A Phase 2b Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of TOL-3021 in Patients With Established Type 1 Diabetes Mellitus

Tolerion, Inc.0 sitesDecember 14, 2019

ConditionsDiabetes Mellitus, Type 1

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Diabetes Mellitus, Type 1
Sponsor: Tolerion, Inc.
Primary Endpoint: Treatment Effect
Status: Withdrawn
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

The study is a prospective, randomized, double-blind, placebo-controlled, multicenter trial in subjects with established T1D.

Detailed Description

The study will include 216 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 18-35 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.

Registry

clinicaltrials.gov

Start Date

December 14, 2019

End Date

December 14, 2023

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Tolerion, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Diagnosis of Type 1 Diabetes Mellitus based on American Diabetes Association (ADA) criteria and within 1.0 to 5.0 years from diagnosis, defined as the first day of insulin administration.
•Adequate glycemic control for \>14 days, defined as 3 consecutive fasting glucose levels by self-administered blood glucose (SMBG) or lab testing \<130 mg/dL.
•Age at randomization of 12.0 - \<18.0 years (adolescent), 18.0 - \<36.0 years of age (adult) .
•HbA1c \<8.5% based on point-of-care or local lab measurement.
•Measurement can be repeated every 5-7 days if \>8.5%.
•Presence of antibodies to at least one of the following antigens: GAD-65, IA-2, ZnT8; or insulin.
•Peak C-peptide during screening 4-hour mixed meal tolerance test (MMTT) ≥ 0.2pmol/mL.
•Willingness to wear a continuous glucose monitoring (CGM) device for specified periods of time.
•Written informed consent, including authorization to release health information and assent for adolescent subjects.
•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

•Body Mass Index (BMI) \>30 kg/m2 for adults; \>95 percentile BMI-for-age for subjects under 18 years of age.
•Previous immunotherapy for T1D.
•Diagnosis of liver disease or hepatic enzymes, as defined by ALT and/or AST ≥ 2.5 times the upper limit of normal (ULN).
•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.)
•Serum creatinine \>1.5 times ULN.
•History of malignancy, except for cancers in remission \>5 years, or basal cell or in situ squamous cell carcinoma of the skin.
•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.
•Immunosuppressive therapy (systemic corticosteroids, cyclosporine, azathioprine, or biologics) within 30 days of screening.
•Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, GLP1-RAs, DPP-IV inhibitors, pramlintide, or SGLT-2 inhibitors.
•Current use of verapamil or α-methyldopa.

Outcomes

Primary Outcomes

Treatment Effect

Time Frame: at Week 52

The primary outcome is the treatment effect on log-transformed MMTT C-peptide area under the curve (AUC) after 52 weeks of TOL-3021 treatment

Secondary Outcomes

Clinical responder analysis(at Week 52)
Other measures of hypoglycemia(at Week 52)
Rate of Clinically important hypoglycemia as defined by measured glucose value of <54 mg/dL (3.0 mM/L)(at Week 52)
Immunologic(at Week 52)