Moderate-to-Severe Atopic Dermatitis
Conditions
Brief 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.
Interventions
Pharmaceutical form: Injection solution Route of administration: subcutaneous
DRUGPlacebo
Pharmaceutical form: Injection solution Route of administration: subcutaneous
Sponsors
Nektar Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Week 0 and Week 24 | The IGA scale ranges from 0 to 4, with higher score indicating more severe disease. |
| Non-US regions only: Number of participants with an Investigator's Global Assessment (IGA) score of 0 or 1 at Week 24 | Week 0 and Week 24 | The IGA scale ranges from 0 to 4, with higher score indicating more severe disease. |
| 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) | Week 0 and Week 24 | The EASI scores range from 0 to 72, with higher scores indicating more severe atopic dermatitis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| US only: Number of participants with a ≥ 75% reduction in EASI score from baseline at Week 24 (EASI-75) | Week 0 and Week 24 | The EASI scores range from 0 to 72, with higher scores indicating more severe atopic dermatitis. |
| Number of participants with a ≥ 90% reduction in EASI score from baseline at Week 24 (EASI-90) | Week 0 and Week 24 | The EASI scores range from 0 to 72, with higher scores indicating more severe atopic dermatitis. |
| 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 | Week 0 and Week 6 | The itch NRS goes from 0 to 10, with higher score indicating more severe itch. |
| 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 | Week 0 and Week 24 | The itch NRS goes from 0 to 10, with higher score indicating more severe itch. |
| 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 | Week 0 and Week 6 | The Skin Pain NRS goes from 0 to 10, with higher score indicating more severe pain. |
| 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 | Week 0 and Week 24 | The Skin Pain NRS goes from 0 to 10, with higher score indicating more severe pain. |
| 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 | Week 0 and Week 6 | The ADSS Q1 goes from 0 to 4, with higher score indicating more difficulty sleeping. |
| 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 | Week 0 and Week 24 | The ADSS Q1 goes from 0 to 4, with higher score indicating more difficulty sleeping. |
| 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 | Week 0 and Week 24 | The ACQ-5 goes from 0 to 6, with higher score indicating worse asthma control. |
| 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 | Week 0 and Week 24 | The ACQ-5 goes from 0 to 6, with higher score indicating worse asthma control. |
| 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 | Week 0 and Week 24 | The SNOT-22 scores range from 0 to 110, with a higher score indicating more severe symptoms |
| 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 | Week 0 and Week 24 | The SNOT-22 scores range from 0 to 110, with a higher score indicating more severe symptoms |
| Number of participants at week 24 achieving an Adapted Investigator's Global Assessment (aIGA) response of 0 or 1 | Week 0 and Week 24 | The aIGA scale ranges from 0 to 1, with a lower score indicating improvement in atopic dermatitis. |
| 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 | — |
Countries
United States
Contacts
CONTACTNektar Recruitment
Outcome results
None listed