Rezpegaldesleukin (Nktr-358) in New Onset Type 1 Diabetes Mellitus

Study on Investigational Medication for Onset Type 1 Diabetes

L
Linda DiMeglio, MD

Primary Investigator

Enrolling By Invitation
8 years - 45 years
All
Phase 2
1 participants needed
3 Locations

Brief description of study

This Phase 2 study is a 2-arm, multi-center, double-masked, placebo-controlled, 2:1 randomized sequential trial design in new onset T1D participants (within 100 days of diagnosis). 

THIS STUDY IS ENROLLING BY INVITATION ONLY 

Detailed description of study

This protocol will enroll 66 participants within 100 days of T1D diagnosis who will be treated with either rezpegaldesleukin or placebo with subcutaneous injections over 26 weeks, administered once every 14 days. 

The rezpegaldesleukin/placebo treatment will be administered at the study site. Mixed meal tolerance testing will be done at the screening, baseline visit (V0) and at 3, 6 and 12 months during the study. 

Once the 26-week treatment period has been completed, participants will continue follow-up visits until 12 months from the baseline visit.

Participants will be administered rezpegaldesleukin/placebo once every 14 days over 26 weeks with an additional 6-month follow-up period.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Type 1 Diabetes Mellitus, Riley
  • Age: 8 years - 45 years
  • Gender: All

Inclusion Criteria:

  • Provide informed consent or assent as appropriate and if < 18 years of age have a parent or legal guardian provide informed consent.
  • Age ≥ 8 and ≤ 45 years at the time of signing informed consent and (as applicable) assent A.
  • Diagnosis of T1D within 100 days of randomization.
  • Positive for at least one islet cell autoantibody; GAD65A, mIAA (if obtained within 10 days of the onset of insulin therapy), IA-2A, ICA, or ZnT8A.
  • Stimulated C-peptide of ≥ 0.2 pmol/mL measured during MMTT conducted at least 21 days from diagnosis of diabetes.
  • Participants ≥ 18 years old to have body weight ≥ 35 kg and ≤ 130kg.
  • Participants < 18 years old to have body weight > 5th and <98th percentile for age and sex.
  • Willing to comply with intensive diabetes management.
  • All CMV and/or EBV seronegative participants must be CMV and EBV PCR negative within 30 days of randomization and may not have had signs or symptoms of a CMV or EBV-compatible illness lasting longer than 7 days within 30 days of randomization.
  • All CMV seropositive participants must be CMV PCR negative and all EBV seropositive participants must have a EBV PCR viral load < 2,000 IU/mL within 30 days of randomization. All participants may not have had signs or symptoms of a CMV or EBV-compatible illness lasting longer than 7 days within 30 days of randomization.
  • Must meet "TrialNet Eligibility Minimum Immunization Recommendations" found in Appendix A of the MOO B.
  • Be at least 4 weeks from last live vaccination prior to randomization.
  • Participants that are not already immunized against the current year's influenza are required to receive non-live influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available.
  • Be willing to forgo vaccines (other than killed influenza and COVID-19) during the treatment phase and the 3 months after study drug treatment period.
  • If a female participant with reproductive potential, must be willing to avoid pregnancy (abstinence or highly effective contraceptive method) through the completion of the study and undergo pregnancy testing prior to each study visit.
  • Males of reproductive age must use an adequate contraceptive method during the treatment phase and for 3 months following the last dose of study drug.

A Only adult participants ≥ 18 years old are permitted to be included in the first 18 enrolled participants in this study. Participants ≥ 12 and < 18 years of age are only permitted to screen for this study if the safety review of the first 18 adult participants is assessed favorably by the TrialNet DSMB in consultation with Nektar Safety Group. Once an additional 17 participants ages 12 to 45, including at least 9 participants aged 12-17, enroll and complete through the 6-month visit and have the safety review assessed favorably by the TrialNet DSMB in consultation with Nektar Safety Group, then the trial is permitted to screen and enroll the remaining 31 enrollees ≥ 8 and ≤ 45 years old. If data at either juncture do not support expansion into the pediatric ages, the trial will enroll the remaining participants to reach the target sample size with the currently approved age thresholds. See protocol sections 2.5 and 3.5 for additional details.

B For COVID-19 vaccination and HPV vaccination, all participants will be strongly encouraged to be up to date with COVID-19 vaccine(s) as indicated by country-specific guidelines and HPV vaccine(s) at least 2 weeks prior to randomization.

Exclusion Criteria:

  • One or more screening laboratory values as stated
    • Neutrophils < 1,500 /μL
    • Lymphocytes < 800 /μL
    • Platelets < 100,000 /μL
    • Hemoglobin < 6.2 mmol/L (10.0 g/dL)
    • Eosinophils > 1,000 /μL
    • Potassium > 5.5 mmol/L or < 3.0 mmol/L
    • Sodium > 150 mmol/L or < 130 mmol/L
    • Estimated Glomerular Filtration Rate (eGFR) < 60 mL/min/1.73m2
    • AST or ALT or ALP > 2 times the upper limit of normal based on lab reference range
    • Total Bilirubin ≥ 1.5 times upper limit of normal unless diagnosed with Gilbert's syndrome
    • Serum creatinine > 2 times the upper limit of normal
  • Current or ongoing use of non-insulin pharmaceuticals that affect glycemia within 7 days of the screening visit or any prohibited concomitant medication as listed in section 3.7.
  • Concurrent treatment with systemic immunosuppressive agents (including biologics or steroids) - intranasal and inhaled corticosteroids are permitted as well as eye and ear drops containing corticosteroids.
  • Have active signs or symptoms of acute infection at the time of randomization.
  • Active acute or chronic infection requiring medical treatment (antibiotics, antiviral, antifungal) within 4 weeks of baseline visit unless approved by the Infectious Disease Committee.
  • Have evidence of prior or current tuberculosis infection as assessed by Purified Protein Derivative (PPD), interferon gamma release assay (IGRA) or by history.
  • Any present malignancies or history of malignancy within the past 5 years, other than a successfully treated nonmelanoma skin cancer.
  • Be currently pregnant or lactating or anticipate becoming pregnant during the study.
  • History of severe cardiac disease (i.e. myocardial infarction, unstable ischemic heart disease, cerebrovascular accident, stroke, stage 3 or 4 heart failure).
  • Have evidence of current or past HIV or Hepatitis B infection.
  • Have evidence of active Hepatitis C infection.
  • History of organ allograft.
  • Hypersensitivity to IL-2, PEG, or any components of the active drug.
  • Had major surgery within 12 weeks before the screening visit or anticipates requiring major surgery during the study.
  • Has any autoimmune disease other than T1D, stable thyroid, stable asthma, inactive Graves' disease or celiac disease (e.g., rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematous) or has any other disease that may be affected by immunotherapy.
  • Prior treatment within 12 months of randomization with an immune modulating/immune depleting agents, such as teplizumab (TZield), thymoglobulin (ATG) or rituximab.
  • Prior treatment within 6 months of randomization with a metabolic therapy intended to alter the disease course of T1D (e.g. teplizumab).
  • Has significant and uncontrolled disease/condition in the investigator's opinion that may adversely affect study participation or may compromise the study results or increase participant risk.

This study investigates an investigational medication for people with new onset Type 1 diabetes. Type 1 diabetes is a chronic disease where the body's defense system mistakenly attacks specific cells within the pancreas, which make insulin. Insulin helps control sugar in the blood. When these cells are damaged, they cannot make enough insulin. This means people with Type 1 diabetes need to take insulin every day to keep their blood sugar at safe levels. This study has two arms: one group receives the investigational medication, and the other receives a placebo, which is an inactive substance that looks like the investigational medicine but does not contain any medicine.

Participants in the study will receive injections every 14 days for 26 weeks. The injections will be administered at the study site. During the study, participants will undergo mixed meal tolerance testing at the start and at 3, 6, and 12 months. After the 26-week treatment period, participants will continue with follow-up visits until 12 months from the baseline visit.

  • Who can participate: Participants aged 8 to 45 years diagnosed with Type 1 diabetes within the last 100 days can join. They must be positive for at least one islet cell autoantibody and meet specific health criteria.
  • Study details: Participants will receive either the investigational medication or a placebo. They will receive injections every 14 days over a period of 26 weeks, followed by a 6-month follow-up period.
Updated on 06 Jul 2026. Study ID: PENDO-NIDDK-TN-36-RESET, 30242
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Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting Referrals by Invitation Only