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Treatment With hOKT3gamma1(Ala-Ala) in T1DM

Primary Purpose

Diabetes Mellitus, Type 1

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

hOKT3gamma1(Ala-Ala)

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Diabetes, juvenile diabetes, teplizumab

Eligibility Criteria

7 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

diagnosed with T1DM within the past 6 weeks
have a body weight ≥26 kg at the time of enrollment
have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days).

Exclusion Criteria:

Pregnant or lactating females;
Prior OKT3 treatment;
Known hypersensitivity to murine products;
Uncompensated heart failure or fluid overload, recent myocardial infarction;
History of epilepsy, cancer, active infection, atopic disease, active Grave's disease, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease, cerebrovascular disease, any concurrent autoimmune diseases, asthma;
Any medical condition that in the opinion of the investigator will interfere with safe completion of the trial;
Inability to give informed consent;
Prior participation in a clinical trial that could potentially affect diabetes or immunologic status;
Participation in a clinical trial within the last 6 weeks;
HIV positive;
Positive for Hepatitis B surface antigen or Anti-Hepatitis C antibody;
Seropositivity for Toxoplasmosis (IgG);
Lymphopenia (<1000 lymphocytes/microliter);
Thrombocytopenia (<150,000/mm3 platelets);
Anemia (Hgb < 10g/dL);
Vaccination with a live virus within the past 6 weeks;
Positive PPD skin test;
Any infectious mononucleosis-like illness within the 3 months prior to enrollment;
Serologic evidence of acute infection with EBV or CMV based on tests listed and as defined by the protocol.

Sites / Locations

University of California San Francisco
Naomie Berrie Diabetes Center, Columbia University
Benaroya Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Treatment

Control

Arm Description

Outcomes

Primary Outcome Measures

4-hour C-peptide AUC

Secondary Outcome Measures

Insulin usage

Full Information

NCT ID

NCT00806572

First Posted

December 9, 2008

Last Updated

February 6, 2017

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Immune Tolerance Network (ITN)

1. Study Identification

Unique Protocol Identification Number

NCT00806572

Brief Title

Treatment With hOKT3gamma1(Ala-Ala) in T1DM

Official Title

Phase II Multiple Dose Treatment of Type 1 Diabetes Mellitus With hOKT3gamma1(Ala-Ala)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Terminated

Why Stopped

Adverse events related to drug lot

Study Start Date

May 2002 (undefined)

Primary Completion Date

July 2004 (Actual)

Study Completion Date

August 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Immune Tolerance Network (ITN)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a phase II study to examine the clinical and immunological effects of humanized FcR non-binding anti-CD3 mAb in participants with Type 1 diabetes mellitus (T1DM), and to develop this therapy to prevent the immune destruction leading to β cell loss.

Detailed Description

This is a 2-arm, open-label phase II trial involving 0 or 3 cycles of treatment 6 months apart with hOKT3γ1 (Ala-Ala), over the first year of disease in participants with new onset T1DM. Each cycle consists of 12 daily doses of hOKT3γ1 (Ala-Ala). Participants will be randomized in a ratio of 2:1 to either the experimental arm or the control arm and will be stratified by study site. To be eligible, participants must be: male or female between 7-30 years of age, diagnosed with T1DM within the past 6 weeks, have a body weight ≥26 kg at the time of enrollment and have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days). Participants randomized to the experimental group will start the first cycle of hOKT3γ1 (Ala-Ala) within 4-8 weeks of T1DM diagnosis. Each participant randomized to the experimental group will receive 3 cycles of drug treatment, separated by 6 months each. Each cycle consists of 12 days of drug treatment. Both groups will undergo the Mixed Meal Stimulated C-Peptide Test and receive blood draws for mechanistic studies on the same schedule.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 1

Keywords

Diabetes, juvenile diabetes, teplizumab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Title

Control

Arm Type

No Intervention

Intervention Type

Drug

Intervention Name(s)

hOKT3gamma1(Ala-Ala)

Other Intervention Name(s)

teplizumab

Intervention Description

3 cycles, six months apart, each consisting of 12 daily infusions with 455-1818ug/m2 hOKT3g1(Ala-Ala)

Primary Outcome Measure Information:

Title

4-hour C-peptide AUC

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Insulin usage

Time Frame

throughout study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

7 Years

Maximum Age & Unit of Time

30 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: diagnosed with T1DM within the past 6 weeks have a body weight ≥26 kg at the time of enrollment have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days). Exclusion Criteria: Pregnant or lactating females; Prior OKT3 treatment; Known hypersensitivity to murine products; Uncompensated heart failure or fluid overload, recent myocardial infarction; History of epilepsy, cancer, active infection, atopic disease, active Grave's disease, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease, cerebrovascular disease, any concurrent autoimmune diseases, asthma; Any medical condition that in the opinion of the investigator will interfere with safe completion of the trial; Inability to give informed consent; Prior participation in a clinical trial that could potentially affect diabetes or immunologic status; Participation in a clinical trial within the last 6 weeks; HIV positive; Positive for Hepatitis B surface antigen or Anti-Hepatitis C antibody; Seropositivity for Toxoplasmosis (IgG); Lymphopenia (<1000 lymphocytes/microliter); Thrombocytopenia (<150,000/mm3 platelets); Anemia (Hgb < 10g/dL); Vaccination with a live virus within the past 6 weeks; Positive PPD skin test; Any infectious mononucleosis-like illness within the 3 months prior to enrollment; Serologic evidence of acute infection with EBV or CMV based on tests listed and as defined by the protocol.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kevan C Herold, MD

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

Naomie Berrie Diabetes Center, Columbia University

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Benaroya Research Institute

City

Seattle

State/Province

Washington

ZIP/Postal Code

98101

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data access is provided to the public in Participant level data and additional relevant materials are available to the public in : 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available.

Citations:

PubMed Identifier

19443276

Citation

Herold KC, Gitelman S, Greenbaum C, Puck J, Hagopian W, Gottlieb P, Sayre P, Bianchine P, Wong E, Seyfert-Margolis V, Bourcier K, Bluestone JA; Immune Tolerance Network ITN007AI Study Group. Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin Immunol. 2009 Aug;132(2):166-73. doi: 10.1016/j.clim.2009.04.007. Epub 2009 May 14.

Results Reference

result

Links:

URL

https://www.niaid.nih.gov/

Description

National Institute of Allergy and Infectious Diseases (NIAID) website

URL

https://www.niaid.nih.gov/about/dait

Description

Division of Allergy, Immunology, and Transplantation (DAIT) website

URL

http://www.immunetolerance.org

Description

Immune Tolerance Network (ITN) website

Available IPD and Supporting Information:

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

http://www.itntrialshare.org/project/Studies/ITN007AIPUBLIC/Study%20Data/begin.view?

Available IPD/Information Identifier

ITN007AI-NDB01

Available IPD/Information Comments

TrialShare is a portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available without charge.Creating an account for ITN TrialShare is free and allows for searching studies of interest.

Available IPD/Information Type

Study protocol synopsis, -navigator, -schedule of events,-data &reports, -specimens et al.

Available IPD/Information URL

http://www.itntrialshare.org/project/Studies/ITN007AIPUBLIC/Study%20Data/begin.view?

Available IPD/Information Identifier

ITN007AI-NDB01

Available IPD/Information Comments

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

http://www.immport.org/immport-open/public/study/study/displayStudyDetail/SDY569

Available IPD/Information Identifier

SDY569

Available IPD/Information Comments

ImmPort study identifier is SDY569. ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts and is available to the Public.

Available IPD/Information Type

Study summary, -design, -medications, -demographics, -lab tests, and -files.

Available IPD/Information URL

http://www.immport.org/immport-open/public/study/study/displayStudyDetail/SDY569

Available IPD/Information Identifier

SDY569

Available IPD/Information Comments

ImmPort study identifier is SDY569. ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts and is available to the Public.

Learn more about this trial

Treatment With hOKT3gamma1(Ala-Ala) in T1DM

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