Diabetes Autoimmunity Withdrawn In New Onset and In Established Patients

Clinical Trial ID: NCT03895437


TThe study is a prospective, randomized, 52-week double-blind, placebo-controlled, multicenter trial in subjects with T1D followed by a 2-year safety follow-up.

The SUNRISE study is a prospective, multi-center, double-blind, randomized, placebo-controlled trial in subjects aged 18.0 to <41.0 years diagnosed with T1D, as defined by American Diabetes Association (ADA) criteria, and within 5 years of diagnosis. Time of diagnosis is defined as the first day of insulin administration. Subjects will be stratified by duration (zero up to 1 year and 1 year up to five years) to ensure balance of disease duration across treatment and placebo groups in each strata. Subjects should be randomized no sooner than 6 weeks after diagnosis, unless blood glucose is adequately controlled for >14 days, defined as 3 consecutive fasting glucose levels by SMBG or lab testing <130 mg/dL. Screening assessments will include a physical examination, an ophthalmic examination, chemistry and hematology safety labs, urinalysis, 24-hour urine protein and creatinine, HbA1c, presence of T1D antibodies, and an MMTT. Approximately 51 qualified subjects who meet all selection criteria will be randomized in a 2:1 ratio to treatment with TOL-3021 or placebo and treated for 52 weeks. Subjects will agree to diabetes management during the study with the goal of maintaining HbA1c levels of approximately 7.0% without frequent episodes of hypoglycemia.


Inclusion Criteria: 1. Diagnosis of Type 1 Diabetes Mellitus based on American Diabetes Association (ADA) criteria and within 5.0 years from diagnosis, defined as the first day of insulin administration. 2. Age at randomization of 18.0 - <41.0 years of age . 3. Adequate glycemic control as defined by HbA1c <7.6% based on point-of-care or local lab measurement and time in glycemic range (70-180 mg/dL) >55% by CGM recording over 3 or more days within 5 days of baseline mixed meal tolerance test (MMTT). 4. On insulin therapy (total insulin dose >0.125 U/kg BW) 5. Presence of antibodies to at least one of the following antigens: GAD-65, IA-2, ZnT8, or insulin, or documentation of positive antibodies. 6. Peak C-peptide during screening 4-hour mixed meal tolerance test (MMTT) ≥ 0.2pmol/mL. 7. Willingness to wear the Dexcom G6 continuous glucose monitoring (CGM) device and use according to instructions most of each day from screening to end of treatment period. 8. Written informed consent, including authorization to release health information. 9. Willingness and ability of subject to comply with all study procedures of the study protocol, including attending all clinic visits. Exclusion Criteria: 1. Body Mass Index (BMI) >32 kg/m2 2. Previous immunotherapy for T1D. 3. Diagnosis of liver disease or hepatic enzymes, as defined by ALT and/or AST ≥ 2.5 times the upper limit of normal (ULN). 4. Hematology: white blood cells (WBC) <3 x 109/L; platelets <100 x 109/L; hemoglobin <10.0 g/dL. (Low WBC values may be repeated every 3-7 days, and results to be discussed with the Medical Monitor.) 5. Latent autoimmune diabetes of adults (LADA), which is generally associated with preceding history and treatment of T2D. 6. Estimated glomerular filtration rate (eGFR) <60 ml/min. 7. History of malignancy, except for cancers in remission >5 years, or basal cell or in situ squamous cell carcinoma of the skin. 8. Significant cardiovascular disease (including inadequately controlled hypertension), history of myocardial infarction, angina, use of anti-anginal medicines (e.g., nitroglycerin), or abnormal stress test, which, in the opinion of the Principal Investigator (PI), would interfere with participation in the trial. 9. Immunosuppressive therapy (systemic corticosteroids, cyclosporine, azathioprine, or biologics) within 30 days of screening. 10. Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, GLP1-RAs, DPP-IV inhibitors, pramlintide, or SGLT-2 inhibitors. 11. Current use of verapamil or α-methyldopa. 12. History of any organ transplant, including islet cell transplant. 13. Asthma that requires oral glucocorticoid therapy. Inhaled glucocorticoid therapy is permitted. 14. Active autoimmune or immune deficiency disorder other than T1D or well-controlled autoimmune conditions (e.g., thyroid disease, celiac disease, and sarcoidosis) Generally excluded conditions include rheumatoid arthritis, moderate-to-severe psoriasis, inflammatory bowel disease, and other autoimmune conditions that may require treatment with TNF or other biologics), unless approved by the Medical Monitor. 15. Thyroid-stimulating hormone (TSH) at screening >7.5 mIU/L. 16. History of adrenal insufficiency. 17. Moderate non-proliferative retinopathy" (NPDR) or proliferative retinopathy 18. Evidence of infection with HBV (as defined by hepatitis B surface antigen, HBsAg), HCV (anti-HCV antibodies), or HIV. 19. Subject is breastfeeding. 20. Positive urine pregnancy test: Females of childbearing potential must be excluded if they have a positive urine pregnancy test at screening or randomization or if they are not using medically acceptable methods of birth control. Acceptable methods of birth control include oral or transdermal contraceptives, condom, spermicidal foam, IUD, progestin implant or injection, abstinence, vaginal ring, or sterilization of partner. The reason for non-childbearing potential, such as bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or 1 year or more postmenopausal must be specified in the subject's Case Report Form (CRF). 21. 21. Males of reproductive potential who are unwilling to use medically acceptable birth control, unless the female partner is postmenopausal or surgically sterile. 22. Any social condition or medical condition that would, in the opinion of the PI, prevent complete participation in the study or would pose a significant hazard to the subject's participation. 23. Anticipated major surgery during the duration of the trial, which could interfere with participation in the trial. 24. History of drug or alcohol dependence within 12 months of screening. 25. Psychiatric disorder that would prevent subjects from giving informed consent. 26. Household members of current participants in this protocol. 27. Subjects who are not fluent in the English language. 28. Participation in other studies involving the administration of an investigational drug or device, including the administration of an experimental agent for T1D, at any time, or use of an experimental device for T1D within 30 days prior to screening, unless approved by the Medical Monitor.

  • Start Date


  • Last Updated


  • Sponsor

    Tolerion, Inc.

  • Condition Name

    Diabetes Mellitus, Type 1

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