Diabetes Autoimmunity Withdrawn In New Onset and In Established Patients

NCT03895437 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: TOL-3021-231
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 23

Brief Summary

The study is a prospective, randomized, 52-week double-blind, placebo-controlled, multicenter trial in subjects with Type 1 diabetes (T1D) followed by a 2-year safety follow-up.

Conditions

Diabetes Mellitus, Type 1

Keywords

Type 1 Diabetes; Diabetes; Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change From Baseline on Log-transformed Mixed Meal Tolerance Test (MMTT) C-peptide Area Under the Curve (AUC)

  The primary outcome is the TOL-3021 treatment effect as determined by a repeated measures analysis of change from baseline in the log-transformed MMTT C-peptide AUC at 12, 16, and 24 weeks

  Baseline,12,16 and 24 weeks

Secondary Outcomes (9)

• Hypoglycemia - % Time Continuous Glucose Monitor (CGM) Reading < 54 mg/dL

  Baseline, Weeks 1-12, Weeks 13-24

• Hypoglycemia -Time CGM < 70 mg/dL

  Baseline, Weeks 1-12, Weeks 13-24

• Severe Hypoglycemic Events Lasting at Least 15 Minutes

  Baseline, Weeks 1-12, Weeks 13-24

• Treatment Effect on Daily Insulin Requirements

  Baseline, Weeks 1-12 and Weeks 13-24

• Effect on Hemoglobin A1c (HbA1c)

  Baseline, 12, 16, 24 weeks

Study Arms (2)

TOL-3021

EXPERIMENTAL

TOL-3021 2 mg/mL

Biological: TOL-3021

TOL-3021 Placebo

PLACEBO COMPARATOR

TOL-3021 Placebo

Other: TOL-3021 Placebo

Interventions

TOL-3021 BIOLOGICAL

TOL-3021 1 mg is a bacterial plasmid expression vector containing the coding sequences for the human proinsulin (hINS) gene.

TOL-3021

TOL-3021 Placebo OTHER

TOL-3021 Placebo

Also known as: Placebo

TOL-3021 Placebo

Eligibility Criteria

• Age: 12 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• Age at randomization of 12.0 - \<41.0 years of age .
• Adequate glycemic control as defined by HbA1c ≤7.9% 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 consecutive or non-consecutive days within 5 days prior to baseline mixed meal tolerance test (MMTT).
• On insulin therapy (total insulin dose \>0.125 U/kg body weight)
• Presence of antibodies to at least one of the following antigens: glutamic acid decarboxylase (GAD65), islet antigen 2 (IA-2), zinc transporter 8 (ZnT8), or insulin if obtained within 10 days of the onset of exogenous insulin therapy, or documentation of positive antibodies. In the absence of a positive result for one of the specified antibodies, diagnosis of T1D as per the ADA guidelines..
• Peak C-peptide during screening 4-hour mixed meal tolerance test (MMTT) ≥ 0.150 nmol/L.
• Willingness to wear the Dexcom G6 continuous glucose monitoring (CGM) device and use according to instructions including recording of total daily insulin dose taken most of each day from screening to end of treatment period.
• Written informed consent and, for subjects aged 12-\<18 years of age, patient assent and parental or guardian consent, including authorization to release health information.
• Willingness and ability of subject to comply with all study procedures of the study protocol, including attending all clinic visits.

You may not qualify if:

• Receiving a dose of acetaminophen \>4,000 mg per day.
• Body Mass Index (BMI) \>32 kg/m² for patients 18 and older (\>85th percentile for ages 12-17)
• Previous immunotherapy for T1D within 2 years of enrollment.
• Diagnosis of liver disease or hepatic enzymes, as defined by alanine aminotransferase (ALT) and/or aspartate aminotransferase (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.) Any underlying conditions likely to impact red blood cell turnover.
• Latent autoimmune diabetes of adults (LADA), which is generally associated with preceding history and treatment of T2D with medications typically used for treatment of type 2 diabetes (T2D) for more than 30 days.
• Monogenic diabetes (MODY).
• Estimated glomerular filtration rate (eGFR) \<60 ml/min for ages 18-\<41, and \<75 ml/min per 1.73 m² for ages 12-\<18.
• 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, unstable 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.
• History of any organ transplant, including islet cell transplant.
• Asthma that requires oral glucocorticoid therapy. Inhaled glucocorticoid therapy is permitted.

Sponsors & Collaborators

• Tolerion, Inc.: lead

Study Sites (23)

Altman Clinical and Translational Research Institute UCSD

San Diego, California, 92093, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Mills-Peninsula Medical Center

San Mateo, California, 94401, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Barbara Davis Center - University of Colorado Denver

Denver, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Baptist Health Research Institute

Jacksonville, Florida, 32258, United States

Location

University of Miami Diabetes Research Institute

Miami, Florida, 33136, United States

Location

University of South Florida Diabetes Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Rocky Mountain Clinical Research

Idaho Falls, Idaho, 83404, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

MedStar Health Research Institute

Baltimore, Maryland, 21239, United States

Location

MedStar Health Research Institute

Hyattsville, Maryland, 20782, United States

Location

Joslin Diabetes Center- Adult & Pediatric

Boston, Massachusetts, 02215, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Naomi Berrie Diabetes Center, Columbia University

New York, New York, 10032, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Mountain Diabetes and Endocrine Center

Asheville, North Carolina, 28803, United States

Location

University of North Carolina Diabetes Care Center

Chapel Hill, North Carolina, 27517, United States

Location

Diabetes and Glandular Disease Clinic, P.A.

San Antonio, Texas, 78229, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Early termination following interim analysis showing lack of efficacy.

Results Point of Contact

• Title: David Glover, Director of Research and Development
• Organization: PBM Capital Group

dglover@pbmcap.com

(434) 980-8154

Study Officials

• Alexander Fleming, M.D.

  Tolerion, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomly assigned to treatment with TOL-3021 or placebo in a 2:1 fashion

Study Record Dates

• First Submitted: March 26, 2019
• First Posted: March 29, 2019
• Study Start: June 17, 2019
• Primary Completion: December 21, 2020
• Study Completion: December 21, 2020
• Last Updated: May 20, 2026
• Results First Posted: May 20, 2026

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (23)