Safety and Efficacy of a Novel Combination Cream (GN-037) in Healthy Volunteers and Patients with Plaque Psoriasis: A Phase 1 Trial.

Abstract

Psoriasis is a common skin disorder associated with physical and psychological burdens. Visible disfiguration can trigger a negative reaction which can cause much of the readily measurable psychological burden of the disease. Although many biological treatments provide some success in the initial clearance of lesions, there is a dispute about the long-term maintenance of the disease, as no current biological treatment has been shown to be curative. Topical therapies are still the most widely used agents as first-line and maintenance treatment for psoriasis. The present study aimed to investigate the safety, tolerability, and, to some extent, efficacy of GN-037 cream in patients with psoriasis and healthy volunteers. A randomized, double-blind, single-center, placebo-controlled phase 1 clinical study was conducted to evaluate the safety, tolerability, and clinical efficacy of GN-037 cream topically applied twice daily for 2weeks in healthy subjects (n = 12) and patients (n = 6) diagnosed with plaque-type psoriasis. Six healthy subjects received placebo. Patients with plaque psoriasis were evaluated by a dermatologist, and Physician Global Assessment (PGA) score was required to be ≥ 3 (moderate psoriasis) at screening. A total of 31 adverse events (AEs) occurred in 13 participants during the study: 9 AEs in healthy subjects receiving GN-037 cream, 3 AEs in healthy subjects receiving placebo, and 1 AE in one psoriatic patient. The most frequently reported AEs were reactions at the application site, including erythema, exfoliation, pruritus, and burning sensation. During the baseline evaluation, one patient had a PGA score of 3 (moderate) and five patients had a PGA score of 4 (severe). On day 14, in treatment, four patients experienced second grade and two patients third grade improvements compared with baseline, indicating a shift of patients from moderate and severe disease to mild disease and to almost clear (score 2 or 1). There were slight increases in plasma tumor necrosis factor (TNF)-α, interleukin-17 (IL-17) and interleukin-23 (IL-23) levels in both healthy volunteers and patients throughout the study, as compared with baseline. The results of this phase 1 trial conducted in 18 healthy volunteers and 6 patients with plaque psoriasis demonstrated a favorable safety and tolerability profile for GN-037; therefore, further clinical development of GN-037 in a phase 2 clinical trial has been initiated in patients with mild to moderate plaque psoriasis (NCT05706870). NCT05428202.