The novel protease inhibitor SRD441 ointment is not effective in the treatment of adult subjects with atopic dermatitis: results of a randomized, vehicle-controlled study.

BACKGROUND: There is evidence that excessive protease activity in the skin is an important factor in the development of atopic dermatitis. SRD44 is a topically formulated novel protease inhibitor that selectively inhibits Staphylococcal-derived aureolysin and matrix metalloproteinases (MMPs). METHODS: This was a double-blind, vehicle-controlled randomized trial conducted in thirteen hospital dermatology outpatient clinics in Germany (9), Bulgaria (3) and Finland (1). Ninety-three out of 103 screened adult subjects with confirmed atopic dermatitis affecting ≤ 20% of body surface area, with an IGA score of 2 or 3 at randomization were randomized following a washout period to either SRD441 ointment or matching vehicle twice daily for 28 days. The primary efficacy endpoint was the clearance of Atopic dermatitis (AD score of 0 or 1 IGA) at Day 21. Secondary endpoints included measures of SCORing Atopic Dermatitis, pruritus self-assessment, rescue medication use and occurrence of new exacerbations. A range of safety and tolerance endpoints were included. RESULTS: There were no significant treatment differences in IGA success rates at Day 21 (SRD441 ointment, 11.1%; vehicle ointment, 12.5%; P = 1.000). Evaluation of secondary efficacy variables revealed no clinical or important statistical differences between treatment groups. Eighteen subjects (19.4%) discontinued the study drug because of an AE (seven subjects [15.6%] in the SRD441 group and 11 subjects [22.9%] in the vehicle group). Twenty-seven subjects (60.0%) in the SRD441 group and 34 subjects (70.8%) in the vehicle group reported an adverse event (AE). CONCLUSIONS: SRD441 ointment did not demonstrate efficacy in the treatment of atopic dermatitis raising questions on the effectiveness of MMPs as a target for the treatment of atopic dermatitis. NCT00882245.