NCT00505375

Brief Summary

The purpose of this study is to determine whether treatment with CTLA4-Ig (Abatacept) in individuals with new onset T1DM will improve insulin secretion (C-peptide production) compared to placebo.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
112

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Feb 2008

Typical duration for phase_2

Geographic Reach
2 countries

13 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 20, 2007

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 23, 2007

Completed
6 months until next milestone

Study Start

First participant enrolled

February 1, 2008

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2012

Completed
4.3 years until next milestone

Results Posted

Study results publicly available

August 16, 2016

Completed
Last Updated

May 6, 2020

Status Verified

April 1, 2020

Enrollment Period

4.2 years

First QC Date

July 20, 2007

Results QC Date

May 12, 2016

Last Update Submit

April 27, 2020

Conditions

Type 1 Diabetes Mellitus

Keywords

CTLA4-IgAbataceptBeta-cell functionT-cellsDPT-1treatmenttreatment of type 1 diabetesnew onset type 1 diabetesjuvenile diabetesT1Ddiabetes mellitusType 1 diabetes TrialNetTrialNet

Outcome Measures

Primary Outcomes (1)

  • Area Under the Stimulated C-peptide Curve Over the First 2 Hours of a 4 Hour Mixed Meal Tolerance Test at the 2 Year Visit

    The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes.

    2 years of follow up

Study Arms (2)

1

EXPERIMENTAL

Intravenous infusions of CTLA-4 Ig

Drug: CTLA-4 Ig

2

PLACEBO COMPARATOR

Intravenous infusions of placebo

Other: Placebo

Interventions

CTLA-4 IgDRUG

Intravenous infusion of 10 mg/kg of CTLA-4 Ig every other week for the first two doses and then every 28 days for a total of 27 doses

Also known as: Abatacept
1
PlaceboOTHER

Intravenous infusions of placebo every other week for the first two doses and then every 28 days for a total of 27 doses

2

Eligibility Criteria

Age6 Years - 45 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Age 6-45
  • Within 3 months (100 days) of diagnosis of T1DM based on ADA criteria
  • At least one diabetes-related autoantibody
  • Stimulated C-peptide level \>0.2 pmol/ml by MMTT conducted 21 days after diagnosis of T1DM and within 37 days of randomization
  • At least three months from last live immunization received and willing to forgo live vaccinations for three months following last dose of study treatment

You may not qualify if:

  • Immunodeficiency, chronic lymphopenia, active infection, positive PPD result or a history of malignancy
  • Serologic evidence of current or past HIV, Hepatitis B or C
  • Pregnancy, lactation, or intention of pregnancy while on study
  • Current use of immunosuppressive agents, or medications known to influence glucose tolerance or glycemic control
  • Current participation in another T1DM treatment study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California - San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

The Barbara Davis Center for Childhood Diabetes

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32610-0296, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Columbia University, Naomi Berrie Diabetes Center

New York, New York, 10032, United States

Location

University of Pittsburgh, Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas, Southwestern Medical School

Dallas, Texas, 75235-8858, United States

Location

Benaroya Research Institute

Seattle, Washington, 98101, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G-1X8, Canada

Location

Related Publications (9)

  • Bach JF. Insulin-dependent diabetes mellitus as an autoimmune disease. Endocr Rev. 1994 Aug;15(4):516-42. doi: 10.1210/edrv-15-4-516.

    PMID: 7988484BACKGROUND

  • Bretscher PA. A two-step, two-signal model for the primary activation of precursor helper T cells. Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):185-90. doi: 10.1073/pnas.96.1.185.

    PMID: 9874793BACKGROUND

  • Alegre ML, Frauwirth KA, Thompson CB. T-cell regulation by CD28 and CTLA-4. Nat Rev Immunol. 2001 Dec;1(3):220-8. doi: 10.1038/35105024.

    PMID: 11905831BACKGROUND

  • Lenschow DJ, Zeng Y, Thistlethwaite JR, Montag A, Brady W, Gibson MG, Linsley PS, Bluestone JA. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg. Science. 1992 Aug 7;257(5071):789-92. doi: 10.1126/science.1323143.

    PMID: 1323143BACKGROUND

  • Abrams JR, Lebwohl MG, Guzzo CA, Jegasothy BV, Goldfarb MT, Goffe BS, Menter A, Lowe NJ, Krueger G, Brown MJ, Weiner RS, Birkhofer MJ, Warner GL, Berry KK, Linsley PS, Krueger JG, Ochs HD, Kelley SL, Kang S. CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J Clin Invest. 1999 May;103(9):1243-52. doi: 10.1172/JCI5857.

    PMID: 10225967BACKGROUND

  • Abrams JR, Kelley SL, Hayes E, Kikuchi T, Brown MJ, Kang S, Lebwohl MG, Guzzo CA, Jegasothy BV, Linsley PS, Krueger JG. Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells. J Exp Med. 2000 Sep 4;192(5):681-94. doi: 10.1084/jem.192.5.681.

    PMID: 10974034BACKGROUND

  • Moreland LW, Alten R, Van den Bosch F, Appelboom T, Leon M, Emery P, Cohen S, Luggen M, Shergy W, Nuamah I, Becker JC. Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis Rheum. 2002 Jun;46(6):1470-9. doi: 10.1002/art.10294.

    PMID: 12115176BACKGROUND

  • 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: 21719096RESULT

  • Orban T, Beam CA, Xu P, Moore K, Jiang Q, Deng J, Muller S, Gottlieb P, Spain L, Peakman M; Type 1 Diabetes TrialNet Abatacept Study Group. Reduction in CD4 central memory T-cell subset in costimulation modulator abatacept-treated patients with recent-onset type 1 diabetes is associated with slower C-peptide decline. Diabetes. 2014 Oct;63(10):3449-57. doi: 10.2337/db14-0047. Epub 2014 May 16.

    PMID: 24834977DERIVED

Related Links

MeSH Terms

Conditions

Diabetes Mellitus, Type 1Diabetes Mellitus

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

ImmunoconjugatesAntibodiesImmunoglobulinsSerum GlobulinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsGlobulins

Results Point of Contact

Title
Carla Greenbaum
Organization
Benaroya Research Institute
cjgreen@benaroyaresearch.org

Study Officials

  • Tihamer Orban, MD

    Joslin Diabetes Center

    PRINCIPAL INVESTIGATOR

  • Jay Skyler, MD

    University of Miami

    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
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 20, 2007

First Posted

July 23, 2007

Study Start

February 1, 2008

Primary Completion

May 1, 2012

Study Completion

May 1, 2012

Last Updated

May 6, 2020

Results First Posted

August 16, 2016

Record last verified: 2020-04

Data Sharing

IPD Sharing
Will share

Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/tn09-ctla4-ig/?query=TN09

More information

Locations

US(12)CA(1)