A Phase 2b Study to Evaluate Rezpegaldesleukin (Rezpeg) in the Treatment of Adult Patients With Moderate-to-Severe Atopic Dermatitis (REZOLVE-AD)

Phase 1

Recruiting

Conditions: Atopic Dermatitis
MedDRA version: 20.0Level: PTClassification code: 10012438Term: Dermatitis atopic Class: 100000004858
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: CTIS2023-507456-69-00

Lead Sponsor: ektar Therapeutics

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 535

Inclusion Criteria

Full inclusion criteria are provided in Protocol Section 4.1. Informed consent and contraception requirements •Provide written, informed consent to participate in the study and follow the study procedures, including compliance with the use of highly effective contraceptives. Patient characteristics •Male or female patients, from 18 to 70 years of age, inclusive, on the day of signing the informed consent form. Note: In some jurisdictions, the legal age of consent for study participation is greater than 18 years. For sites in such jurisdictions, the legal age of consent will be used as the lower limit of the age range for this criterion. Disease-specific characteristics •Present with a diagnosis of AD at least 12 months prior to screening (Visit 1), as defined by the American Academy of Dermatology Guidelines of care for the management of atopic dermatitis: Section 1. Diagnosis and assessment of atopic dermatitis” (Eichenfield, 2014) •Patients must meet the following AD severity criteria: a)EASI = 16 at screening (Visit 1) and randomization (Visit 2). b)vIGA-AD score = 3 at screening (Visit 1) and randomization (Visit 2). c)= 10% of BSA involvement at screening (Visit 1) and randomization (Visit 2)., •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 (Visit 1), or history of intolerance to topical therapy as defined by at least 1 of the following: a)Inability to achieve good disease control defined as mild disease or better (e.g., vIGA-AD = 2) after use of at least a medium potency TCS for at least 4 weeks, or for the maximum duration recommended by the product prescribing information, e.g., 14 days for super potent TCS, whichever is shorter. Note: For the purpose of this criterion, a TCS may be used with or without TCI to address areas of disease. Note: Failing a nonbiologic systemic therapy intended to treat AD, e.g., cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, or other small molecules, within 6 months before screening (Visit 1) will be considered a surrogate for inadequate response to existing topical medications. b)a history of clinically significant adverse reactions with the use of TCS, e.g., skin atrophy, allergic reaction, or systemic effects that, in the opinion of the Investigator, outweigh the benefits of retreatment.

Exclusion Criteria

Full exclusion criteria are provided in Protocol Section 4.2. Skin conditions •Are currently experiencing or have a history of concomitant skin conditions other than AD (e.g., psoriasis or cutaneous lupus), that, in the opinion of the Investigator, would interfere with assessments or interpretation of the effect of study intervention on AD. Note: Patients with alopecia areata and/or vitiligo comorbidity are eligible for the study if, in the opinion of the Investigatory, it would not interfere with assessment or interpretation of the effect of study intervention on AD. •Are currently experiencing a skin infection in the area affected by the patient’s AD that requires treatment with, or is currently being treated with, topical antimicrobial therapy. Note: Patients who are not eligible (screen fail) due to this criterion should not be rescreened until at least 4 weeks after screen failure and at least 2 weeks after resolution of the infection. •History of chronic idiopathic urticaria or urticaria from other causes within 4 weeks prior to randomization Previous or current therapies •Have a history of TCS use suggestive of a high risk for TCS withdrawal (e.g., a history of prolonged or frequent use of moderate- to high-potency TCS, especially on the face [Hajar, 2015]), such that, in the opinion of the Investigator, the patient will be unable to withdraw and abstain from TCS for several weeks during the study., •Have received any of the following treatments at any time before Visit 1: a)aldesleukin b)investigational IL-2 analog c)oral Janus kinase (JAK) inhibitor for any indication, including, but not limited to, baricitinib, upadacitinib, abrocitinib, tofacitinib, and ruxolitinib, whether marketed or investigational d)systemic immune-modulating biologic therapy (including, but not limited to, dupilumab, tralokinumab, lebrikizumab, nemolizumab, rocatinlimab, etc.) whether marketed or investigational •Have received any of the following therapies during the specified time period (washout”) or are anticipated to require any of these therapies during the study: Table is provided in Protocol Section 4.2 •Are unstable with respect to use of chronic treatments (prescription or over the counter) to improve sleep: a)Have started or restarted using a sleep medication during the 2 weeks before the day of the first dose of study intervention b)Have changed the dose of a sleep medication during the 2 weeks before the day of the first dose of study intervention, or c)Are likely to need to start or change the dose of sleep medication during this study, in the opinion of the Investigator. Note: Individuals on a stable dose of sleep medication at screening may be eligible to be enrolled if other study entry criteria are met, but such individuals should remain on the stable dose throughout the study unless, in the Investigator’s opinion, the dose should be changed or stopped to address a safety concern., Previous or current infections •Have a current or recent acute, active infection. For at least 30 days prior to screening (Visit 1) and up to the Randomization Visit (Visit 2), patients must have no symptoms or signs of confirmed or suspected infection, and must have completed any appropriate anti-infective treatment. Note: Patients who have an oral, upper respiratory, or vaginal candida infection and who are being treated only symptomatically and not requiring systemic anti infectives may be considered for enrollment if other study eligibi

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy of each dose regimen of rezpegaldesleukin versus placebo as measured by the percent change from baseline in EASI in the treatment of biologic-naive patients with moderate-to-severe AD;Secondary Objective: -To compare the efficacy of rezpegaldesleukin versus placebo as measured by improvement in signs and/or symptoms in the treatment of biologic-naive patients with moderate-to-severe AD -To characterize the PK of rezpegaldesleukin in patients with moderate-to-severe AD -To describe the observed safety of rezpegaldesleukin in patients with moderate-to-severe AD;Primary end point(s): Mean percent change in EASI from baseline at Week 16

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Proportion of patients from baseline at Week 16 achieving •vIGA AD of 0 or 1 and at least a 2-point reduction. •EASI-75 •EASI 90 •EASI-50 •= 4-point improvement from baseline in Itch NRS in the subset of patients with = 4-point Itch NRS at baseline. •SCORAD-75 •SCORAD-50;Secondary end point(s):Mean change from baseline over the period between Week 0 and Week 54 in •EASI •SCORAD •BSA involvement;Secondary end point(s):Mean percent change from baseline over the period between Week 0 and Week 54 in •EASI •SCORAD •BSA involvement;Secondary end point(s):In addition, all of the above efficacy assessments will be further evaluated at other time points during induction therapy, maintenance therapy, and follow-up - Rezpegaldesleukin plasma concentrations at various time points assessed throughout the study. - Incidence of •Serious adverse events (SAEs) •Treatment-emergent adverse events (TEAEs)