Moderate-to-Severe Atopic DermatitisPhase 3ZENITH AD-1NCT07690371
A Phase 3 Study of Rezpegaldesleukin (NKTR-358) for Patients ≥ 12 Years of Age With Moderate-to-Severe Atopic Dermatitis
A Phase 3 study testing Rezpegaldesleukin in people with Moderate-to-Severe Atopic Dermatitis, run by Nektar Therapeutics at 20 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Moderate-to-Severe Atopic Dermatitis
- What is being tested?
- Rezpegaldesleukin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 510 participants
- Where
- 20 sitesUnited States
- Study dates
- 29 Jun 2026to Dec 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
20 sites in 1 country. Contact the study team or a site near you to ask about taking part.
20 sites in 1 country
United States20 sites, 20 recruiting
- Recruiting
Nektar Investigative Site
Auburn Hills, Michigan, 48326-3396
- Recruiting
Nektar Investigative Site
Boca Raton, Florida, 33486
- Recruiting
Nektar Investigative Site
Boise, Idaho, 83706-1337
- Recruiting
Nektar Investigative Site
Bowling Green, Kentucky, 42104
- Recruiting
Nektar Investigative Site
Clifton, New Jersey, 07013
- Recruiting
Nektar Investigative Site
Fountain Valley, California, 92708-3701
- Recruiting
Nektar Investigative Site
Lafayette, Louisiana, 70508
- Recruiting
Nektar Investigative Site
Los Angeles, California, 90025-7014
- Recruiting
Nektar Investigative Site
Macon, Georgia, 31217-3865
- Recruiting
Nektar Investigative Site
New York, New York, 10023
- Recruiting
Nektar Investigative Site
New York, New York, 10128-0724
- Recruiting
Nektar Investigative Site
Normal, Illinois, 61761-6280
- Recruiting
Nektar Investigative Site
North Little Rock, Arkansas, 72117-2916
- Recruiting
Nektar Investigative Site
Oklahoma City, Oklahoma, 73118-2872
- Recruiting
Nektar Investigative Site
Omaha, Nebraska, 68144-5604
- Recruiting
Nektar Investigative Site
Owensboro, Kentucky, 42301
- Recruiting
Nektar Investigative Site
Phoenix, Arizona, 85037
- Recruiting
Nektar Investigative Site
St. Petersburg, Florida, 33714
- Recruiting
Nektar Investigative Site
Tampa, Florida, 33615-4537
- Recruiting
Nektar Investigative Site
Wilmington, North Carolina, 28405-2375
About this study
Official title: 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.
- Conditions
- Moderate-to-Severe Atopic Dermatitis
- Being tested
- Rezpegaldesleukin, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RezpegaldesleukinDrug
Also called NKTR-358
Pharmaceutical form: Injection solution Route of administration: subcutaneous
PlaceboDrug
Pharmaceutical form: Injection solution Route of administration: subcutaneous
| Study group | Role | What they receive |
|---|---|---|
| Blinded Induction Period: Rezpegaldesleukin every 2 weeks | Experimental | Rezpegaldesleukin every 2 weeks during the induction period Receives: Drug: Rezpegaldesleukin |
| Blinded Induction Period: Placebo | Placebo comparator | Placebo every 2 weeks during the induction period Receives: Drug: Placebo |
| Blinded Maintenance Period: Rezpegaldesleukin every 4 weeks | Experimental | Rezpegaldesleukin every 4 weeks during the maintenance period Receives: Drug: Rezpegaldesleukin |
| Blinded Maintenance Period: Rezpegaldesleukin every 12 weeks | Experimental | Rezpegaldesleukin every 12 weeks during the maintenance period Receives: Drug: Rezpegaldesleukin |
| Blinded Maintenance Period: Placebo | Placebo comparator | Placebo every 4 weeks during the maintenance period Receives: Drug: Placebo |
| Open-Label Escape | Experimental | Rezpegaldesleukin at a frequency determined by the investigator during the open-label escape Receives: Drug: Rezpegaldesleukin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Week 0 and Week 24
Secondary outcomes (21)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: Week 0 and Week 24
Number of participants with treatment emergent adverse events (TEAEs)
Measured: Through participant study completion, approximately Week 56
Number of participants with treatment emergent serious adverse events
Measured: Through participant study completion, approximately Week 56
Number of participants with treatment related serious adverse events
Measured: Through participant study completion, approximately Week 56
Number of participants with treatment emergent adverse events of special interest
Measured: Through participant study completion, approximately Week 56
Number of participants with treatment related adverse events of special interest
Measured: Through participant study completion, approximately Week 56
Number of participants with TEAEs leading to treatment discontinuation
Measured: Through participant study completion, approximately Week 56
Number of participants with TEAEs leading to dose hold
Measured: Through participant study completion, approximately Week 56
Number of participants with TEAEs leading to dose modifications
Measured: Through participant study completion, approximately Week 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2026
- Study start29 Jun 2026
- Primary completionMay 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Moderate-to-Severe Atopic DermatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized to rezpegaldesleukin or placebo for the Blinded Induction Period. The randomized double-blind study treatment duration will be up to 52 weeks. The final safety follow-up visit will be 8 weeks after the last dose for participants not entering the long-term extension study. At Week 24, patients who had an adequate response to treatment will be re-randomized to either rezpegaldesleukin (every 4 weeks or every 12 weeks), or placebo every 4 weeks as blinded maintenance treatment. Patients assigned to the every 12 week rezpegaldesleukin regimen will receive placebo injections during the intervening monthly visits to maintain the blind. Patients who did not achieve adequate response may receive open label escape with rezpegaldesleukin until the end of the treatment period. Additionally, patients who were re-randomized to the Blinded Maintenance Period and have worsening atopic dermatitis will have the option to receive open label escape therapy.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 510 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nektar Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07690371
- Sponsor's protocol ID
- 25-358-09
- Other IDs
- 2025-524925-42-00, 2025
- Acronym
- ZENITH AD-1
- Status last verified
- Oct 2026
- First submitted
- 2 Jul 2026
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No