Trial of Otelixizumab for Adolescents and Adults With Newly Diagnosed Type 1 Diabetes Mellitus (Autoimmune): DEFEND-2

NCT ID: NCT01123083

Last Updated: 2017-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 179 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-17
• Study Completion Date: 2012-03-09

Brief Summary

DEFEND-2 is a Phase 3 confirmatory study for the Phase 3 DEFEND-1 study. The study objective is to find out if an 8-day series of otelixizumab infusions leads to greater improvement in insulin secretion as compared with placebo. Insulin secretion will be assessed using mixed meal-stimulated C-peptide.

Subjects will be assigned to receive either otelixizumab or placebo at a ratio of 2:1 (2/3 otelixizumab, 1/3 placebo). These study agents will be administered as an addition to insulin, diet, and other standard of care treatments.

Detailed Description

The following visits are required:

• Screening Visits: 2 to 3 appointments will be conducted to determine eligibility. At 2 of these visits participants will drink a liquid meal and have blood tests done over the post-meal period. Participants will also be required to wear a continuous glucose monitor for a short period of time.
• Dosing Visits: 8 outpatient visits on consecutive days, each lasting about 2-4 hours.
• Follow-up Visits: weekly for the first month, then every 2 weeks for 3 months, followed by monthly visits through 1 year. There will be 3 visits in the second year.
• The total duration of the study is 2 years.
• Glucose test strips and glucose monitors will be provided to participants for the duration of the study. Frequent glycemic monitoring will occur through lab testing and blood glucose self-monitoring to help facilitate tight glycemic control in all subjects. Subjects will be asked to intermittently record their insulin doses using a telephone or web based system and continuous glucose monitoring will be performed every 6 months.

Conditions

Diabetes Mellitus, Type 1

Study Design

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

Study Groups

otelixizumab

otelixizumab

Group Type: EXPERIMENTAL

Otelixizumab

Intervention Type: BIOLOGICAL

infusion

placebo

placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Infusion

Interventions

Otelixizumab

infusion

Intervention Type: BIOLOGICAL

Placebo

Infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

ChAglyCD3; TRX4; monoclonal antibody; anti-CD3

Eligibility Criteria

Inclusion Criteria

• Ages 12-17
• Diagnosis of diabetes mellitus, consistent with ADA criteria
• No more than 90 days between diagnosis and administration of study compounds
• Requires insulin for type 1 diabetes mellitus, or has required insulin at some time between diagnosis and administration of study compounds. In Canada, has to be using insulin at the time of dosing.
• Stimulated C-peptide level greater than 0.20 nmol/L and less than or equal to 3.50 nmol/L
• Positive for one or more of the autoantibodies typically associated with T1DM: antibody to glutamic acid decarboxylase (anti-GAD); antibody to protein tyrosine phosphatase-like protein (anti-IA-2); zinc transporter autoantibodies (ZNT8); insulin autoantibodies (IAA). A subject who is positive for insulin autoantibodies (IAA) and negative for the other autoantibodies will only be eligible if the subject has used insulin for less than 7 days total.

Exclusion Criteria

•Other, significant medical conditions based on the study doctor's evaluation

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Roma, , Italy

Countries

Italy

References

Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G, Gorus F, Goldman M, Walter M, Candon S, Schandene L, Crenier L, De Block C, Seigneurin JM, De Pauw P, Pierard D, Weets I, Rebello P, Bird P, Berrie E, Frewin M, Waldmann H, Bach JF, Pipeleers D, Chatenoud L. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med. 2005 Jun 23;352(25):2598-608. doi: 10.1056/NEJMoa043980.

Reference Type: BACKGROUND

PMID: 15972866 (View on PubMed)

Keymeulen B, Walter M, Mathieu C, Kaufman L, Gorus F, Hilbrands R, Vandemeulebroucke E, Van de Velde U, Crenier L, De Block C, Candon S, Waldmann H, Ziegler AG, Chatenoud L, Pipeleers D. Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell mass. Diabetologia. 2010 Apr;53(4):614-23. doi: 10.1007/s00125-009-1644-9. Epub 2010 Jan 14.

Reference Type: BACKGROUND

PMID: 20225393 (View on PubMed)

You S, Candon S, Kuhn C, Bach JF, Chatenoud L. CD3 antibodies as unique tools to restore self-tolerance in established autoimmunity their mode of action and clinical application in type 1 diabetes. Adv Immunol. 2008;100:13-37. doi: 10.1016/S0065-2776(08)00802-X. No abstract available.

Reference Type: BACKGROUND

PMID: 19111162 (View on PubMed)

Study Documents

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

http://www.defendagainstdiabetes.com

Website containing information regarding the DEFEND-2 trial

Other Identifiers

TRX4018

Identifier Type: OTHER

Identifier Source: secondary_id

115494

Identifier Type: -

Identifier Source: org_study_id