Diabetes Mellitus, Type 1Phase 2TN28NCT04291703
STOP-T1D Low-Dose (ATG)
A Phase 2 study testing Antithymocyte Globulin in people with Diabetes Mellitus, Type 1, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 22 sites in 2 countries.
Trial 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. This study did not meet enrollment targets and was terminated approximately 13 months after the first participant enrolled. Read more about this study
- Who is it for?
- Ages 6 to 34 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Antithymocyte Globulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 22 sitesin 2 countries
- Study dates
- 1 Nov 2023to 17 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 34 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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):
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- 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
- CMV and/or EBV seronegative participants 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.
- CMV seropositive participants must be CMV PCR negative and all EBV seropositive participants must have EBV PCR < 2,000 IU/mL 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 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).
- Be up to date on all recommended vaccinations based on age of participant*
- With the exception of stage 2 T1D, participants must be healthy, as defined by absence of any other untreated diagnoses that the protocol committee 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 the two days of study drug infusions and must be within 1 hour of a medical care facility for 1 day after completion of infusion 2.
- Participants must live in a location with rapid access to emergency medical services.
- Adult participants must be fully immunized. Pediatric participants who have not completed their primary vaccination schedule must receive all vaccinations allowable per the national/country-specific immunization guidelines for their current age prior to study drug delivery. Any remaining vaccinations should be given and continue per the schedule at least 3 months after study drug is administered. For COVID-19 vaccination, all participants will be strongly encouraged to be up-to-date with COVID-19 vaccine(s) as indicated by country-specific guidelines at least 2 weeks prior to randomization.
Who cannot join
- 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.
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- 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
- Prior treatment with Teplizumab (either in a previous clinical trial or clinically).
- Has participated in a clinical trial for diabetes prevention previously and received active study agent within 3 months of randomization.
- Known allergy to ATG or any product excipient
- Prior treatment with ATG or known allergy to rabbit-derived products or to any product excipient
- Prior adverse reactions to heparin.
- Any condition that in the investigator's opinion may adversely affect study participation will be reviewed by the Study Chair to ensure consistency and adjudicate whether or not the subject may compromise the study results
- Any screening/baseline laboratory result not otherwise stated out of normal reference range and/or medical history that may increase the risk of the subject's participation in this trial.
- Previously diagnosed with Stage 3 TID according to ADA criteria (see Appendix 3 for Criteria for diagnosis of diabetes)
Trial locations and contacts
22 sites in 2 countries.
22 sites in 2 countries
United States20 sites
Emory Children's Center
Atlanta, Georgia, 30322
Barbara Davis Center at University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Florida
Gainesville, Florida, 32610
Prisma Health
Greenville, South Carolina, 29615
Indiana University - Riley Hospital for Children
Indianapolis, Indiana, 46202
Children's Hospital of Iowa
Iowa City, Iowa, 52242
The Children's Mercy Hospital
Kansas City, Missouri, 64108
University of Miami
Miami, Florida, 33136
University of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt Eskind Diabetes Center
Nashville, Tennessee, 37232
Yale University School of Medicine
New Haven, Connecticut, 06511
Columbia University-Naomi Berrie Diabetes Center
New York, New York, 10032
Children's Hospital of Orange County
Orange, California, 92868
University of Pittsburgh
Pittsburgh, Pennsylvania, 15224
University of Utah
Salt Lake City, Utah, 84132
University of California - San Francisco
San Francisco, California, 94143
Benaroya Research Institute
Seattle, Washington, 98101
Stanford University
Stanford, California, 94305
University of South Florida Diabetes Center
Tampa, Florida, 33612
Australia2 sites
Walter and Eliza Hall Institute of Medical Research
Melbourne, Victoria, 3050
Queensland Children's Hospital
South Brisbane, Queensland, 4101
About this study
Official title: Low Dose Antithymocyte Globulin (ATG) to Delay or Prevent Progression to Stage 3 T1D
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. This study did not meet enrollment targets and was terminated approximately 13 months after the first participant enrolled.
Read the detailed description
This study has a planned enrollment period of 4 years and once the enrollment phase has concluded, an additional two years of follow-up visits will be conducted for all participants. Participants enrolled in the first year of the study can expect to complete follow-up visits for approximately four additional years if progression to stage 3 (Type 1 Diabetes Onset) does not occur. Participant follow-up visits after the treatment phase of the study includes general assessments (medical history, physical exam, medications and adverse events) and laboratory assessments to determine current health status and glucose tolerance. This study was terminated early due to lack of enrollment and infeasibility of attaining enrollment goals. Follow-up of enrolled participants continued through study termination, approximately 13 months after the first participant enrolled.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Antithymocyte Globulin, Placebo (for ATG)
- Keywords
- TrialNet, T1D
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antithymocyte GlobulinDrug
Also called Thymoglobulin
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.
Placebo (for ATG)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Antithymocyte globulin (ATG) | Experimental | Participants assigned to this arm will receive ATG Receives: Drug: Antithymocyte Globulin |
| Placebo | Placebo comparator | Participants assigned to this arm will receive saline (placebo) to match ATG infusion Receives: Drug: Placebo (for ATG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression to Stage 3 T1D
The primary outcome is the elapsed time between random treatment assignment and the development of Stage 3 diabetes
Measured: From randomization to study termination, approximately 13 months for the first participant enrolled
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2020
- Study start1 Nov 2023
- Primary completion17 Dec 2024
- Study completion17 Dec 2024
Why it stopped: Study terminated early due to low enrollment and lack of feasibility to meet target enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Michael Haller, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04291703
- Sponsor's protocol ID
- TrialNet TN28
- Other IDs
- UC4DK117009-01
- Acronym
- TN28
- Status last verified
- Jan 2026
- First submitted
- 26 Feb 2020
- Last updated
- 7 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Study was terminated early with only 2 participants enrolled.
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Dose Antithymocyte Globulin (ATG) to Delay or Prevent Progression to Stage 3 T1D
- ClinicalTrials.gov ID
- NCT04291703
- Acronym / sponsor ID
- TN28 / TrialNet TN28
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- TrialNet, T1D
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated early due to low enrollment and lack of feasibility to meet target enrollment.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 1 Nov 2023 (actual)
- Primary completion
- 17 Dec 2024 (actual)
- Study completion
- 17 Dec 2024 (actual)
- First posted
- 2 Mar 2020 (actual)
- Results
- Posted 7 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. This study did not meet enrollment targets and was terminated approximately 13 months after the first participant enrolled.
Detailed description
This study has a planned enrollment period of 4 years and once the enrollment phase has concluded, an additional two years of follow-up visits will be conducted for all participants. Participants enrolled in the first year of the study can expect to complete follow-up visits for approximately four additional years if progression to stage 3 (Type 1 Diabetes Onset) does not occur. Participant follow-up visits after the treatment phase of the study includes general assessments (medical history, physical exam, medications and adverse events) and laboratory assessments to determine current health status and glucose tolerance. This study was terminated early due to lack of enrollment and infeasibility of attaining enrollment goals. Follow-up of enrolled participants continued through study termination, approximately 13 months after the first participant enrolled.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Antithymocyte globulin (ATG) | Experimental | Drug: Antithymocyte GlobulinParticipants assigned to this arm will receive ATG |
| Placebo | Placebo comparator | Drug: Placebo (for ATG)Participants assigned to this arm will receive saline (placebo) to match ATG infusion |
Who may qualify
- Ages
- 6 to 34 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (22 listed)
- 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)
Key exclusion criteria (23 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Antithymocyte GlobulinAlso: ThymoglobulinAntithymocyte 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 (ATG) |
| Placebo (for ATG)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 |
Primary outcome
Progression to Stage 3 T1D
Time frame: From randomization to study termination, approximately 13 months for the first participant enrolled
The primary outcome is the elapsed time between random treatment assignment and the development of Stage 3 diabetes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- TrialNetLink provided by the sponsor.
- Individual participant dataSharing planned: No. Study was terminated early with only 2 participants enrolled.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Haller, MD principal investigator
University of Florida
22 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Antithymocyte Globulin in people with Diabetes Mellitus, Type 1, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 22 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression to Stage 3 T1D (time frame: From randomization to study termination, approximately 13 months for the first participant enrolled). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2026.