Diabetes Mellitus, Type 1
Conditions
Keywords
Type 1 Diabetes, Diabetes, Diabetes Mellitus
Brief summary
The study is a prospective, randomized, double-blind, placebo-controlled, multi-center trial in subjects with new onset T1D.
Detailed description
The study will include 210 male or female subjects aged 12 to 35 years diagnosed with T1D, as defined by the American Diabetes Association (ADA) criteria and meeting enrollment criteria as follows. Initial enrollment will be restricted to subjects aged 18 and older until an analysis of data from subjects with 3 months' exposure to drug confirms safety. Upon completion of this assessment, enrollment will be open without further restrictions for subjects aged 12-35.
Interventions
OTHERTOL-3021 Placebo
TOL-3021 Placebo
BIOLOGICALTOL-3021
TOL-3021 1 mg is a bacterial plasmid expression vector containing the coding sequences for the human proinsulin (hINS) gene.
Sponsors
Tolerion, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Subjects will be randomly assigned to treatment with TOL-3021 or placebo in a 2:1 fashion
Eligibility
Sex/Gender
ALL
Age
12 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of Type 1 Diabetes Mellitus based on American Diabetes Association (ADA) criteria and ≤100 days since diagnosis, defined as the first day of insulin administration (subjects must be able to be randomized within the 100-day period from diagnosis) . 2. Adequate glycemic control for \>14 days, defined as 3 consecutive fasting glucose levels by self-administered blood glucose (SMBG) or lab testing at \<130 mg/dL. 3. Age at randomization of 12.0 - \<18.0 years (adolescent), 18.0 - \<36.0 years of age (adult) .. 4. HbA1c \<10.0% based on point-of-care or local lab measurement. • Measurement can be repeated every 5-7 days if \>10.0%. 5. Presence of antibodies to at least one of the following antigens: GAD-65, IA-2, ZnT8; or insulin, if obtained within 10 days of the onset of exogenous insulin therapy. 6. Willingness to wear a continuous glucose monitoring (CGM) device for specified periods of time. 7. Written informed consent, including authorization to release health information and assent for adolescent subjects. 8. Willingness and ability of subject or adult guardian to comply with all study procedures of the study protocol, including attending all clinic visits.
Exclusion criteria
1. Body Mass Index (BMI) \>30 kg/m2 for adults; \>95 percentile BMI-for-age for subjects under 18 years of age. 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. Serum creatinine \> 1.5 times ULN. 6. History of malignancy, except for cancers in remission \>5 years, or basal cell or in situ squamous cell carcinoma of the skin. 7. 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. 8. Immunosuppressive therapy (systemic corticosteroids, cyclosporine, azathioprine, or biologics) within 30 days of screening. 9. Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, GLP1-RAs, DPP-IV inhibitors, pramlintide, or SGLT-2 inhibitors. 10. Current use of verapamil or α-methyldopa. 11. History of any organ transplant, including islet cell transplant. 12. Active autoimmune or immune deficiency disorder other than T1D or well-controlled autoimmune thyroid disease (e.g., sarcoidosis, 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. 13. Thyroid-stimulating hormone (TSH) at screening \>2.5 mIU/L. 14. History of adrenal insufficiency. 15. Evidence of infection with HBV (as defined by hepatitis B surface antigen (HBsAg)), HCV (anti-HCV antibodies), or HIV. 16. 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, intrauterine device (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). 17. Males of reproductive potential who are unwilling to use medically acceptable birth control, unless the female partner is postmenopausal or surgically sterile. 18. 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. 19. Anticipated major surgery during the duration of the trial, which could interfere with participation in the trial. 20. History of drug or alcohol dependence within 12 months of screening. 21. Psychiatric disorder that would prevent subjects from giving informed consent. 22. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment effect on log-transformed MMTT C-peptide area under the curve (AUC) | 52 weeks | The primary outcome is the treatment effect on log-transformed MMTT C-peptide area under the curve (AUC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Daily Insulin requirements | 52 weeks | Total daily insulin requirements in units per kilogram (kg) body weight |
| Clinical Responder | 52 weeks | A clinical responder analysis will be undertaken as a secondary endpoint to further characterize the treatment effect on a clinical level. A positive responder outcome will be defined as no change or increase in C-peptide AUC from baseline vs. Week 52 |
| Exogenous insulin-free | at Week 52 | Proportion of subjects in each treatment arm who are exogenous insulin-free for at least 3 months with HbA1c levels less than 6.5% |
| Rate of clinically important hypoglycemia | 52 weeks | glucometer, a single blood glucose level |
| GCM Measurement | at Week 52 | Time in range 70-80 mg/dL |
| Other measures of hypoglycemia | at Week 52 | Severe hypoglycemia (SH) events (impaired or loss of consciousness requiring assistance of another) |
| Immunologic | at Week 52 | Quantum dot (Q-dot) responses within the qualifying subpopulation to confirm induction of specific autoantigen tolerance |
| Persistent Reduction | at Week 52 | Proportion of subjects in each treatment arm who achieve a persistent reduction for at least 3 months in insulin dose to \<0.5 units/kg |
Countries
United States
Outcome results
None listed