A Phase 3 Study of Rezpegaldesleukin (NKTR-358) for Patients ≥ 12 Years of Age With Moderate-to-Severe Atopic Dermatitis (ZENITH AD-1)

A Phase 3, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Rezpegaldesleukin (NKTR-358) Monotherapy in the Treatment of Patients ≥ 12 Years of Age With Moderate-to-Severe Atopic Dermatitis

This is an interventional, randomized, parallel group, treatment, Phase 3, double blind study to assess the effect of Rezpegaldesleukin in participants 12 years of age or older with moderate to severe atopic dermatitis, as compared to placebo.

The estimated participant overall duration is approximately 15 months.

Study Overview

• Status: Recruiting
• Conditions: Moderate-to-Severe Atopic Dermatitis
• Intervention / Treatment: Drug: Rezpegaldesleukin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 510
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Nektar Recruitment; Phone Number: 855-482-8676; Email: StudyInquiry@nektar.com

Study Locations

• United States
  • Florida
    • St. Petersburg, Florida, United States, 33714
      • Recruiting
      • Nektar Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female patients, ≥ 12 years of age on the day of signing the informed consent form and weighing ≥ 40 kg prior to randomization at Baseline
• Chronic atopic dermatitis (AD) defined as onset of AD signs and symptoms ≥ 12 months prior to Screening as determined by the Investigator through patient interview and/or review of medical history at the Screening Visit
• Patients must meet the following AD severity criteria:
• IGA score ≥ 3 (scale of 0 to 4) at Screening and Baseline
• ≥ 10.0% of BSA involvement at Screening and Baseline
• EASI ≥ 16.0 at Screening and Baseline
• Are candidates for systemic therapy and have history, documented by a physician and/or the Investigator, of inadequate response to existing topical medications within 6 months preceding Screening, or history of intolerance to a topical therapy
• Provide written, informed consent to participate in the study and follow the study procedures, including compliance with the use of highly effective contraceptives

Exclusion Criteria:

• Are currently experiencing or have a history of concomitant skin conditions other than AD, including skin infection in the area affected by the patient's AD that requires treatment with systemic antimicrobial therapy
• Are currently experiencing or have a history of unstable course of AD
• History of chronic idiopathic urticaria at any time or urticaria from other causes within 4 weeks prior to randomization at the Baseline Visit.
• Have a history of TCS use suggestive of a high risk for topical corticosteroid (TCS) withdrawal
• Have received any of the following treatments at any time before Screening: aldesleukin; investigational IL-2 analog; systemic biologic; oral JAKi; or any prior investigational agent for AD
• Have a current or recent acute, active infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blinded Induction Period: Rezpegaldesleukin every 2 weeks; Rezpegaldesleukin every 2 weeks during the induction period	Drug: Rezpegaldesleukin; Pharmaceutical form: Injection solution Route of administration: subcutaneous; Other Names: NKTR-358
Placebo Comparator: Blinded Induction Period: Placebo; Placebo every 2 weeks during the induction period	Drug: Placebo; Pharmaceutical form: Injection solution Route of administration: subcutaneous
Experimental: Blinded Maintenance Period: Rezpegaldesleukin every 4 weeks; Rezpegaldesleukin every 4 weeks during the maintenance period	Drug: Rezpegaldesleukin; Pharmaceutical form: Injection solution Route of administration: subcutaneous; Other Names: NKTR-358
Experimental: Blinded Maintenance Period: Rezpegaldesleukin every 12 weeks; Rezpegaldesleukin every 12 weeks during the maintenance period	Drug: Rezpegaldesleukin; Pharmaceutical form: Injection solution Route of administration: subcutaneous; Other Names: NKTR-358
Placebo Comparator: Blinded Maintenance Period: Placebo; Placebo every 4 weeks during the maintenance period	Drug: Placebo; Pharmaceutical form: Injection solution Route of administration: subcutaneous
Experimental: Open-Label Escape; Rezpegaldesleukin at a frequency determined by the investigator during the open-label escape	Drug: Rezpegaldesleukin; Pharmaceutical form: Injection solution Route of administration: subcutaneous; Other Names: NKTR-358

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
US only: Number of participants with an Investigator's Global Assessment (IGA) score of 0 or 1 and reduction ≥ 2 points from baseline at Week 24	The IGA scale ranges from 0 to 4, with higher score indicating more severe disease.	Week 0 and Week 24
Non-US regions only: Number of participants with an Investigator's Global Assessment (IGA) score of 0 or 1 at Week 24	The IGA scale ranges from 0 to 4, with higher score indicating more severe disease.	Week 0 and Week 24
Non-US regions only: Number of participants with a ≥ 75% reduction in Eczema Area and Severity Index (EASI) score from baseline at Week 24 (EASI-75)	The EASI scores range from 0 to 72, with higher scores indicating more severe atopic dermatitis.	Week 0 and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
US only: Number of participants with a ≥ 75% reduction in EASI score from baseline at Week 24 (EASI-75)	The EASI scores range from 0 to 72, with higher scores indicating more severe atopic dermatitis.	Week 0 and Week 24
Number of participants with a ≥ 90% reduction in EASI score from baseline at Week 24 (EASI-90)	The EASI scores range from 0 to 72, with higher scores indicating more severe atopic dermatitis.	Week 0 and Week 24
Number of participants at week 6 achieving a 4-point or greater improvement in Itch numerical rating scale (NRS) in the subset of participants with a 4-point or greater Itch NRS at baseline	The itch NRS goes from 0 to 10, with higher score indicating more severe itch.	Week 0 and Week 6
Number of participants at week 24 achieving a 4-point or greater improvement in Itch numerical rating scale (NRS) in the subset of participants with a 4-point or greater Itch NRS at baseline	The itch NRS goes from 0 to 10, with higher score indicating more severe itch.	Week 0 and Week 24
Number of participants at week 6 achieving a 4-point or greater improvement in Skin Pain numerical rating scale (NRS) in the subset of participants with a 4-point or greater Skin Pain NRS at baseline	The Skin Pain NRS goes from 0 to 10, with higher score indicating more severe pain.	Week 0 and Week 6
Number of participants at week 24 achieving a 4-point or greater improvement in Skin Pain numerical rating scale (NRS) in the subset of participants with a 4-point or greater Skin Pain NRS at baseline	The Skin Pain NRS goes from 0 to 10, with higher score indicating more severe pain.	Week 0 and Week 24
Number of participants at week 6 achieving a 1.25-point or greater improvement in Atopic Dermatitis Sleep Scale Question 1 (ADSS Q1) in the subset of participants with a 1.25-point or greater ADSS Q1 at baseline	The ADSS Q1 goes from 0 to 4, with higher score indicating more difficulty sleeping.	Week 0 and Week 6
Number of participants at week 24 achieving a 1.25-point or greater improvement in ADSS Q1 in the subset of participants with a 1.25-point or greater ADSS Q1 at baseline	The ADSS Q1 goes from 0 to 4, with higher score indicating more difficulty sleeping.	Week 0 and Week 24
Change in Asthma Control Questionnaire-5 (ACQ-5) score from baseline at Week 24 in the subpopulation of patients with a 0.5-point or greater ACQ-5 at baseline	The ACQ-5 goes from 0 to 6, with higher score indicating worse asthma control.	Week 0 and Week 24
Number of participants at week 24 achieving a 0.5-point or greater improvement in ACQ-5 in the subset of participants with a 0.5-point or greater ACQ-5 at baseline	The ACQ-5 goes from 0 to 6, with higher score indicating worse asthma control.	Week 0 and Week 24
Change in Sino-Nasal Outcome Test (SNOT-22) score from baseline at Week 24 in the subpopulation of patients with an 8.9-point or greater SNOT-22 at baseline	The SNOT-22 scores range from 0 to 110, with a higher score indicating more severe symptoms	Week 0 and Week 24
Number of participants at Week 24 achieving a 8.9-point or greater reduction from baseline in SNOT-22 in the subpopulation of patients with an 8.9-point or greater SNOT-22 at baseline	The SNOT-22 scores range from 0 to 110, with a higher score indicating more severe symptoms	Week 0 and Week 24
Number of participants at week 24 achieving an Adapted Investigator's Global Assessment (aIGA) response of 0 or 1	The aIGA scale ranges from 0 to 1, with a lower score indicating improvement in atopic dermatitis.	Week 0 and Week 24
Number of participants with treatment emergent adverse events (TEAEs)		Through participant study completion, approximately Week 56
Number of participants with treatment emergent serious adverse events		Through participant study completion, approximately Week 56
Number of participants with treatment related serious adverse events		Through participant study completion, approximately Week 56
Number of participants with treatment emergent adverse events of special interest		Through participant study completion, approximately Week 56
Number of participants with treatment related adverse events of special interest		Through participant study completion, approximately Week 56
Number of participants with TEAEs leading to treatment discontinuation		Through participant study completion, approximately Week 56
Number of participants with TEAEs leading to dose hold		Through participant study completion, approximately Week 56
Number of participants with TEAEs leading to dose modifications		Through participant study completion, approximately Week 56

Collaborators and Investigators

• Sponsor: Nektar Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 2, 2026
• First Submitted That Met QC Criteria: July 2, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 25-358-09; 2025-524925-42-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No