Preventing Abnormal Glucose Tolerance and Diabetes with an Antibody in Relatives at Risk for the Disease

Phase 1

Conditions: A soluble fusion protein, CTLA-4 Ig, is to be used for the prevention ofabnormal glucose tolerance and diabetes in relatives at risk ofdeveloping the disease.
MedDRA version: 20.1Level: PTClassification code 10066284Term: Diabetes prophylaxisSystem Organ Class: 10042613 - Surgical and medical procedures
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2013-002249-13-FI

Lead Sponsor: TrialNet Coordinating Center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 206

Inclusion Criteria

Study subjects must be or have:
1. Participant in TrialNet Natural History/Pathway to Prevention Study
(TN01) and thus, a relative of a proband with T1DM.
2. Between the ages of 1-45 years at the time of enrollment in TN01 and age = 6 at time of randomization in this trial.
3. Willing to provide Informed Consent or have a parent or legal
guardian provide informed consent the subject is <18 years of age.
4. Normal glucose tolerance by OGTT within 7 weeks (no more than 52
days) of baseline (visit 0). If previous abnormal glucose tolerance, has
had two consecutive OGTTs with normal glucose tolerance.
a. Fasting plasma glucose < 110 mg/dL (6.1 mmol/L), and
b. 2 hour plasma glucose <140 mg/dL (7.8 mmol/L), and
c. 30, 60, or 90 minute value on OGTT< 200mg/dL (11.1 mmol/L)
5. At least two diabetes-related autoantibodies confirmed to be present on two occasions, not including mIAA*. Confirmation of 2 positiveautoantibodies must occur within the six months prior to randomization, but the confirmation does not have to involve the same 2 autoantibodies.
6. Weight = 16 kg at Baseline Visit.
7. If a female participant with reproductive potential (defined as having begun menses), willing to avoid pregnancy during treatment with Abatacept and up to 14 weeks after the last dose and undergo pregnancy testing prior to each infusion.
8. At least three months from date of last live immunization.
9. Willing to forgo live vaccines while receiving treatment on study or within three months following last study drug administration.
Are the trial subjects under 18? yes
Number of subjects for this age range: 103
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 103
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

Potential participants must not meet any of the following exclusion
criteria:
1. Abnormal Glucose Tolerance or Diabetes
a. Fasting plasma glucose = 110 mg/dL (6.1 mmol/L), or
b. 2 hour plasma glucose = 140 mg/dL (7.8 mmol/L), or
c. 30, 60, 90 minute plasma glucose during OGTT = 200 mg/dL (11.1
mmol/L)
2. Insulin autoantibodies (mIAA).
3. Immunodeficient or have clinically significant chronic lymphopenia.
4. Have an active infection at time of randomization.
5. Have a positive PPD test result or history of previously treated TB, or positive interferon-gamma release assay (IGRA) test.
6. Be currently pregnant or lactating, or anticipate getting pregnant within 14 weeks of the last study drug administration.
7. Use of medications known to influence glucose tolerance.
8. Require use of other immunosuppressive agents.
9. Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B core antibody or surface antigen), or Hepatitis C infection.
10. Have serological evidence of current CMV infection.
11. Have evidence of active EBV infection.
12. Have any complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk. These include pre-existing cardiac disease, COPD, neurological, or blood count abnormalities (such as lymphopenia, leukopenia, or thrombocytopenia).
13. Have a history of malignancies.
14. Have Multiple Sclerosis.
15. Have demonstrated allergies to abatacept or any of its excipients (maltose, sodium dihydrogen phosphate monohydrate and sodium chloride).
4. Have an active infection at time of randomization.
5. Have a positive PPD test result or history of previously treated TB, or
positive interferongamma release assay (IGRA) test.
6. Be currently pregnant or lactating, or anticipate getting pregnant
within 3 months of the last study drug administration
7. Use of medications known to influence glucose tolerance.
8. Require use of other immunosuppressive agents.
9. Have serologic evidence of current or past HIV, Hepatitis B (positive
for Hepatitis B core
antibody or surface antigen), or Hepatitis C infection.
10. Have serological evidence of current CMV infection.
11. Have evidence of active EBV infection.
12. Have any complicating medical issues or abnormal clinical laboratory
results that interfere with study conduct or cause increased risk. These
include pre-existing cardiac disease, COPD, neurological, or blood count
abnormalities (such as lymphopenia, leukopenia, or thrombocytopenia).
13. Have a history of malignancies.
14. Have Mulitiple Sclerosis
15. Have demonstrated allergies to abatacept or any of its excipients (maltose, dihydrogen phosphate monohydrate and sodium chloride.)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to determine whether treatment of<br>subjects at risk for diabetes with Abatacept results in delay or<br>prevention of abnormal glucose tolerance.;Secondary Objective: Secondary objectives will determine whether treatment with Abatacept<br>is superior to placebo with respect to the incidence of Type 1 Diabetes<br>Mellitus, determine whether treatment with Abatacept is superior to<br>placebo with respect to C peptide responses to oral glucose, as obtained<br>from timed collections during longitudinal tests, to compare the safety<br>and tolerability of Abatacept to placebo, and to assess the effects of<br>treatment on mechanistic outcomes.;Primary end point(s): The elapsed time from treatment randomisation to the development of<br>abnormal glucose tolerance.;Timepoint(s) of evaluation of this end point: 6 Years

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The elapsed time from the development of abnormal glucose tolerance to<br>the development of type 1 diabetes.;Timepoint(s) of evaluation of this end point: 6 years

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