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

NCT07142252 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: TN36 Rezpeg in New Onset
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 3

Brief Summary

This Phase 2 study is a 2-arm, multi-center, double-masked (masking of the participant, care provider and investigator), placebo-controlled, 2:1 randomized trial design in new onset T1D participants (within 100 days of diagnosis). Participants will be administered rezpegaldesleukin/placebo once every 14 days over 26 weeks with an additional 6-month follow-up period.

Conditions

Type 1 Diabetes Mellitus

Keywords

TrialNet; T1D

Outcome Measures

Primary Outcomes (1)

• The area under the stimulated C-peptide curve (AUC) Y_MAUC.

  The primary outcome of each participant is the mean area under the stimulated C-peptide curve (AUC) over the 2-hour mixed meal glucose tolerance test conducted at the 12-month visit in nmol/L, denoted as Y\_MAUC.

  12 Months

Secondary Outcomes (6)

• Change of MMTT C-peptide mean AUC

  From enrollment to end of the study at 12 months

• Adverse Events

  From enrollment till the end of the study at 12 months

• Total Daily Insulin Dose per kilogram

  From enrollment and every 3 months to end of study at 12 months.

• Change in Quantitative Response (QR) in placebo and treatment groups over time

  From enrollment to end of treatment at 6 months and end of study at 12 months.

• Change of MMTT Glucose mean AUC

  From enrollment to end of study at 12 months.

Other Outcomes (2)

• Hypersensitivity Events and Urticaria

  30 minutes to up to 12 hours after the start of the hypersensitivity or urticaria event

• Injection Site Reactions

  From enrollment to end of treatment (6 months).

Study Arms (2)

rezpegaldesleukin

EXPERIMENTAL

Participants assigned to this arm will receive Rezpegaldesleukin

Drug: Rezpegaldesleukin

Placebo

PLACEBO COMPARATOR

Participants assigned to this arm will received placebo.

Drug: Placebo

Interventions

Rezpegaldesleukin DRUG

Rezpegaldesleukin will be dosed at 12 μg/kg for subcutaneous injection. Rezpegaldesleukin will be provided as a 1.5 mg/mL sterile solution in a vial for injection preparation. Study agent injections will be administered in the abdomen, back of the upper arm or the upper thigh of the participant.

Also known as: NKTR-358

rezpegaldesleukin

Placebo DRUG

Sterile saline for injection. Placebo will be administered in the same volume and as the active comparator to maintain treatment masking.

Placebo

Eligibility Criteria

• Age: 8 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (3)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Vanderbilt University

Nashville, Tennessee, 37232, United States

NOT YET RECRUITING

University of British Columbia

Vancouver, British Columbia, V5Z4H4, Canada

NOT YET RECRUITING

Related Links

• TrialNet

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Kevan Herold, MD

  Type 1 Diabetes TrialNet Chairman

  STUDY DIRECTOR

• Daniel Moore, MD

  Type 1 Diabetes TrialNet

  STUDY CHAIR

• Megan Levings, PhD

  Type 1 Diabetes TrialNet

  STUDY CHAIR

Central Study Contacts

Jessica Conaty

CONTACT

813-396-9234; Jessica.Conaty@epi.usf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The randomization method will be stratified by TrialNet study site. The participants will not be informed regarding the intervention assignment until the end of the study. The investigator and clinic personnel will also be masked as to study assignment. Laboratories performing assays for this protocol will be masked as to the identity of biological material to be studied.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: This trial will enroll 66 participants who will be randomly assigned in a 2:1 allocation to the following treatment arms: * Approximately 44 participants will be randomized to rezpegaldesleukin * Approximately 22 participants will be randomized to placebo.

Study Record Dates

• First Submitted: August 19, 2025
• First Posted: August 26, 2025
• Study Start: March 25, 2026
• Primary Completion (Estimated): May 25, 2028
• Study Completion (Estimated): May 25, 2028
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Final datasets will be available at the NIDDK Central Repository 12 months from the last participant's follow-up visit
• Access Criteria: IPD can be requested through the NIDDK Central Repository once submitted.

Locations

US (2); CA (1)