729 - A phase 2b, randomized, double-blinded, parallel-group, placebo-controlled, international, multicenter, study to evaluate the efficacy and safety of rezpegaldesleukin in adults with moderate-to-severe atopic dermatitis

Abstract Introduction & Objectives Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder. Dysfunction of regulatory T cells (Treg) may play a role in AD immunopathogenesis.1 Rezpegaldesleukin (REZPEG: NKTR-358) is a polyethylene glycol (PEG)-conjugated recombinant human interleukin 2 (rhIL-2) with the ability to selectively promote the activation and up-to 12-fold expansion of Tregs, while having relatively minimal effect on conventional T cells (Tcons).2 It represents a potential novel therapeutic approach for patients with moderate-to- severe AD. A Phase 1b study of REZPEG for patients with moderate-to-severe AD demonstrated a rapid time to response (2-4 weeks) during induction therapy and a prolonged durability of response, i.e., throughout the 36- week follow-up after cessation of therapy.3 These results support further development of REZPEG for patients with AD. Objective Evaluate the efficacy and safety of REZPEG in patients with moderate-to-severe AD. Materials & Methods This Phase 2b, randomized, double-blinded, placebo-controlled, international, multicenter study of REZPEG vs placebo enrolls biologic and JAK-inhibitor (JAKi) naïve adults with moderate-to-severe AD, defined by a baseline Eczema Area and Severity Index (EASI) score of ≥16, an Investigator’s Global Assessment (IGA) AD score of ≥3, affected total body surface area (BSA) of ≥10%, and chronic AD history of at least one year. Patients are randomized in a 3:3:3:2 ratio to three different REZPEG dosing regimens or placebo, administered subcutaneously during the induction phase. Responders achieving EASI50 post-induction are re-randomized to maintenance dosing every 4 or 12 weeks. Non-responders or those experiencing acute exacerbations are transferred to an open-label rescue arm receiving REZPEG. The primary outcome is the least squares mean percentage reduction in EASI from baseline at the end of induction. Secondary and exploratory endpoints include proportions achieving IGA 0/1 with a ≥2 point reduction, EASI75, EASI90, EASI50, itch relief (≥4 point improvement on the Numerical Rating Scale), % BSA improvement, safety, tolerability, patient-reported outcomes (PROs), pharmacokinetics, and pharmacodynamics. Results Trial ongoing (NCT06136741). Conclusion REZPEG represents an innovative approach to stimulate regulatory T cells, potentially offering lasting benefits for patients with moderate-to-severe AD. This Phase 2b trial seeks to define the optimal dosing schedule and further establish the efficacy and safety profile of REZPEG in a population new to biologic and JAK inhibitor therapies.

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Publication Details

Journal
British Journal of Dermatology
Published
2024-08-01
DOI
https://doi.org/10.1093/bjd/ljae266.102
Citations
1
Primary Topic
Dermatology and Skin Diseases
Type
article
Field-Weighted Citation Impact
0.53
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article

729 - A phase 2b, randomized, double-blinded, parallel-group, placebo-controlled, international, multicenter, study to evaluate the efficacy and safety of rezpegaldesleukin in adults with moderate-to-severe atopic dermatitis

Dedee Frances Murrell, Ricardo Tan, Melinda Gooderham, David Rosmarin et al.
1 citations
British Journal of Dermatology
Dermatology and Skin Diseases
0.53
article

729 - A phase 2b, randomized, double-blinded, parallel-group, placebo-controlled, international, multicenter, study to evaluate the efficacy and safety of rezpegaldesleukin in adults with moderate-to-severe atopic dermatitis

Dedee Frances Murrell, Ricardo Tan, Melinda Gooderham, David Rosmarin, Jonathan Zalevsky, Stephen M. Schleicher, Trinidad Montero‐Vílchez, Charles W Lynde, Maryam Shayesteh Alam, Sohail S. Chaudhry, Michael Sticherling, Craig A. Rohan, Pablo Fernández‐Peñas, Suzana Ljubojević Hadžavdić, Vivian Laquer, Ansgar Weyergraf, Adam Reich, Juan Ruano, Mary Tagliaferri, Lucinda M Elko-Simms, Maxwell Benjamin Sauder, Adelaide A. Hebert, Spyridon Gkalpakiotis, Neil S. Sadick, Christie Fanton, Wojciech Baran, Danni Yu, Zachary Lee, Andreas Wollenberg, Yi Liu, Telegdy Eniko, Wang Waltz, Jacek C Szepietowski, Timothy Rodgers, Jenny Gilbert, C. Jue, Michael Sebastian, James Q Del Rosso, William Philip Werschler
article en
1 citations

Abstract

Abstract Introduction & Objectives Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder. Dysfunction of regulatory T cells (Treg) may play a role in AD immunopathogenesis.1 Rezpegaldesleukin (REZPEG: NKTR-358) is a polyethylene glycol (PEG)-conjugated recombinant human interleukin 2 (rhIL-2) with the ability to selectively promote the activation and up-to 12-fold expansion of Tregs, while having relatively minimal effect on conventional T cells (Tcons).2 It represents a potential novel therapeutic approach for patients with moderate-to- severe AD. A Phase 1b study of REZPEG for patients with moderate-to-severe AD demonstrated a rapid time to response (2-4 weeks) during induction therapy and a prolonged durability of response, i.e., throughout the 36- week follow-up after cessation of therapy.3 These results support further development of REZPEG for patients with AD. Objective Evaluate the efficacy and safety of REZPEG in patients with moderate-to-severe AD. Materials & Methods This Phase 2b, randomized, double-blinded, placebo-controlled, international, multicenter study of REZPEG vs placebo enrolls biologic and JAK-inhibitor (JAKi) naïve adults with moderate-to-severe AD, defined by a baseline Eczema Area and Severity Index (EASI) score of ≥16, an Investigator’s Global Assessment (IGA) AD score of ≥3, affected total body surface area (BSA) of ≥10%, and chronic AD history of at least one year. Patients are randomized in a 3:3:3:2 ratio to three different REZPEG dosing regimens or placebo, administered subcutaneously during the induction phase. Responders achieving EASI50 post-induction are re-randomized to maintenance dosing every 4 or 12 weeks. Non-responders or those experiencing acute exacerbations are transferred to an open-label rescue arm receiving REZPEG. The primary outcome is the least squares mean percentage reduction in EASI from baseline at the end of induction. Secondary and exploratory endpoints include proportions achieving IGA 0/1 with a ≥2 point reduction, EASI75, EASI90, EASI50, itch relief (≥4 point improvement on the Numerical Rating Scale), % BSA improvement, safety, tolerability, patient-reported outcomes (PROs), pharmacokinetics, and pharmacodynamics. Results Trial ongoing (NCT06136741). Conclusion REZPEG represents an innovative approach to stimulate regulatory T cells, potentially offering lasting benefits for patients with moderate-to-severe AD. This Phase 2b trial seeks to define the optimal dosing schedule and further establish the efficacy and safety profile of REZPEG in a population new to biologic and JAK inhibitor therapies.

British Journal of DermatologyVol. 191(Supplement_2)
The University of Sydney (AU), University Hospital Centre Zagreb (HR), University of Zagreb (HR), Friedrich-Alexander-Universität Erlangen-Nürnberg (DE), University of Toronto (CA), Wright State University (US), University of Washington (US), Queen's University (CA), Cornell University (US), Charles University (CZ), Nektar Therapeutics (United States) (US), Westmead Hospital (AU), Wroclaw Medical University (PL), Barrie Urology Group (CA), California Allergy and Asthma Medical Group (US), Lynde Centre for Dermatology (CA), DermDox Dermatology Centers (US), Hospital Universitario Virgen de las Nieves (ES), Hospital Universitario Reina Sofía (ES), Mahlo (Germany) (DE), Markusovszky Egyetemi Oktatókórház (HU), Sadick Research Group (US), Center for Clinical Research (United States) (US), University Hospital Kralovske Vinohrady (CZ), Dermatology Research Center (US), Weill Cornell Medicine (US), Indiana University School of Medicine, Indiana University – Purdue University Indianapolis (US), Ludwig-Maximilians-Universität München (DE), The University of Texas Health Science Center at Houston (US), The University of Notre Dame Australia (AU), University of Rzeszów (PL)
Good health and well-being
Openalex Percentile: Top 30%
Dermatology and Skin Diseases
0.53
DOISourceOpenAlex
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