Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes

NCT ID: NCT00378508

Last Updated: 2021-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2013-08-31

Brief Summary

This is a randomized placebo controlled study to test whether a single 14 course of treatment with the anti-CD3 monoclonal antibody, hOKT3gamma1(Ala-Ala),Teplizumab will prevent the loss of insulin secretory capacity in individuals with Type 1 diabetes of 4 - 12 months duration since diagnosis.

Detailed Description

The study design is a double blind placebo controlled trial that will enroll subjects between the ages of 8 - 30 who have had the diagnosis of Type 1 diabetes made 4 - 12 months prior to enrollment. A single 14 course of treatment with mAb hOKT3gamma1(Ala-Ala), Teplizumab will be given. The primary endpoint is the C-peptide response to a mixed meal at 12 months. A total of 60 subjects will be enrolled (30 in the drug treatment and 30 in the placebo groups) at 4 study sites: Yale University,the University of California at San Francisco, Children's Hospital of Philadelphia, and the Barbara Davis Diabetes Center.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1

The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.

Group Type: EXPERIMENTAL

mAb hOKT3gamma1(Ala-Ala), Teplizumab

Intervention Type: DRUG

This is a randomized, two-arm, double blind placebo controlled phase II trial in which 60 participants with recent-onset T1DM are randomized at a 1:1 ratio to receive Teplizumab or placebo over a 14 day treatment period. The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2.

2

Normal saline infusion

Group Type: PLACEBO_COMPARATOR

Placebo Arm

Intervention Type: DRUG

Interventions

mAb hOKT3gamma1(Ala-Ala), Teplizumab

This is a randomized, two-arm, double blind placebo controlled phase II trial in which 60 participants with recent-onset T1DM are randomized at a 1:1 ratio to receive Teplizumab or placebo over a 14 day treatment period. The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2.

Intervention Type: DRUG

Placebo Arm

Intervention Type: DRUG

Other Intervention Names

mAb hOKT3gamma1(Ala-Ala), MGA031, Teplizumab

Eligibility Criteria

Inclusion Criteria

• age 8 - 30,
• duration of diabetes 4 - 12 months,
• weight greater than 27.5 kg,
• stimulated C-peptide >= 0.2 pmol/ml

Exclusion Criteria

• asthma,
• history of hepatitis C, hepatitis B, HIV

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kevan C Herold

Role: PRINCIPAL_INVESTIGATOR

Yale University

Jeffrey A Bluestone, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California at San Francisco

Locations

University of California at San Francisco

San Francisco, California, United States

Barbara Davis Diabetes Center

Aurora, Colorado, United States

Yale University

New Haven, Connecticut, United States

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, United States

Countries

United States

References

Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002 May 30;346(22):1692-8. doi: 10.1056/NEJMoa012864.

Reference Type: BACKGROUND

PMID: 12037148 (View on PubMed)

Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005 Jun;54(6):1763-9. doi: 10.2337/diabetes.54.6.1763.

Reference Type: BACKGROUND

PMID: 15919798 (View on PubMed)

Sherr JL, Ghazi T, Wurtz A, Rink L, Herold KC. Characterization of residual beta cell function in long-standing type 1 diabetes. Diabetes Metab Res Rev. 2014 Feb;30(2):154-62. doi: 10.1002/dmrr.2478.

Reference Type: DERIVED

PMID: 24115337 (View on PubMed)

Lebastchi J, Deng S, Lebastchi AH, Beshar I, Gitelman S, Willi S, Gottlieb P, Akirav EM, Bluestone JA, Herold KC. Immune therapy and beta-cell death in type 1 diabetes. Diabetes. 2013 May;62(5):1676-80. doi: 10.2337/db12-1207. Epub 2013 Feb 19.

Reference Type: DERIVED

PMID: 23423576 (View on PubMed)

Herold KC, Gitelman SE, Willi SM, Gottlieb PA, Waldron-Lynch F, Devine L, Sherr J, Rosenthal SM, Adi S, Jalaludin MY, Michels AW, Dziura J, Bluestone JA. Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia. 2013 Feb;56(2):391-400. doi: 10.1007/s00125-012-2753-4. Epub 2012 Oct 21.

Reference Type: DERIVED

PMID: 23086558 (View on PubMed)

Other Identifiers

R01DK057846

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Delay-Study 5

Identifier Type: -

Identifier Source: org_study_id