Rezpegaldesleukin for Atopic Dermatitis

(REZOLVE-AD Trial)

Not currently recruiting at 220 trial locations

Overseen By Nektar Recruitment

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nektar Therapeutics

Must not be taking: JAK inhibitors, Biologics

Disqualifiers: Other skin conditions, Malignancies, Immunosuppression, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new treatment, rezpegaldesleukin, for individuals with moderate to severe atopic dermatitis, a type of eczema that causes itchy, inflamed skin. The study tests various doses and schedules to determine the most effective one. Participants are randomly assigned to groups and may receive either the treatment or a placebo, which is a harmless pill without the treatment. Individuals who have had atopic dermatitis for at least a year and have not responded well to creams or ointments might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in eczema treatment.

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have used systemic immune modulating therapies for atopic dermatitis before, you cannot participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that rezpegaldesleukin, the treatment under study for atopic dermatitis, has a promising safety record. Previous studies found this treatment to be safe and well-tolerated. For instance, a combined safety review from nine different studies included both healthy volunteers and individuals with chronic inflammatory conditions. These studies reported that participants generally tolerated the treatment well at various dose levels.

Additionally, another study found that rezpegaldesleukin moved through the body consistently when administered in specific doses. This consistency suggests that the treatment behaves predictably in the body, which can indicate safety.

Overall, these findings suggest that rezpegaldesleukin is generally well-tolerated in humans. However, like any medical treatment, side effects may occur, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for atopic dermatitis?

Rezpegaldesleukin is unique because it targets the immune system differently than current treatments for atopic dermatitis. While most standard therapies focus on suppressing inflammation, such as topical corticosteroids or calcineurin inhibitors, Rezpegaldesleukin works by modifying the action of interleukin-2, a key player in immune regulation. This novel approach could lead to better control of symptoms with potentially fewer side effects. Researchers are excited about its potential to provide a more targeted and sustainable treatment option for patients with atopic dermatitis.

What evidence suggests that this trial's treatments could be effective for atopic dermatitis?

Research has shown that rezpegaldesleukin, which participants in this trial may receive, may help treat atopic dermatitis, a type of eczema. In one study, this treatment significantly improved eczema severity, as measured by a special index. Patients experienced a clear reduction in the spread and seriousness of their skin condition. The treatment increases regulatory T cells, a type of immune cell that helps reduce inflammation. Early results suggest it is both effective and safe for people with moderate to severe atopic dermatitis. ^{1 2 4 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Nektar Therapeutics

Are You a Good Fit for This Trial?

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-5 weeks

Induction

Participants receive induction therapy with rezpegaldesleukin or placebo for 16 weeks

16 weeks

Maintenance

Participants who respond to induction therapy are re-randomized for maintenance therapy

36 weeks

Posttreatment Follow-Up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Rezpegaldesleukin

Trial Overview 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.

How Is the Trial Designed?

Group I: Escape Therapy (open-label) Experimental Treatment 1 Intervention

Rezpegaldesleukin Dose Regimen A every 2 weeks during the maintenance period

Group II: Arm C2 Experimental Treatment 2 Interventions

Rezpegaldesleukin Dose Regimen C every 12 weeks during the maintenance period

Group III: Arm C1 Experimental Treatment 1 Intervention

Rezpegaldesleukin Dose Regimen C every 4 weeks during the maintenance period

Group IV: Arm C Experimental Treatment 1 Intervention

Rezpegaldesleukin Dose Regimen C every 2 weeks during the induction period

Group V: Arm B2 Experimental Treatment 2 Interventions

Rezpegaldesleukin Dose Regimen B every 12 weeks during the maintenance period

Group VI: Arm B1 Experimental Treatment 1 Intervention

Rezpegaldesleukin Dose Regimen B every 4 weeks during the maintenance period

Group VII: Arm B Experimental Treatment 2 Interventions

Rezpegaldesleukin Dose Regimen B every 4 weeks during the induction period

Group VIII: Arm A2 Experimental Treatment 2 Interventions

Rezpegaldesleukin Dose Regimen A every 12 weeks during the maintenance period

Group IX: Arm A1 Experimental Treatment 1 Intervention

Rezpegaldesleukin Dose Regimen A every 4 weeks during the maintenance period

Group X: Arm A Experimental Treatment 1 Intervention

Rezpegaldesleukin Dose Regimen A every 2 weeks during the induction period

Group XI: Arm D1 Placebo Group 1 Intervention

Placebo every 4 weeks during the maintenance period

Group XII: Arm D Placebo Group 1 Intervention

Placebo every 2 weeks during the induction period

Who Is Running the Clinical Trial?

Nektar Therapeutics

Lead Sponsor

Trials

59

Recruited

9,900+

Howard W. Robin

Nektar Therapeutics

Chief Executive Officer since 2007

B.S. in Accounting and Finance from Fairleigh Dickinson University

Dr. Dimitry Nuyten

Nektar Therapeutics

Chief Medical Officer since 2022

MD

Published Research Related to This Trial

In a study of 83 patients with moderate to severe atopic dermatitis, treatment with recombinant interferon-gamma (rIFN-gamma) for 12 weeks resulted in a significant improvement in symptoms, with 45% of patients showing over 50% improvement compared to 21% in the placebo group.

rIFN-gamma was found to be safe and well-tolerated, with manageable side effects such as headaches and chills, and it effectively reduced inflammation and eosinophil counts, indicating its potential as a therapeutic option for atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant interferon gamma therapy for atopic dermatitis. Hanifin, JM., Schneider, LC., Leung, DY., et al.[2019]

Recent advancements in the treatment of atopic dermatitis (AD) include the approval of dupilumab, a monoclonal antibody that targets the IL-4/IL-13 receptor, which has shown high efficacy for moderate-to-severe cases.

New therapies, such as crisaborole (a topical PDE4 inhibitor) and various biologics targeting specific cytokines involved in AD, are in development and may offer more targeted treatment options based on the underlying immune mechanisms of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic pipeline for atopic dermatitis: End of the drought? Paller, AS., Kabashima, K., Bieber, T.[2017]

Peptidoglycan (PEG) from Staphylococcus aureus significantly increases interleukin-4 (IL-4) production in mice, suggesting it may play a role in promoting a Th2-dominant immune response in atopic dermatitis (AD).

The study found that PEG not only induced IL-4 production but also correlated with increased IL-18 levels, indicating a potential mechanism by which PEG influences immune responses in AD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptidoglycan from Staphylococcus aureus induces IL-4 production from murine spleen cells via an IL-18-dependent mechanism. Matsui, K., Wirotesangthong, M., Nishikawa, A.[2008]

In a study of 17 children with acute lymphoblastic leukemia (ALL), pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) demonstrated a faster recovery of absolute neutrophil count (ANC) compared to standard rhG-CSF, indicating its potential efficacy in supporting immune recovery after chemotherapy.

Both PEG-rhG-CSF and rhG-CSF showed similar safety profiles, with no significant differences in adverse effects such as febrile neutropenia or infections, suggesting that PEG-rhG-CSF is a safe alternative for managing neutropenia in pediatric ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a prospective control trial]. Yang, WY., Liu, TF., Chen, XJ., et al.[2021]

Long-term treatment with recombinant interferon-gamma (rIFN-gamma) for severe atopic dermatitis in 15 patients over a minimum of 22 months resulted in significant improvements, with total body surface area involvement decreasing from 61.6% to 18.5%.

The therapy was found to be safe, with no significant laboratory abnormalities or growth issues reported, while also leading to a reduction in clinical severity scores from 11.4 to 6.3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term therapy with recombinant interferon-gamma (rIFN-gamma) for atopic dermatitis. Schneider, LC., Baz, Z., Zarcone, C., et al.[2011]

In a study involving 668 adults with moderate-to-severe Crohn's disease, those who received maintenance therapy with certolizumab pegol after an initial response were significantly more likely to maintain their response (62% vs. 34% for placebo) and achieve remission (48% vs. 29% for placebo) at 26 weeks.

Certolizumab pegol was effective regardless of concurrent treatments like glucocorticoids or immunosuppressants, but there were some safety concerns, including a 3% incidence of serious infections in the certolizumab group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance therapy with certolizumab pegol for Crohn's disease. Schreiber, S., Khaliq-Kareemi, M., Lawrance, IC., et al.[2022]

The mono-PEGylated recombinant human interleukin-11 (PEG-IL11) demonstrated a significantly longer half-life of 67 hours in cynomolgus monkeys compared to the un-PEGylated version, suggesting it could enhance thrombopoiesis in humans more effectively with less frequent dosing.

Toxicity studies indicated that PEG-IL11 was well tolerated at doses of 0.1-0.3 mg/kg, with only mild to moderate side effects observed, and no additional toxicities from the PEG modification, indicating a promising safety profile for future clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of the mono-PEGylated recombinant human interleukin-11 in cynomolgus monkeys. Yu, KM., Lau, JY., Fok, M., et al.[2018]

Treatment with recombinant Galectin-1 (rGal-1) significantly reduced clinical signs of atopic dermatitis (AD) in a mouse model, indicating its potential as an effective therapeutic option.

rGal-1 treatment led to decreased levels of inflammatory markers such as eotaxin and IL-17, and reduced the infiltration of eosinophils and mast cells, suggesting a mechanism of action that involves modulation of immune responses and skin inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-inflammatory effect of galectin-1 in a murine model of atopic dermatitis. Corrêa, MP., Andrade, FEC., Gimenes, AD., et al.[2019]

In a phase 2a study involving 113 adults with moderate to severe atopic dermatitis, tezepelumab showed a numerically greater efficacy compared to placebo, with 64.7% of patients achieving a ≥50% reduction in eczema severity (EASI50) at week 12.

The safety profile of tezepelumab was comparable to placebo, with similar rates of treatment-emergent adverse events, suggesting it is a safe option for patients when combined with topical corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial. Simpson, EL., Parnes, JR., She, D., et al.[2022]

Recent advances in understanding atopic dermatitis have led to new treatments targeting specific interleukins and using Janus kinase inhibitors to reduce inflammation, which can help many patients.

Despite these breakthroughs, some patients still do not respond to these therapies, indicating that atopic dermatitis has complex underlying causes that vary among different individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunopathogenesis of Atopic Dermatitis: Focus on Interleukins as Disease Drivers and Therapeutic Targets for Novel Treatments. Makowska, K., Nowaczyk, J., Blicharz, L., et al.[2023]

In a phase I study involving 16 children with acute leukaemia, PEG-rhG-CSF was found to be safe for treating chemotherapy-induced neutropenia, with no severe adverse effects like bone pain or nephrotoxicity reported.

The pharmacokinetic analysis showed that the drug's clearance and serum concentration levels were comparable to those seen in other pediatric populations, suggesting its efficacy and potential as a therapeutic option for managing neutropenia in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor in children with acute leukaemia. Liu, XT., Zhao, YX., Jia, GW., et al.[2021]

In a study involving 598 patients with acute lymphoblastic leukemia, PEG-ASP was associated with significantly fewer allergic reactions (13.5%) compared to native L-ASP (41.2%), indicating its improved safety profile.

The presence of anti-PEG-ASP antibodies was linked to faster drug clearance and could predict allergic reactions and rechallenge outcomes, suggesting that monitoring these antibodies may help manage treatment with PEG-ASP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibodies Predict Pegaspargase Allergic Reactions and Failure of Rechallenge. Liu, Y., Smith, CA., Panetta, JC., et al.[2023]

In a study involving 12 patients with IgE-mediated atopic disease, treatment with human IgE pentapeptide (HEPP) resulted in significant improvements in allergy symptom scores, medication usage, and skin test results compared to a placebo.

HEPP was found to be a safe and effective new treatment option for allergic diseases, indicating its potential as a therapeutic modality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of human IgE pentapeptide. Cohen, GA., O'Connor, RD., Hamburger, RN.[2021]

In a study using the NC/Nga mouse model of atopic dermatitis, the combination of FTY720 (Fingolimod) and betamethasone ointment significantly improved dermatitis severity compared to betamethasone alone, indicating enhanced therapeutic efficacy.

FTY720 treatment not only improved skin condition but also reduced key inflammatory markers, such as mast cells and CD3+ T-cells, suggesting a potential mechanism of action that targets underlying inflammation in intractable atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 (fingolimod) in combination with betamethasone ointment in NC/Nga mice]. Tsuji, T., Yoshida, Y., Fujita, T., et al.[2015]

Citations

1. ir.nektar.com ir.nektar.com/news-releases/news-release-details/data-rezolve-ad-phase-2b-study-rezpegaldesleukin-accepted-late

Data from REZOLVE-AD Phase 2b Study for ... Oral Presentation: "Rezpegaldesleukin Novel Treg-Inducing Therapy Demonstrates Efficacy in Atopic Dermatitis and Asthma in Phase 2b Trial" ...

2. ir.nektar.com ir.nektar.com/news-releases/news-release-details/nektar-presents-new-data-rezolve-ad-phase-2b-study

Nektar Presents New Data from REZOLVE-AD Phase 2b ... In the Phase 2b study, rezpegaldesleukin achieved statistical significance on the primary endpoint of mean improvement in Eczema Area and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06136741

NCT06136741 | A Phase 2b Study to Evaluate ... A Phase 2b Study to Evaluate Rezpegaldesleukin (Rezpeg) in the Treatment of Adult Patients With Moderate-to-Severe Atopic Dermatitis (REZOLVE-AD).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11511931/

The regulatory T cell-selective interleukin-2 receptor agonist ... Here, in two phase lb trials, the authors show that rezpegaldesleukin, a Treg-selective pegylated IL-2, is safe and improves symptoms in patients with atopic ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39455575/

The regulatory T cell-selective interleukin-2 receptor ... REZPEG is safe and well-tolerated and demonstrates consistent pharmacokinetics in participants receiving subcutaneous doses of 10 to 12 μg/kg or 24 μg/kg once ...

6. jaad.org jaad.org/article/S0190-9622(25)01903-6/fulltext

65106 Safety profile of Rezpegaldesleukin, A Selective ... This report presents a pooled safety analysis from 9 completed phase 1-2 studies evaluating REZPEG in healthy volunteers and subjects with chronic inflammatory ...

7. ir.nektar.com ir.nektar.com/news-releases/news-release-details/nektar-therapeutics-receives-fast-track-designation

Nektar Therapeutics Receives Fast Track Designation for ... Proof-of-concept efficacy and safety data from a Phase 1b study of rezpegaldesleukin in atopic dermatitis patients were presented at the 2023 ...