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

NCT00678886 | Completed Phase 3 Results DMC

• 2 other identifiers: 115495TRX4006
• Study Type: interventional
• Target: 272
• Locations: 9 countries
• Sites: 109

Brief Summary

The purpose of this study is to find out if an 8-day series of otelixizumab infusions leads to greater improvement in insulin secretion as compared with placebo infusion. 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 physician determined standard of care treatments. DEFEND-1 is now closed to enrollment. DEFEND-2 will begin early in 2010. It is very similar to DEFEND-1 and will again require subjects with new onset type 1 diabetes. Please check back here for more details. In the meantime, established and new onset type 1 diabetes patients in North America are welcome to consider the TTEDD study: http://www.clinicaltrials.gov/ct2/show/NCT00451321?term=TTEDD\&rank=1

Conditions

Diabetes Mellitus, Type 1

Keywords

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

  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 reported AUC was normalized for time interval by dividing it by 120 minutes. This normalized AUC was calculated for each participant at Baseline, Week 12, and at Months 6, 12, 18, and 24. Data has been presented for meal stimulated C-peptide Area under assessment performed at Month 12. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Month 12.

  Baseline (0-120 minutes on Day 1) and Month 12 (0-120 minutes)

Secondary Outcomes (19)

• Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12

  Week 12 and Months 6 and 12

• Mean Daily Insulin Use at Week 12 and Months 6 and 12.

  Week 12 and Months 6 and 12.

• HbA1c Level at Week 12 and Months 6 and 12

  Week 12 and Months 6 and 12

• Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12

  Upto Month 12

• Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12

  Upto Month 12

Study Arms (2)

otelixizumab

EXPERIMENTAL

otelixizumab

Biological: otelixizumab infusion plus physician determined standard of care

placebo

PLACEBO COMPARATOR

Placebo

Biological: placebo infusion plus physician determined standard of care

Interventions

otelixizumab infusion plus physician determined standard of care BIOLOGICAL

infusion

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

otelixizumab

placebo infusion plus physician determined standard of care BIOLOGICAL

infusion

placebo

Eligibility Criteria

• Age: 12 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Ages 12-45
• 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.
• 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 (109)

GSK Investigational Site

Birmingham, Alabama, 35294, United States

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GSK Investigational Site

Little Rock, Arkansas, 72205, United States

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GSK Investigational Site

Costa Mesa, California, 92626, United States

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GSK Investigational Site

Los Angeles, California, 90033, United States

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GSK Investigational Site

Orange, California, 92868, United States

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GSK Investigational Site

Riverside, California, 92506, United States

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GSK Investigational Site

Santa Ana, California, 92705, United States

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GSK Investigational Site

Torrance, California, 90502, United States

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GSK Investigational Site

Walnut Creek, California, 94598, United States

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GSK Investigational Site

Aurora, Colorado, 80045, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20037, United States

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GSK Investigational Site

Boca Raton, Florida, 33486, United States

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GSK Investigational Site

Jupiter, Florida, 33458, United States

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GSK Investigational Site

Miami, Florida, 33136, United States

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GSK Investigational Site

Miami, Florida, 33169, United States

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GSK Investigational Site

Orlando, Florida, 32803, United States

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GSK Investigational Site

Orlando, Florida, 32835, United States

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GSK Investigational Site

Pembroke Pines, Florida, 33024, United States

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GSK Investigational Site

Trinity, Florida, 34655, United States

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GSK Investigational Site

Winter Park, Florida, 32789, United States

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Atlanta, Georgia, 30309, United States

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GSK Investigational Site

Atlanta, Georgia, 30342, United States

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GSK Investigational Site

Honolulu, Hawaii, 96813, United States

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GSK Investigational Site

Boise, Idaho, 83702, United States

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GSK Investigational Site

Idaho Falls, Idaho, 83404-7542, United States

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GSK Investigational Site

Chicago, Illinois, 60612, United States

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GSK Investigational Site

Chicago, Illinois, 60637, United States

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GSK Investigational Site

Indianapolis, Indiana, 46260, United States

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GSK Investigational Site

Atlanta, Kansas, 21287, United States

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GSK Investigational Site

Topeka, Kansas, 66606, United States

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GSK Investigational Site

Baltimore, Maryland, 21201, United States

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Worcester, Massachusetts, 01655-0002, United States

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GSK Investigational Site

Detroit, Michigan, 48201, United States

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GSK Investigational Site

Kalamazoo, Michigan, 49048, United States

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Gulfport, Mississippi, 39501, United States

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GSK Investigational Site

Columbia, Missouri, 65212, United States

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Kansas City, Missouri, 64106, United States

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St Louis, Missouri, 63110, United States

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Omaha, Nebraska, 68131, United States

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GSK Investigational Site

Neptune City, New Jersey, 07753, United States

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GSK Investigational Site

Buffalo, New York, 14209, United States

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GSK Investigational Site

Mineola, New York, 11501, United States

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GSK Investigational Site

New York, New York, 10032, United States

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GSK Investigational Site

Rochester, New York, 14642, United States

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GSK Investigational Site

Durham, North Carolina, 27713, United States

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Columbus, Ohio, 43205, United States

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GSK Investigational Site

Columbus, Ohio, 43210, United States

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GSK Investigational Site

Dayton, Ohio, 45415-2560, United States

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GSK Investigational Site

Mentor, Ohio, 44060, United States

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GSK Investigational Site

Tulsa, Oklahoma, 74136-8303, United States

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GSK Investigational Site

Eugene, Oregon, 97401, United States

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GSK Investigational Site

Portland, Oregon, 97210, United States

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GSK Investigational Site

Langhorne, Pennsylvania, 19047, United States

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GSK Investigational Site

Philadelphia, Pennsylvania, 19140, United States

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Charleston, South Carolina, 29425-6240, United States

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GSK Investigational Site

Rapid City, South Dakota, 57701, United States

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GSK Investigational Site

Chattanooga, Tennessee, 37403, United States

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GSK Investigational Site

Memphis, Tennessee, 38119, United States

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GSK Investigational Site

Nashville, Tennessee, 37212, United States

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GSK Investigational Site

Dallas, Texas, 75231, United States

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GSK Investigational Site

Dallas, Texas, 75390, United States

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GSK Investigational Site

Houston, Texas, 77030, United States

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GSK Investigational Site

Hurst, Texas, 76054, United States

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GSK Investigational Site

San Antonio, Texas, 78229, United States

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GSK Investigational Site

Schertz, Texas, 782154, United States

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Ogden, Utah, 84403, United States

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GSK Investigational Site

Tacoma, Washington, 98405, United States

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Calgary, Alberta, T2H 2G4, Canada

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Oakville, Ontario, L6H 3P1, Canada

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Smiths Falls, Ontario, K7A 4W8, Canada

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Toronto, Ontario, M4G 3E8, Canada

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Montreal, Quebec, H2W 1T8, Canada

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Pointe-Claire, Quebec, H9R 3J1, Canada

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GSK Investigational Site

Arhus C, 8000, Denmark

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Tampere, 33520, Finland

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GSK Investigational Site

Turku, 20520, Finland

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GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69120, Germany

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GSK Investigational Site

Bad Nauheim, Hesse, 61231, Germany

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Bad Lauterberg im Harz, Lower Saxony, 37431, Germany

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GSK Investigational Site

Berlin, 12200, Germany

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GSK Investigational Site

Latina, Lazio, 04100, Italy

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GSK Investigational Site

Rome, Lazio, 00157, Italy

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GSK Investigational Site

Rome, Lazio, 00161, Italy

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GSK Investigational Site

Rome, Lazio, 00168, Italy

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GSK Investigational Site

Monserrato, Sardinia, 09042, Italy

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GSK Investigational Site

Palermo, Sicily, 90127, Italy

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GSK Investigational Site

Milan, 20132, Italy

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GSK Investigational Site

Roma, 00128, Italy

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GSK Investigational Site

Barcelona, 8035, Spain

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GSK Investigational Site

Girona, Spain

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GSK Investigational Site

Madrid, 28040, Spain

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GSK Investigational Site

Sant Joan, ´03550, Spain

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GSK Investigational Site

Tarrasa, Barcelona, 08221, Spain

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GSK Investigational Site

Gothenburg, SE-413 45, Sweden

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GSK Investigational Site

Halmstad, SE-301 85, Sweden

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GSK Investigational Site

Härnösand, 871 82, Sweden

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GSK Investigational Site

Karlskrona, SE- 371 85, Sweden

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GSK Investigational Site

Karlstad, SE-651 85, Sweden

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GSK Investigational Site

Kristianstad, 291 85, Sweden

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GSK Investigational Site

Motala, SE-591 85, Sweden

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GSK Investigational Site

Stockholm, SE-171 76, Sweden

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GSK Investigational Site

Umeå, SE-901 85, Sweden

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GSK Investigational Site

Vaxjo, SE-351 85, Sweden

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GSK Investigational Site

Bath, Somerset, BA1 3NG, United Kingdom

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GSK Investigational Site

Blackburn, BB2 3HH, United Kingdom

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GSK Investigational Site

Bristol, BS2 8HW, United Kingdom

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GSK Investigational Site

Hull, HU3 2RW, United Kingdom

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GSK Investigational Site

London, SE1 9RT, United Kingdom

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GSK Investigational Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

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Related Publications (2)

• 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

• 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 on DEFEND study

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Antibodies, Monoclonal; otelixizumab; 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 13, 2008
• First Posted: May 16, 2008
• Study Start: July 29, 2008
• Primary Completion: January 31, 2012
• Study Completion: January 31, 2012
• Last Updated: October 3, 2017
• Results First Posted: October 3, 2017

Record last verified: 2017-07

Locations

GB (6); ES (5); US (67); CA (6); DE (4); DK (1); FI (2); IT (8); SE (10)