STOP-T1D Low-Dose (ATG)

NCT04291703 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: TrialNet TN28UC4DK117009-01
• Study Type: interventional
• Target: 2
• Locations: 2 countries
• Sites: 22

Brief Summary

A multi-center, placebo-controlled, double blind, 2:1 randomized control clinical trial testing low-dose ATG vs. placebo in subjects with a 2 year 50% risk of progression to stage 3 T1D.

Conditions

Diabetes Mellitus, Type 1

Keywords

TrialNet; T1D

Outcome Measures

Primary Outcomes (1)

• Progression to Stage 3 T1D

  The primary outcome is the elapsed time from random treatment assignment to the development of diabetes or time of last contact among those randomized

  5 years

Study Arms (2)

Antithymocyte globulin (ATG)

EXPERIMENTAL

Antithymocyte globulin (ATG) will be intravenously administered over two days, with a total of 2 infusion periods. The first infusion is given at baseline visit (day 1), the second is given the next day at baseline visit (day 2). Body weight at baseline (Day 0- admission for the ATG/placebo infusion) will be used in calculating the doses for all infusions. The first dose (0.5mg/kg) will be infused over a minimum of 4 hours, and the second dose (2mg/kg) over a minimum of 4 hours with a maximum infusion time for each infusion of 10 hours. The second dose should be given no less than 12 and no more than 30 hours from the start of the first infusion. The final prepared product is to be labeled to protect the blind. Infusions may be administered either in a hospital or outpatient setting at the investigator's or institutions discretion.

Drug: Antithymocyte Globulin

Placebo

PLACEBO COMPARATOR

0.9% Sodium Chloride Injection USP ("Normal" saline) is to be dispensed as the placebo for this study. The placebo is to be prepared dispensing an infusion bag of 0.9% Sodium Chloride Injection USP ("Normal" saline) with no additives (no ATG, no premedications) and label the product to protect the blind. The placebo will also be administered over a minimum of 4 hours for the first and second doses with a maximum infusion time of 10 hours. The second dose of the placebo arm should be given no less than 12 and no more than 30 hours from the start of the first infusion. Infusions may be administered either in a hospital or outpatient setting at the investigator's or institutions discretion.

Drug: Placebo (for ATG)

Interventions

Antithymocyte Globulin DRUG

Thymoglobulin

Also known as: Thymoglobulin

Antithymocyte globulin (ATG)

Placebo (for ATG) DRUG

Normal Saline administered by IV infusion to mimic ATG

Placebo

Eligibility Criteria

• Age: 6 Years - 34 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Willing to provide informed consent or have a parent or legal guardian provide informed consent when the subject is \<18 years of age.
• Age greater than or equal to 6 and \< 35 years
• At least two or more diabetes-related biochemical autoantibodies (mIAA, GADA, ICA, IA-2A, ZnT8A) present on the same sample. In the absence of other antibodies, ICA and GADA positivity alone will not suffice for eligibility in this trial.
• Weight greater than the 5th percentile for age and sex.
• BMI \< 95th and \> 5th percentile for age for those under age 18 years and \< 30 and \> 15 for adults (≥ 18)
• ADA Stage 2 criteria\* AND at least one of the following high-risk markers (occurring at the same visit) within 7 weeks (52 days) of randomization, defined below (for defining a 2-year 50% risk for progression to Stage 3 T1D):
• a. HbA1c ≥ 5.7 and \<6.5% b. Index60 ≥ 1.4 i. Index60 = 0.3695 × (log fasting C-peptide \[ng/mL\]) + 0.0165 × 60-min glucose (mg/dL) - 0.3644 × 60-min C-peptide (ng/mL) c. DPTRS ≥ 7.4 DPTRS = (1.57 x log BMI) - (0.06 x age) + (0.81 x glucose sum from 30 to 120 min/100) - (0.85 x C-peptide sum from 30 to 120 min/10) + (0.48 x log fasting C-peptide)
• \*Dysglycemia is defined as 2-hr glucose ≥ 140 and \<200 mg/dL or fasting glucose ≥ 110 and \<126 or 30, 60, or 90 minute glucose ≥ 200 mg/dL from OGTT
• All subjects 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
• Seated blood pressure less than 130/80 mmHg for participants ≥ 18 years. For participants \< 18 years seated blood pressure less than 95th percentile for age, sex and height.
• Be at least 4 weeks from last live immunization
• Participants 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.
• Participants must also have a negative COVID-19 test within 7 days of the first day of treatment if otherwise eligible
• Willingness to comply with study directed social distancing and protection from SARS-Cov-2 infection.
• Be willing to forgo vaccines (other than killed influenza) during the 3 months after study drug treatment period (Days 0 and 1)

You may not qualify if:

• Immunodeficiency or clinically significant chronic lymphopenia: (Leukopenia (\< 3,000 leukocytes /μL), neutropenia (\<1,500 neutrophils/μL), lymphopenia (\<800 lymphocytes/μL), thrombocytopenia (\<100,000 platelets/μL).
• Hemoglobin less than 13.5 g/dL for adult men and less than 12 g/dL for adult females and less than 11 g/dL for participants under age 18
• Active signs or symptoms of acute infection at the time of randomization including SARS-Cov-2.
• Uncontrolled autoimmune thyroid disease and/or celiac disease (participants must be well controlled for the previous 6 months).
• Evidence of prior or current tuberculosis infection as assessed interferon gamma release assay (QuantiFERON).
• Currently pregnant or lactating or anticipate getting pregnant within the study period.
• Require use of other immunosuppressive agents including chronic use of systemic steroids.
• Evidence of current or past HIV or Hepatitis B or current Hepatitis C infection.
• Any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk to include pre-existing cardiac disease, COPD, sickle cell disease, neurological disease, or blood count abnormalities.
• A history of malignancies other than of skin.
• Evidence of liver dysfunction with AST or ALT outside of the reference range.
• Evidence of renal dysfunction with creatinine outside of the reference range.
• Increased bilirubin (total and direct) outside of the normal limit (Participants with documentation of Gilbert's Disease permitted).
• Vaccination with a live virus within the last 4 weeks.
• Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within 7 days of screening

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (22)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

University of California - San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Barbara Davis Center at University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06511, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of South Florida Diabetes Center

Tampa, Florida, 33612, United States

Location

Emory Children's Center

Atlanta, Georgia, 30322, United States

Location

Indiana University - Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Children's Hospital of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

The Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Columbia University-Naomi Berrie Diabetes Center

New York, New York, 10032, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Prisma Health

Greenville, South Carolina, 29615, United States

Location

Vanderbilt Eskind Diabetes Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Benaroya Research Institute

Seattle, Washington, 98101, United States

Location

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

Walter and Eliza Hall Institute of Medical Research

Melbourne, Victoria, 3050, Australia

Location

Related Links

• TrialNet

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Antilymphocyte Serum; thymoglobulin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The randomization method will be stratified by TrialNet study site. The participants will not be informed regarding the intervention assignment until the end of the study. The investigator and clinic personnel will also be masked as to study assignment. Laboratories performing assays for this protocol will be masked as to the identity of biological material to be studied.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Eligible study participants will be randomized in a 2:1 allocation to either ATG vs. placebo treatment arms by the TrialNet Coordinating Center at the baseline visit once eligibility has been confirmed. Randomization will be conducted using block randomization with variable block sizes with stratification on TrialNet study site and age group (\< 12 years old vs. 12 years old or older). Subjects will be assigned a study randomization number corresponding to the treatment group assignment.

Study Record Dates

• First Submitted: February 26, 2020
• First Posted: March 2, 2020
• Study Start: November 1, 2023
• Primary Completion: December 17, 2024
• Study Completion: December 17, 2024
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); US (20)