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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Nektar Therapeutics

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Immune System Diseases [C20]

Trial duration

25 Apr 2024 → ongoing

Decision date (initial)

2024-04-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Nektar Therapeutics

External identifiers

EU CT number

2023-507456-69-00

ClinicalTrials.gov

NCT06136741

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

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 objectives 1

1. -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

Conditions and MedDRA coding

Atopic Dermatitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. 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, at least 18 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 ≥ 16.0 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).
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 (eg, 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, eg, 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,eg, 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, eg, skin atrophy, allergic reaction, or systemic effects that, in the opinion of the Investigator, outweigh the benefits of retreatment.

Exclusion criteria 5

1. 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. • 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 at any time 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.
2. • 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.
3. 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 eligibility criteria are met. Enrollment of patients with other uncomplicated local infections should be discussed with the Sponsor’s designated Medical Monitor. • Have had any of the following types of infection within 12 weeks prior to the Screening Visit (Visit 1) or develops any of these infections before the Randomization Visit (Visit 2): a) serious (requiring hospitalization, or intravenous or equivalent oral antibiotic treatment, or both) b) opportunistic (as defined in Winthrop, 2015) Note: Herpes zoster is considered active and ongoing until all vesicles are dry and crusted over. c) Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer) d) Recurring (including, but not limited to, herpes simplex, herpes zoster, recurring cellulitis, chronic osteomyelitis). Note: Patients with only recurrent mild and uncomplicated oral herpes, or genital herpes, or both may be discussed with the Sponsor’s designated Medical Monitor and considered for enrollment if other study eligibility criteria are met.
4. Diagnostic assessments • Have any of the following specific abnormalities on screening laboratory tests: a) serum creatinine, alanine transaminase (ALT), or aspartate transaminase (AST) > 2 × upper limit of normal (ULN) b) alkaline phosphatase (ALP) ≥ 2 × ULN c) total bilirubin level (TBL) ≥ 1.5 × ULN d) hemoglobin < 10.0 g/dL e) eosinophilia (absolute eosinophil count) > 1000 cells/μL f) estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] Creatinine Equation) (FDA 2020; NKF 2021). Note: For repeat testing of screening laboratory tests, see Section 4.4.1.
5. • Have other laboratory test results at screening (Visit 1) which are outside the normal reference range for the population or study site and, in the opinion of the Investigator, indicate unacceptable risk for the patient’s safety in the study. Other previous or current medical conditions • Any malignancies or history of malignancies within 5 years prior to randomization (except for basal cell or squamous epithelial carcinomas of the skin that have been sucessfully treated with no evidence of metastatic disease for 3 years or cervical carcinoma in situ that has been sucessfully treated, with no evidence of recurrence within the 3 years prior to randomization). • Have a history of any of the following within 12 months before the Screening Visit (Visit 1): a) myocardial infarction b) unstable ischemic heart disease c) cerebrovascular accident d) stroke, or e) New York Heart Association Stage III or IV heart failure.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean percent change in EASI from baseline at Week 16

Secondary endpoints 4

1. 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
2. Mean change from baseline over the period between Week 0 and Week 104 in • EASI • SCORAD • BSA involvement
3. Mean percent change from baseline over the period between Week 0 and Week 104 in • EASI • SCORAD • BSA involvement
4. 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)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Nektar Therapeutics

Sponsor organisation

Nektar Therapeutics

Address

455 Mission Bay Boulevard South

City

San Francisco

Postcode

94158-2158

Country

United States

Scientific contact point

Organisation

Nektar Therapeutics

Contact name

Study Director

Public contact point

Organisation

Nektar Therapeutics

Contact name

Study Director

Third parties 15

Locations

7 EU/EEA countries · 63 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 157 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

16 submissions — initial application plus substantial / non-substantial modifications