Nektar Therapeutics has completed target enrollment in its REZOLVE-AD Phase 2b study of rezpegaldesleukin in patients with moderate-to-severe atopic dermatitis (AD).
Rezpegaldesleukin is a first-in-class interleukin-2 receptor (IL-2R) agonist that proliferates and activates regulatory T cells (Tregs) with promising dose-dependent clinical activity in multiple skin disease settings.
Results from multiple clinical trials showed that rezpegaldesleukin safely and dose-dependently increased Tregs and rapidly improved measurable exploratory disease outcomes in patients with moderate-to-severe AD that were largely durable for at least 36 weeks after ceasing treatment, demonstrating proof-of-concept in this indication.
Proof-of-concept efficacy and safety data from a Phase 1b study of rezpegaldesleukin in atopic dermatitis patients were presented at the 2023 EADV Congress.
The REZOLVE-AD study enrolled patients with moderate-to-severe AD who had not previously received treatment with biologic or Janus kinase (JAK) inhibitor therapies. Patients were randomized across three different dose regimens of rezpegaldesleukin or placebo for a 16-week induction treatment period. Following this period, patients who meet an Eczema Area and Severity Index (EASI) score threshold for advancement to maintenance are re-randomized to one of two maintenance regimens at their original dose level to receive maintenance therapy either once a month or once every three months.
The primary endpoint of the Phase 2b study is mean improvement in EASI score at the end of the 16-week induction treatment period. Secondary endpoints include the proportion of patients achieving Validated Investigator Global Assessment (vIGA-AD) of 0 or 1, those achieving EASI-75, and those achieving a greater than or equal to a 4-point improvement in Itch Numeric Rating Scale (NRS).
This trial was initiated in October 2023. Patients were enrolled across approximately 110 sites globally with: 67% enrolled in the European countries of Poland, Bulgaria, Germany, Czechia, Spain, Croatia and Hungary; 17% enrolled in the United States; 11% enrolled in Canada; and 5% enrolled in Australia. Patient randomization was stratified based on baseline disease severity measured by vIGA-AD and geographic region.
Enrollment criteria in the study included a minimum EASI score of 16.0, a minimum Body Surface Area (BSA) of 10% and a minimum vIGA-AD of 3 at both screening and randomization. Patients who experienced an unstable course of atopic dermatitis between screening and randomization per investigator assessment were excluded from the study.
“We are pleased to announce that we reached our target enrollment for our 396-patient Phase 2b trial of rezpegaldesleukin,” says Howard W. Robin, President and CEO of Nektar Therapeutics, in a news release. “We are grateful to the patients and physicians whose strong interest in this novel mechanism, together with the proof-of-concept clinical data, led to completing enrollment of the study in just 14 months. Less than 10% of the 30 million atopic dermatitis patients who can receive biologics in the US and Europe are currently receiving treatment and we believe that novel mechanisms are key to helping more patients with this chronic and serious skin disorder. We look forward to announcing the topline data from the 16-week induction treatment period in this study in the second quarter of 2025.”
