Platform Trial to Delay Stage 3 Diabetes: Comparing Teplizumab With ATG

NCT07216391 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: TN40A
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 2-arm, multi-center, open label study to learn if ATG works the same or better than teplizumab in delaying or preventing Stage 3 Type 1 diabetes. Participants will be administered either 2 infusions of ATG or 14 infusions of teplizumab and will be followed for 12 months after administration.

Conditions

Type 1 Diabetes Mellitus

Keywords

TrialNet; T1D; Teplizumab; ATG

Outcome Measures

Primary Outcomes (1)

• Change in DPTRS at six months

  DPTRS is calculated as DPTRS = (1.569 x log-BMI) - (0.056 x age) + (0.813 x glucose sum from 30 to 120 min /100) - (0.848 x C-peptide sum from 30 to 120 min/10) + (0.476 x log-fasting C-peptide), where the units are years for age, kg/m2 for BMI, mg/dl for glucose, ng/ml for C-peptide

  6 months after completion of study drug administration

Secondary Outcomes (6)

• Progression to Stage 3 T1D

  6 months after study drug administration

• OGTT glucose AUC

  6 months after study drug administration

• M120 score

  6 months after study drug administration

• Index 60

  6 months after study drug administration

• OGTT C-peptide AUC

  6 months after study drug administration

Study Arms (2)

ATG

EXPERIMENTAL

Antithymocyte globulin (ATG) will be intravenously administered over two days, with a total of 2 infusion periods. The first dose (0.5mg/kg) will be infused over a minimum of 6 hours, and the second dose (2mg/kg) over a minimum of 4 hours with a maximum infusion time for each infusion of 10 hours. Infusions may be administered either in a hospital or outpatient setting at the investigator's or institutions discretion.

Drug: Antithymocyte Globulin (ATG)

Teplizumab

ACTIVE COMPARATOR

Intravenous infusions of teplizumab will be given for 14 consecutive days. Each infusion takes about 30 minutes. Vital signs will be monitoring for at least 30 minutes after each infusion. If reactions to the infusion occur participants may be monitored for at least 2 hours after the study drug infusion. The total dose for the 14-day course is approximately 11,240 µg/m².

Drug: Teplizumab

Interventions

Antithymocyte Globulin (ATG) DRUG

Thymoglobulin

ATG

Teplizumab DRUG

Intravenous infusions of teplizumab given for 14 consecutive days. Each infusion takes about 30 minutes and is followed by an observation period of at least 30 minutes.

Teplizumab

Eligibility Criteria

• Age: 4 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 guardians provide informed consent when the participant is \<18 years of age.
• Aged ≥4 to \<35 years
• A history of 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.
• Participants must meet ADA stage 2 T1D glycemic criteria\* by TrialNet testing within 100 days of the baseline visit.
• \*The ADA definition of stage 2 T1D is characterized by glucose intolerance or dysglycemia in the presence of two or more islet autoantibodies, impaired fasting glucose (≥ 100mg/dL), impaired glucose tolerance (2-hour post 75g glucose load ≥ 140mg/dL), high glucose levels at intermediate time points on OGTT (30, 60, 90 min timepoints of ≥ 200 mg/dL), and/or HbA1c between 5.7% and 6.4% or ≥ 10% increase in HbA1c within a two year window, with the most recent HbA1c value obtained within 100 days of the baseline visit.
• CMV and/or EBV seronegative participants must be CMV and EBV PCR negative within 30 days prior to 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 the baseline visit.
• CMV seropositive participants must be CMV PCR negative and all EBV seropositive participants must have EBV PCR \< 2,000 IU/mL within 30 days prior to randomization and may not have had signs or symptoms of a CMV or EBV-compatible illness lasting longer than 7 days within 30 days prior to the baseline visit.
• Be at least 8 weeks from last live immunization at the time of the baseline visit.
• Be willing to forgo vaccines (other than non-live influenza and COVID-19) during the 3 months after study drug treatment period and forgo live vaccines for 12 months after study drug treatment period.
• Must meet TrialNet eligibility minimum immunization recommendations found in Appendix A of the manual of operations (MOO).
• With the exception of stage 2 T1D, participants must be healthy, as defined by absence of any other untreated diagnoses that the investigator deems to be a potential confounder.
• If a female participant with reproductive potential, willing to avoid pregnancy (abstinence or adequate contraceptive method) through the completion of the study infusions and up to 3 months after study drug administration and undergo pregnancy testing prior to each study visit.
• Must be residing or have accommodations within 1 hour of the infusion site during study drug infusions and must be within 1 hour of a medical care facility for 1 day after completion of infusions.
• Participants must live in a location with rapid access to emergency medical services.

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 that 12 g/dL for adult men and less than 11.5g/dL for adult females and less than 11 g/dL for participants under age 18.
• Active signs or symptoms of acute or chronic 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 through any one or more of the following:
• A history of latent or active TB
• Signs and/or symptoms of TB
• Recent close contact with a person with known or suspected active TB unless appropriate prophylaxis for TB was given
• A history of a chest X-ray consistent with active TB or old, inactive TB, or interferon gamma release assay IGRA (QuantiFERON) test
• A history of a positive purified protein derivative (PPD) skin test result (\>10 mm induration), or positive/repeatedly indeterminate on an interferon-gamma release assay (IGRA; e.g., QuantiFERON-TB test).
• Currently pregnant or lactating or anticipate getting pregnant within the study period.
• Require use of other immunosuppressive agents including chronic use of oral or intravenous injectable 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.

Sponsors & Collaborators

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

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Antilymphocyte Serum; teplizumab

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

Central Study Contacts

Melissa Parker

CONTACT

813-396-9378; melissa.parker@epi.usf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: This trial will enroll 60 participants who will be randomly assigned in a 2:1 allocation to the following treatment arms: 40 participants will be randomized to ATG and 20 participants will be randomized to teplizumab.

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: October 14, 2025
• Study Start: April 15, 2026
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): May 30, 2030
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Final datasets will be available at the NIDDK Central Repository 12 months from the last participant's follow-up visit
• Access Criteria: IPD can be requested through the NIDDK Central Repository once submitted.

Locations

US (1)