NCT00378508

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.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
63

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Sep 2006

Longer than P75 for phase_2

Geographic Reach
1 country

4 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

Study Start

First participant enrolled

September 1, 2006

Completed
17 days until next milestone

First Submitted

Initial submission to the registry

September 18, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 20, 2006

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2011

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

October 31, 2012

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2013

Completed
Last Updated

August 13, 2021

Status Verified

August 1, 2021

Enrollment Period

4.9 years

First QC Date

September 18, 2006

Results QC Date

September 4, 2012

Last Update Submit

August 11, 2021

Conditions

Type 1 Diabetes Mellitus

Keywords

immune therapyautoimmunityinsulin secretiondiabetes mellitus

Outcome Measures

Primary Outcomes (2)

  • C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months

    C-peptide secretory response was calculated as ln\[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1\] For presentation, the C-peptide data were converted to the AUC as pmol/ml. This is adjusted for baseline.

    At month 12 post-treatment

  • C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline

    C-peptide secretory response was calculated as ln\[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1\] For presentation, the C-peptide data were converted to the AUC as pmol/ml. This baseline data was used to adjust for the C-peptide AUC primary endpoint measure at 12 months.

    At Baseline (before treatment)

Secondary Outcomes (4)

  • Hemoglobin A1c

    At 12 months post-treatment

  • Average Insulin Use Over 12 Months

    After 12 months post-treatment

  • Baseline Insulin Use

    At baseline (before treatment)

  • Baseline Hemoglobin A1c

    At baseline (before treatment)

Study Arms (2)

1

EXPERIMENTAL

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.

Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab

2

PLACEBO COMPARATOR

Normal saline infusion

Drug: Placebo Arm

Interventions

mAb hOKT3gamma1(Ala-Ala), TeplizumabDRUG

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.

Also known as: mAb hOKT3gamma1(Ala-Ala), MGA031, Teplizumab
1
Placebo ArmDRUG
2

Eligibility Criteria

Age8 Years - 30 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

University of California at San Francisco

San Francisco, California, 94143, United States

Location

Barbara Davis Diabetes Center

Aurora, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 10194, United States

Location

Related Publications (5)

  • 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.

    PMID: 12037148BACKGROUND

  • 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.

    PMID: 15919798BACKGROUND

  • 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.

    PMID: 24115337DERIVED

  • 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.

    PMID: 23423576DERIVED

  • 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.

    PMID: 23086558DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1Autoimmune DiseasesDiabetes Mellitus

Interventions

teplizumab

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesImmune System Diseases

Results Point of Contact

Title
Kevan Herold, MD
Organization
Yale University
kevan.herold@yale.edu
203-785-6507

Study Officials

  • Kevan C Herold

    Yale University

    PRINCIPAL INVESTIGATOR

  • Jeffrey A Bluestone, PhD

    University of California at San Francisco

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

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
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 18, 2006

First Posted

September 20, 2006

Study Start

September 1, 2006

Primary Completion

August 1, 2011

Study Completion

August 1, 2013

Last Updated

August 13, 2021

Results First Posted

October 31, 2012

Record last verified: 2021-08

Locations

US(4)