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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04291703




Registration number
NCT04291703
Ethics application status
Date submitted
26/02/2020
Date registered
2/03/2020
Date last updated
28/05/2024

Titles & IDs
Public title
STOP-T1D Low-Dose (ATG)
Scientific title
Low Dose Antithymocyte Globulin (ATG) to Delay or Prevent Progression to Stage 3 T1D
Secondary ID [1] 0 0
UC4DK117009
Secondary ID [2] 0 0
TrialNet TN28
Universal Trial Number (UTN)
Trial acronym
TN28
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 1 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Antithymocyte Globulin
Treatment: Drugs - Placebo (for ATG)

Experimental: Antithymocyte globulin (ATG) - 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 Comparator: Placebo - 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.


Treatment: Drugs: Antithymocyte Globulin
Thymoglobulin

Treatment: Drugs: Placebo (for ATG)
Normal Saline administered by IV infusion to mimic ATG
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression to Stage 3 T1D
Timepoint [1] 0 0
5 years

Eligibility
Key inclusion criteria
1. Willing to provide informed consent or have a parent or legal guardian provide
informed consent when the subject is <18 years of age.

2. Age greater than or equal to 6 and < 35 years

3. 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.

4. Weight greater than the 5th percentile for age and sex.

5. BMI < 95th and > 5th percentile for age for those under age 18 years and < 30 and > 15
for adults (= 18)

6. 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

7. 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

8. 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.

9. Be at least 4 weeks from last live immunization

10. 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.

11. Participants must also have a negative COVID-19 test within 7 days of the first day of
treatment if otherwise eligible

12. Willingness to comply with study directed social distancing and protection from
SARS-Cov-2 infection.

13. Be willing to forgo vaccines (other than killed influenza) during the 3 months after
study drug treatment period (Days 0 and 1)

14. Be up to date on all recommended vaccinations based on age of subject*

15. With the exception of stage 2 T1D, subjects must be healthy, as defined by absence of
any other untreated diagnoses that the protocol committee deems to be a potential
confounder.

16. 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.

17. 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.

18. 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.
Minimum age
6 Years
Maximum age
34 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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).

2. 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

3. Active signs or symptoms of acute infection at the time of randomization including
SARS-Cov-2.

4. Uncontrolled autoimmune thyroid disease and/or celiac disease (participants must be
well controlled for the previous 6 months).

5. Evidence of prior or current tuberculosis infection as assessed interferon gamma
release assay (QuantiFERON).

6. Currently pregnant or lactating or anticipate getting pregnant within the study
period.

7. Require use of other immunosuppressive agents including chronic use of systemic
steroids.

8. Evidence of current or past HIV or Hepatitis B or current Hepatitis C infection.

9. 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.

10. A history of malignancies other than of skin.

11. Evidence of liver dysfunction with AST or ALT outside of the reference range.

12. Evidence of renal dysfunction with creatinine outside of the reference range.

13. Increased bilirubin (total and direct) outside of the normal limit (Participants with
documentation of Gilbert's Disease permitted).

14. Vaccination with a live virus within the last 4 weeks.

15. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control
within 7 days of screening

16. Prior treatment with Teplizumab (either in a previous clinical trial or clinically).

17. Has participated in a clinical trial for diabetes prevention previously and received
active study agent within 3 months of randomization.

18. Known allergy to ATG or any product excipient

19. Prior treatment with ATG or known allergy to rabbit-derived products or to any product
excipient

20. Prior adverse reactions to heparin.

21. 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

22. 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.

23. Previously diagnosed with Stage 3 TID according to ADA criteria (see Appendix 3 for
Criteria for diagnosis of diabetes)

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2029
Actual
Sample size
Target
101
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Walter and Eliza Hall Institute of Medical Research - Melbourne
Recruitment postcode(s) [1] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
South Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Government body
Name
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04291703
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Melissa A Parker, MHA
Address 0 0
Country 0 0
Phone 0 0
8133969378
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04291703