Rezpegaldesleukin for Atopic Dermatitis
(REZOLVE-AD Trial)
Recruiting in Palo Alto (17 mi)
+210 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Nektar Therapeutics
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial tests a modified protein called rezpegaldesleukin in adults with moderate to severe atopic dermatitis. The treatment aims to help the immune system reduce skin inflammation and symptoms.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have used systemic immune modulating therapies for atopic dermatitis before joining the trial.
What data supports the idea that Rezpegaldesleukin for Atopic Dermatitis is an effective treatment?
The available research does not provide any data on Rezpegaldesleukin for Atopic Dermatitis. The studies mentioned focus on other treatments and conditions, such as leukemia and Crohn's disease, but do not include information on Rezpegaldesleukin's effectiveness for Atopic Dermatitis.
12345What safety data is available for Rezpegaldesleukin in treating atopic dermatitis?
The provided research does not contain specific safety data for Rezpegaldesleukin (also known as LY-3471851, NKTR-358, PEG-conjugated rhIL-2, REZPEG) in the treatment of atopic dermatitis. The articles focus on other treatments and therapeutic strategies for atopic dermatitis, such as Galectin-1, human IgE pentapeptide, and Tezepelumab, but do not mention Rezpegaldesleukin or its safety profile.
678910Eligibility Criteria
Adults aged 18-70 with moderate-to-severe atopic dermatitis (AD) for over a year, who haven't responded well to topical treatments. Participants must have an EASI score of 16+, IGA of 3 or 4, and BSA involvement of 10%+. Exclusions include other skin conditions, certain infections like HIV/Hepatitis, cancer history within the last five years (with exceptions), pregnancy/breastfeeding women, recent live vaccines, immune suppression issues, prior AD biologic treatments or severe illnesses.Inclusion Criteria
Able and willing to provide written informed consent
Able to complete patient questionnaires
Able and willing to comply with requested study visits and procedures
+3 more
Exclusion Criteria
I do not have severe illnesses like heart failure or kidney disease that would stop me from joining the study.
I haven't had any cancer except for certain skin cancers or cervical cancer in situ in the last 5 years.
Concurrent participation in any other investigational clinical study
+6 more
Participant Groups
The trial is testing Rezpegaldesleukin (Rezpeg), a pegylated form of interleukin-2 for treating AD. It's randomized and double-blind with four parallel groups: some get Rezpeg while others receive a placebo. The study includes initial treatment up to day 280 followed by safety follow-up until approximately day 378.
12Treatment groups
Experimental Treatment
Placebo Group
Group I: Escape Therapy (open-label)Experimental Treatment1 Intervention
Rezpegaldesleukin Dose Regimen A every 2 weeks during the maintenance period
Group II: Arm C2Experimental Treatment2 Interventions
Rezpegaldesleukin Dose Regimen C every 12 weeks during the maintenance period
Group III: Arm C1Experimental Treatment1 Intervention
Rezpegaldesleukin Dose Regimen C every 4 weeks during the maintenance period
Group IV: Arm CExperimental Treatment1 Intervention
Rezpegaldesleukin Dose Regimen C every 2 weeks during the induction period
Group V: Arm B2Experimental Treatment2 Interventions
Rezpegaldesleukin Dose Regimen B every 12 weeks during the maintenance period
Group VI: Arm B1Experimental Treatment1 Intervention
Rezpegaldesleukin Dose Regimen B every 4 weeks during the maintenance period
Group VII: Arm BExperimental Treatment2 Interventions
Rezpegaldesleukin Dose Regimen B every 4 weeks during the induction period
Group VIII: Arm A2Experimental Treatment2 Interventions
Rezpegaldesleukin Dose Regimen A every 12 weeks during the maintenance period
Group IX: Arm A1Experimental Treatment1 Intervention
Rezpegaldesleukin Dose Regimen A every 4 weeks during the maintenance period
Group X: Arm AExperimental Treatment1 Intervention
Rezpegaldesleukin Dose Regimen A every 2 weeks during the induction period
Group XI: Arm D1Placebo Group1 Intervention
Placebo every 4 weeks during the maintenance period
Group XII: Arm DPlacebo Group1 Intervention
Placebo every 2 weeks during the induction period
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Indiana Clinical Research CenterIndianapolis, IN
Great Lakes Research Group - 4497 Sheffield PlBay City, MI
Abys New Generation ResearchHialeah, FL
Dermatology on BloorToronto, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
Nektar TherapeuticsLead Sponsor
References
[Pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a prospective control trial]. [2021]To study the pharmacokinetic characteristics, clinical effect, and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in children with acute lymphoblastic leukemia (ALL).
Maintenance therapy with certolizumab pegol for Crohn's disease. [2022]Certolizumab pegol is a pegylated humanized Fab' fragment with a high binding affinity for tumor necrosis factor alpha that does not induce apoptosis of T cells or monocytes.
Pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor in children with acute leukaemia. [2021]This open-label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the treatment of chemotherapy-induced neutropenia in children with acute leukaemia.
Antibodies Predict Pegaspargase Allergic Reactions and Failure of Rechallenge. [2023]Label="PURPOSE">Pegaspargase (PEG-ASP) has largely replaced native Escherichia coli asparaginase (L-ASP) in the treatment of acute lymphoblastic leukemia because of its longer half-life and lower immunogenicity. Risk factors for allergic reactions to PEG-ASP remain unclear. Here, we identify risk factors for reactions in a front-line acute lymphoblastic leukemia trial and assess the usefulness of serum antibodies for diagnosing allergy and predicting rechallenge outcome.
Preclinical evaluation of the mono-PEGylated recombinant human interleukin-11 in cynomolgus monkeys. [2018]The mono-PEGylated recombinant human interleukin-11 (rhIL-11) was evaluated for its pharmacology and toxicology profile in non-human primates. This PEGylated IL-11 (PEG-IL11) showed a much prolonged circulating half-life of 67h in cynomolgus monkeys as compared to its un-PEGylated counterpart (~3h) through subcutaneous administration, implicating that a single injection of the recommended dose will effectively enhance thrombopoiesis in humans for a much longer period of time compared to rhIL-11 in humans (t1/2=6.9h). The toxicokinetics study of single dose and multiple doses showed that systemic exposure was positively correlated with the dosing level, implying that efficacy and toxicity were mechanism-based. A single high dose at 6.25mg/kg through subcutaneous route revealed tolerable and transient toxicity. Multiple-dose in monkeys receiving 0.3mg/kg weekly of the drug developed only mild to moderate toxicity. Major adverse events and immunogenicity in monkeys were only observed in the overdose groups. Bones were positively impacted; while reversible toxicities in heart, liver, kidney and lung observed were likely to be consequences of fluid retention. In summary, the PEG moiety on rhIL-11 did not elicit additional toxicities, and the drug under investigation was found to be well tolerated in monkeys after receiving a single effective dose of 0.1-0.3mg/kg through subcutaneous delivery, which may be allometrically scaled to a future clinical dose at 30-100μg/kg, creating a potential long acting, safer, and more convenient treatment approach based on rhIL-11.
Therapeutic pipeline for atopic dermatitis: End of the drought? [2017]Until the past year, our therapeutic armamentarium for treating atopic dermatitis (AD) was still primarily topical corticosteroids and, for more severe disease, systemic immunosuppressants. The pipeline of more targeted topical and systemic therapies is expanding based on our growing understanding of the mechanism for AD and is particularly focused on suppressing the skewed immune activation. Most agents are in phase 2 clinical trials. Crisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor, became available in late 2016 in the United States for mild-to-moderate AD, with other PDE4 inhibitors, an agonist of the aryl hydrocarbon receptor, Janus kinase inhibitors, and commensal organisms also in trials for topical application. The first highly effective mAb for AD, dupilumab, targets the IL-4/IL-13 receptor and was approved in early 2017 in the United States for moderate-to-severe adult AD. Other biologics similarly inhibit TH2 cytokines (thymic stromal lymphopoietin, IL-4, IL-5, IL-13, and the itch-specific cytokine IL-31 and their receptors) or TH22/TH17 cytokines, levels of which are increased in lesional skin. Orally administered small-molecule inhibitors that suppress inflammation (targeting chemoattractant receptor-homologous molecules expressed on TH2 lymphocytes, PDE4, the histamine 4 receptor, and Janus kinase) or specifically itching (eg, NK1R inhibitors) are also being studied. Comparing biomarkers with individual responses to experimental agents will help to determine subphenotypes within AD that predict prognosis and treatment responses.
Anti-inflammatory effect of galectin-1 in a murine model of atopic dermatitis. [2019]Atopic dermatitis (AD) is caused by both dysregulated immune responses and an impaired skin barrier. Although beta-galactoside-binding protein galectin-1 (Gal-1) has immunomodulatory effects in several inflammatory disorders, therapeutic strategies based on its anti-inflammatory properties have not been explored in AD. Thus, we evaluate pharmacological treatment with Gal-1 in the progression of an ovalbumin (OVA)-induced AD-like skin lesions. The skin of OVA-immunized male BALB/c mice was challenged with drops containing OVA on days 11, 14-18 and 21-24. Additionally, in the last week, a subset of animals was treated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamethasone (Dex). Treatment with rGal-1 decreased the clinical signs of dermatitis in BALB/c mice and diminished local eotaxin and IFN-γ levels. The treatment also suppressed the infiltration of eosinophils and mast cells, which was verified by reduced expression of mouse mast cell protease 6 (mMCP6) and eosinophil peroxidase (EPX). These localized effects are associated with extracellular signal-regulated kinase (ERK) activation and downregulation of endogenous Gal-1. The inhibition of disease progression induced by rGal-1 was also correlated with reduced plasma IL-17 levels. Our results demonstrate that rGal-1 is an effective treatment for allergic skin inflammation in AD and may impact the development of novel strategies for skin inflammatory diseases.
Safety and efficacy of human IgE pentapeptide. [2021]The safety, dosage and efficacy of human IgE pentapeptide (HEPP) was evaluated in 12 patients with IgE-mediated atopic disease. Statistically significant differences were observed in allergy symptom scores, allergy medication usage and skin test results between the HEPP treatment and placebo control groups. HEPP appears to be a safe, new therapeutic modality for the treatment of allergic disease.
Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial. [2022]Tezepelumab (AMG 157/MEDI9929), a first-in-class monoclonal antibody, targets thymic stromal lymphopoietin, a cytokine that is implicated in the pathogenesis of atopic dermatitis (AD).
[Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 (fingolimod) in combination with betamethasone ointment in NC/Nga mice]. [2015]The increasing incidence and prevalence of atopic dermatitis (AD) have led to a requirement for new means to treat the disease. We investigated the therapeutic efficacy of the novel immunomodulator FTY720 (Fingolimod), alone and in combination with betamethasone valerate ointment, in the NC/Nga mouse model of mite-induced intractable dermatitis.
Recombinant interferon gamma therapy for atopic dermatitis. [2019]Atopic dermatitis is characterized by immunologic abnormalities including evidence for reduced interferon gamma production. Therapeutic options for treatment of atopic dermatitis are limited and unsatisfactory. Previous open trials have suggested efficacy for recombinant interferon-gamma (rIFN-gamma) in treatment of severe atopic dermatitis. We describe the results of treatment with rIFN-gamma, assessing clinical, immunologic, and laboratory safety parameters in 83 patients with moderate to severe atopic dermatitis.
Peptidoglycan from Staphylococcus aureus induces IL-4 production from murine spleen cells via an IL-18-dependent mechanism. [2008]Atopic dermatitis (AD) is a chronic inflammatory skin disease with immunopathologic features that vary depending on the duration of the lesion. Skin lesions of AD patients show an increased number of Th2 cells in the dermis and superficial Staphylococcus aureus colonization. The purpose of this study was to predict the effects of peptido- glycan (PEG) from S. aureus on the induction of interleukin (IL)-4 production in AD patients.
Long-term therapy with recombinant interferon-gamma (rIFN-gamma) for atopic dermatitis. [2011]Interferon-gamma (IFN-gamma) is a potent cytokine that modulates IL-4-induced immune responses. Atopic dermatitis is associated with increased IgE levels and decreased IFN-gamma production. Recent phase I and phase II studies have suggested that short-term rIFN-gamma therapy is effective in the treatment of severe atopic dermatitis.
Immunopathogenesis of Atopic Dermatitis: Focus on Interleukins as Disease Drivers and Therapeutic Targets for Novel Treatments. [2023]Atopic dermatitis is a chronic, recurrent inflammatory skin disorder manifesting by eczematous lesions and intense pruritus. Atopic dermatitis develops primarily as a result of an epidermal barrier defect and immunological imbalance. Advances in understanding these pathogenetic hallmarks, and particularly the complex role of interleukins as atopic dermatitis drivers, resulted in achieving significant therapeutic breakthroughs. Novel medications involve monoclonal antibodies specifically blocking the function of selected interleukins and small molecules such as Janus kinase inhibitors limiting downstream signaling to reduce the expression of a wider array of proinflammatory factors. Nevertheless, a subset of patients remains refractory to those treatments, highlighting the complexity of atopic dermatitis immunopathogenesis in different populations. In this review, we address the immunological heterogeneity of atopic dermatitis endotypes and phenotypes and present novel interleukin-oriented therapies for this disease.