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

NCT01123083 | Completed Phase 3 Results DMC

• 2 other identifiers: 115494TRX4018
• Study Type: interventional
• Target: 179
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

new onset type 1 diabetes; juvenile diabetes; T1DM; Type 1 diabetes

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in 2 Hour Mixed Meal-stimulated C-peptide Area Under Curve (AUC) (Normalized for 120-minute Time Interval) at Month 12

  C-peptide is a protein that shows how much insulin the body is producing. For 3 days before the mixed meal tolerance test participants were asked to eat a balanced diet. The test was performed only when the finger-stick blood glucose level was above 70 mg per deciliter (mg/dL) and no higher than 200 mg/dL. Mixed meal-stimulated C-peptide AUC was the area under the C-peptide/time curve from time 0 to 120-minutes, calculated using the trapezoidal rule. This AUC was normalized for time interval by dividing it by 120-minutes (the number of minutes over which it was determined), and was adjusted by inclusion of Baseline C-peptide AUC as a covariate in the analysis. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the value at Month 12 from the Baseline value.

  Baseline (Day 1) and Month 12

Secondary Outcomes (9)

• Change From Baseline in 2 Hour Mixed Meal-stimulated C-peptide AUC (Normalized for 120-minute Time Interval) at Week 12 and 6 Months

  Baseline (Day 1) and Week 12, Month 6

• Change From Baseline in Stimulated C-Peptide Mean AUC at Week 12, Month 6, 12 and 18

  Baseline (Day 1) and Week 12, Month 6, 12, 18

• Number of Participants With Responder Status

  Month 3, 6 and 12

• Change From Baseline in Mean Daily Insulin Use Over 7 Consecutive Days During the 2 Weeks Prior to the Assessment

  Baseline (Day 1) and Month 3, 6, 12

• Change From Baseline in HbA1c Levels Over 7 Consecutive Days During the 2 Weeks Prior to the Assessment

  Baseline (Day 1) and Month 3, 6, 12

Study Arms (2)

otelixizumab

EXPERIMENTAL

otelixizumab

Biological: Otelixizumab

placebo

PLACEBO COMPARATOR

placebo

Biological: Placebo

Interventions

Otelixizumab BIOLOGICAL

infusion

Also known as: ChAglyCD3, TRX4, monoclonal antibody, anti-CD3

otelixizumab

Placebo BIOLOGICAL

Infusion

placebo

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

GSK Investigational Site

Roma, 00155, Italy

Location

Related Publications (3)

• 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.

  PMID: 15972866 BACKGROUND

• 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.

  PMID: 20225393 BACKGROUND

• 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.

  PMID: 19111162 BACKGROUND

Related Links

• Website containing information regarding the DEFEND-2 trial

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

otelixizumab; Antibodies, Monoclonal; Muromonab-CD3

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Immunoglobulin G; Immunoglobulin Isotypes

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2010
• First Posted: May 14, 2010
• Study Start: May 17, 2010
• Primary Completion: March 9, 2012
• Study Completion: March 9, 2012
• Last Updated: September 15, 2017
• Results First Posted: September 15, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

IT (1)