A phase 2, randomized, double-blind, vehicle-controlled trial of tapinarof cream in Japanese pediatric patients with atopic dermatitis

Abstract

Tapinarof is a nonsteroidal, topical, aryl hydrocarbon receptor agonist approved for the treatment of atopic dermatitis (AD) in Japanese patients aged ≥12 years. We evaluated the efficacy and safety of tapinarof in Japanese pediatric patients aged 2 to 11 years with AD in a phase 2, multicenter, randomized, double-blind, vehicle-controlled trial. Eligible patients (N = 121) were randomized 1:1:1 to receive tapinarof cream 0.5%, tapinarof cream 1%, or vehicle cream once daily for 8 weeks. At week 8, the least-squares mean percent change from baseline in Eczema Area and Severity Index (EASI) score (the primary endpoint) was -81.29% in the tapinarof 0.5% group, -77.62% in the tapinarof 1% group, and - 18.56% in the vehicle group. Reductions in EASI score at week 8 were significantly greater in the tapinarof groups than in the vehicle group (p < 0.0001 for both comparisons). The proportion of patients with ≥75% improvement from baseline in EASI score at week 8 was 77.5% in the tapinarof 0.5% group, 70.7% in the tapinarof 1% group, and 15.0% in the vehicle group. The proportion of patients who achieved an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear) with ≥2-grade improvement from baseline at week 8 was 32.5% in the tapinarof 0.5% group, 43.9% in the tapinarof 1% group, and 17.5% in the vehicle group. No treatment-related serious adverse events (AEs) were reported; all of the AEs were mild or moderate. Common AEs in tapinarof-treated patients included gastroenteritis, application site irritation, and nasopharyngitis. The incidence of trial discontinuations due to AEs was low in tapinarof-treated patients (one patient for each strength). In summary, both strengths of tapinarof cream demonstrated greater efficacy than vehicle cream and were well tolerated in Japanese pediatric patients with AD.

Keywords: aryl hydrocarbon receptor (AhR); atopic dermatitis; pediatric patients; phase 2 trial; tapinarof.

FIGURE 1

Trial design. AD, atopic dermatitis; BSA, body surface area; EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment; QD, once daily.

FIGURE 2

Patient disposition. QD, once daily.

FIGURE 3

Percent change from baseline in EASI score. (a) At week 8 (the primary endpoint), analyzed with the mixed effect models for repeated measures; (b) by trial visit, analyzed on the basis of observed cases. CI, confidence interval; EASI, Eczema Area and Severity Index; LS, least‐squares. *p < 0.0001 vs vehicle.

FIGURE 4

Key secondary endpoints. (a) EASI‐75 response rate at week 8, (b) IGA treatment success rate at week 8. EASI‐75 was defined as ≥75% improvement from baseline in EASI score. IGA treatment success was defined as an IGA score of 0 or 1 with ≥2‐grade improvement from baseline. Key secondary endpoints were analyzed on the basis of the first dataset out of 100 datasets where missing data were imputed by the multiple imputation. Data are presented with exact 95% CIs. *p = 0.0155 vs vehicle, **p < 0.0001 vs vehicle. CI, confidence interval; EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment.

FIGURE 5

Mean daily change in maximum pruritus score from baseline to week 4. The maximum pruritus score on an assessment day is defined as the greater of the daytime and nighttime scores. The baseline value for maximum pruritus score was defined as the mean value of daily maximum pruritus scores obtained during 7 days prior to the initiation of trial treatment. CI, confidence interval.