60 percent (vehicle groups). Most treatment-emergent adverse events were mild or moderate, and the most common (≥5%) across all groups were folliculitis (9%) and contact dermatitis (5%). Most incidences of folliculitis and contact dermatitis were mild or moderate. Conclusion: These results support the primary analysis showing that tapinarof cream was efficacious and well tolerated in adults with psoriasis.1 A Phase III study of tapinarof cream 1% QD in psoriasis is ongoing (NCT03956355).