CTLA4-Ig (Abatacept)for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives At -Risk for Type 1
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|ClinicalTrials.gov Identifier: NCT01773707|
Recruitment Status : Active, not recruiting
First Posted : January 23, 2013
Last Update Posted : April 15, 2022
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The study is a 2-arm, multicenter, 1:1 randomized, placebo controlled clinical trial.
All subjects will receive close monitoring for development of AGT or T1DM. Subjects will receive Abatacept or placebo and close monitoring for development of AGT or T1DM. To assess the safety, efficacy, and mode of action of Abatacept to prevent AGT and T1DM.
The primary objective is to determine whether intervention with Abatacept will prevent or delay the development of AGT in at-risk autoantibody positive non-diabetic relatives of patients with T1DM.
Secondary outcomes include: the effect of Abatacept on the incidence of T1DM; analyses of C-peptide and other measures from the OGTT; safety and tolerability; and mechanistic outcomes.
|Condition or disease||Intervention/treatment||Phase|
|Abnormal Glucose Tolerance Type 1 Diabetes||Drug: CTLA4-Ig (Abatacept) Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||212 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||CTLA4-Ig (Abatacept)for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives At -Risk for Type 1 Diabetes|
|Actual Study Start Date :||March 2013|
|Estimated Primary Completion Date :||November 30, 2022|
|Estimated Study Completion Date :||November 30, 2024|
Experimental: abatacept IV infusion
CTLA4-Ig (Abatacept) will be administered as 14 (30 minute) infusions over one year (3 infusions every other week the first month; monthly for the following 11 months)
Drug: CTLA4-Ig (Abatacept)
Given as 30 minute IV infusion
Other Name: Abatacept
Placebo Comparator: Placebo
The placebo arm will receive 14 (30 minute) IV infusions (containing saline) given 3 times (every other week) the first month and monthly for the following 11 months.
Saline given as 30 minute IV infusion
- Change from Normal Glucose Tolerance to Abnormal Glucose Tolerance [ Time Frame: every six months for 5-6 years ]
Measured by Oral Glucose Tolerance Test (OGTT):
Abnormal Glucose Tolerance is primary endpoint and defined as:
- Fasting plasma glucose ≥ 110 mg/dL (6.1 mmol/L) and < 126 mg/dL (7 mmol/L), or
- 2 hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L) and < 200 (11.1 mmol/L), or
- 30, 60, 90 minute plasma glucose during OGTT ≥ 200 mg/dL (11.1 mmol/L)
- Change in C-peptide response to Oral Glucose Tolerance Test (OGTT) [ Time Frame: Every six months for 5-6 years ]To Determine whether treatment with Abatacept is superior to placebo with respect to C-peptide response to oral glucose tolerance
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||6 Years to 45 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Participant in TrialNet Natural History/Pathway to Prevention Study and thus, a relative of a proband with T1DM.
- Between the ages of 1-45 years at the time of enrollment in TN01 and age ≥ 6 at time of randomization in this trial.
- Willing to provide Informed Consent or have a parent or legal guardian provide informed consent if the subject is <18 years of age.
Normal glucose tolerance by OGTT confirmed 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.
- Fasting plasma glucose < 110 mg/dL (6.1 mmol/L), and
- 2 hour plasma glucose <140 mg/dL (7.8 mmol/L), and
- 30, 60, or 90 minute value on OGTT< 200mg/dL (11.1 mmol/L)
- At least two diabetes-related autoantibodies confirmed to be present on two occasions, not including mIAA. Confirmation of 2 positive autoantibodies must occur within the six months prior to randomization, but the confirmation does not have to involve the same 2 autoantibodies.
- Weight ≥ 20 kg at Baseline Visit.
- If a female participant with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing prior to each infusion.
- At least three months from date of last live immunization.
- Willing to forgo live vaccines while receiving treatment on study and for three months following last study drug administration.
Abnormal Glucose Tolerance or Diabetes
- Fasting plasma glucose ≥ 110 mg/dL (6.1 mmol/L), or
- 2 hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L), or
- 30, 60, 90 minute plasma glucose during OGTT ≥ 200 mg/dL (11.1 mmol/L)
- Insulin autoantibodies (mIAA).
- Are immunodeficient or have clinically significant chronic lymphopenia.
- Have an active infection at time of randomization.
- Have a positive PPD test result or history of previously treated TB, or positive interferon-gamma release assay (IGRA) test.
- Be currently pregnant or lactating, or anticipate getting pregnant within 3 months of the last study drug administration.
- Use of medications known to influence glucose tolerance.
- Require use of other immunosuppressive agents.
- Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B core antibody or surface antigen), or Hepatitis C infection.
- Have serological evidence of current CMV infection.
- Have evidence of active EBV infection.
- 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01773707
|Study Chair:||Carla J Greenbaum, MD||Type 1 Diabetes TrialNet|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|
|Other Study ID Numbers:||
UC4DK106993 ( U.S. NIH Grant/Contract )
UC4DK117009 ( U.S. NIH Grant/Contract )
|First Posted:||January 23, 2013 Key Record Dates|
|Last Update Posted:||April 15, 2022|
|Last Verified:||April 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
prevention of type 1 diabetes
prevention of abnormal glucose tolerance
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Endocrine System Diseases
Immune System Diseases
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs