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