CTLA4-Ig (Abatacept)for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives At -Risk for Type 1

NCT01773707 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: Abatacept (IND)UC4DK106993UC4DK117009
• Study Type: interventional
• Target: 212
• Locations: 2 countries
• Sites: 17

Brief Summary

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.

Conditions

Abnormal Glucose Tolerance; Type 1 Diabetes

Keywords

prevention of type 1 diabetes; prevention of abnormal glucose tolerance

Outcome Measures

Primary Outcomes (1)

• Time From Randomization to Confirmed Abnormal Glucose Tolerance Test

  Measured by Oral Glucose Tolerance Test (OGTT): Abnormal Glucose Tolerance is primary endpoint and defined as: 1. Fasting plasma glucose ≥ 110 mg/dL (6.1 mmol/L) and \< 126 mg/dL (7 mmol/L), or 2. 2 hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L) and \< 200 (11.1 mmol/L), or 3. 30, 60, 90 minute plasma glucose during OGTT ≥ 200 mg/dL (11.1 mmol/L)

  96 months

Secondary Outcomes (1)

• Change in C-peptide Concentration to Oral Glucose Tolerance Test (OGTT)

  0 time to 30 months

Study Arms (2)

abatacept IV infusion

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

CTLA4-Ig (Abatacept) DRUG

Given as 30 minute IV infusion

Also known as: Abatacept

abatacept IV infusion

Placebo DRUG

Saline given as 30 minute IV infusion

Placebo

Eligibility Criteria

• Age: 6 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• hour plasma glucose \<140 mg/dL (7.8 mmol/L), and
• , 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.

You may not qualify if:

• Abnormal Glucose Tolerance or Diabetes
• Fasting plasma glucose ≥ 110 mg/dL (6.1 mmol/L), or
• hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L), or
• , 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).

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (17)

University of California - San Francisco

San Francisco, California, 94143, United States

Location

Stanford University Medical Center

Stanford, California, 94305-5208, United States

Location

Barbara Davis Center for Childhood Diabetes, University of Colorado

Denver, Colorado, 80262, United States

Location

Yale Medical School

New Haven, Connecticut, United States

Location

University of Florida

Gainesville, Florida, 32610-, United States

Location

University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University-Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

University of Minnesota

Minneapolis, Minnesota, 57931, United States

Location

Columbia University

New York, New York, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University

Nashville, Tennessee, United States

Location

University of Texas Medical Center at Dallas

Dallas, Texas, 75390-8858, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Benaroya Research Institute at Virginia Mason

Seattle, Washington, 98101, United States

Location

The Hospital for Sick Children

Toronto, Ontario, MSG-1X8, Canada

Location

Related Publications (2)

• Orban T, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, Gottlieb PA, Greenbaum CJ, Marks JB, Monzavi R, Moran A, Raskin P, Rodriguez H, Russell WE, Schatz D, Wherrett D, Wilson DM, Krischer JP, Skyler JS; Type 1 Diabetes TrialNet Abatacept Study Group. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet. 2011 Jul 30;378(9789):412-9. doi: 10.1016/S0140-6736(11)60886-6. Epub 2011 Jun 28.

  PMID: 21719096 BACKGROUND

• Leung SS, Borg DJ, McCarthy DA, Boursalian TE, Cracraft J, Zhuang A, Fotheringham AK, Flemming N, Watkins T, Miles JJ, Groop PH, Scheijen JL, Schalkwijk CG, Steptoe RJ, Radford KJ, Knip M, Forbes JM. Soluble RAGE Prevents Type 1 Diabetes Expanding Functional Regulatory T Cells. Diabetes. 2022 Sep 1;71(9):1994-2008. doi: 10.2337/db22-0177.

  PMID: 35713929 DERIVED

Related Links

• TrialNet

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Abatacept

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)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Results Point of Contact

• Title: Dr. Kevan Herold
• Organization: Yale University

Kevan.Herold@Yale.edu

203-785-6507

Study Officials

• Carla J Greenbaum, MD

  Type 1 Diabetes TrialNet

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2013
• First Posted: January 23, 2013
• Study Start: March 1, 2013
• Primary Completion: December 14, 2021
• Study Completion: December 14, 2022
• Last Updated: June 6, 2024
• Results First Posted: June 6, 2024

Record last verified: 2023-07

Locations

CA (1); US (16)