TRX4 Monoclonal Antibody in Type 1 Diabetes (T1 DM)

NCT00451321 | Terminated Phase 2 Results

• 2 other identifiers: 115493TRX4005
• Study Type: interventional
• Target: 88
• Locations: 2 countries
• Sites: 17

Brief Summary

The purpose of this study is to optimize several multi-dose regimens of otelixizumab, determine the highest biologically active dose, evaluate biomarkers and surrogates of efficacy, and to evaluate the effects of each multi-dose regimen of otelixizumab against standard safety and efficacy parameters.

Conditions

Diabetes Mellitus, Type 1

Keywords

type 1 diabetes mellitus; diabetes mellitus type 1; type 1 diabetes; diabetes mellitus; diabetes

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)

  AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

  Up to Month 24

• Number of Participants With Cytokine Release AE

  AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Cytokine release AEs were defined as occurring during dosing or within a limited time window after the last dose.

  Up to Month 24

• Number of Participants With Abnormal Hematology Values of Potential Clinical Concern (PCC)

  Hematology parameters: hemoglobin, white blood cell (WBC) count, basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were assessed for abnormal PCC values. Data for abnormal parameters (high and low) is presented. Only those parameters for which at least one value of PCC was reported are summarized.

  Up to Month 48

• Number of Participants With Abnormal Clinical Chemistry Values of PCC

  Clinical chemistry parameters: alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, gamma-glutamyl transferase, lactate dehydrogenase, lipids, blood urea nitrogen, creatinine, uric acid, sodium, potassium, chloride, carbon dioxide, creatinine phosphokinase, albumin, calcium, magnesium, glucose, phosphate, bicarbonate and total protein were assessed for abnormal PCC values. Data for abnormal parameters (high and low) is presented. Only those parameters for which at least one value of PCC was reported are summarized.

  Up to Month 48

• Number of Participants With Abnormal Urinalysis Dipstick Results

  Urinalysis parameters: Occult blood, Glucose urine, Ketones, Leukocyte esterase, Nitrite, pH, Protein urine were assessed. Abnormal values for occult blood and ketones were presented as 1+, 2+ and 3+ (the plus sign increases with a higher level of parameters: 1+=slightly positive, 2+=positive, 3+=high positive). Abnormal glucose urine values were presented as 50, 100, 250 and 1000 mg/dL. Abnormal nitrite values were presented as 'positive', and abnormal urine protein values were presented as 30 and 100 mg/dL.

  Up to Month 48

• Mean Overall Maximum Cytokines Level

  Levels of cytokines: interferon (IFN)-gamma, interleukin (IL)-10, IL-6 and tumor necrosis factor (TNF)-alpha were assessed. One sample was collected at Baseline, on dose Day 1 at 1, 2, 3, and 8 hours post-end of infusion (EOI) and on all other dosing days at pre-dose, and 1, 2, 3, and 8 hour post-EOI. After the completion of dosing, on Day 21 and Week 8, only the IL-10 level was assessed in the cytokine blood sample.

  Up to Week 8

• Number of Participants With Positive Epstein Barr Virus (EBV) Viral Load

  EBV load was measured using quantitative polymerase chain reaction (PCR) method. If a participant had an EBV viral load of \>100,000 copies/10\^6 peripheral blood mononuclear cells (c/10\^6 PBMC) lymphocytes at any time post-dose, the test was repeated immediately. Data for participants with abnormal viral load is presented.

  Up to Month 18

Secondary Outcomes (13)

• Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUClast) of Otelixizumab

  At Baseline, and on all dose days except the final dose day, at pre-dose, EOI, and 4 hour post-start of infusion (SOI). On Dose Day 5, at pre-dose, EOI, and 3.5, 4, 5, and 8-10 hour post-SOI.

• Maximum Plasma Drug Concentration (Cmax) of Otelixizumab

  At Baseline, and on all dose days except the final dose day, at pre-dose, EOI, and 4 hour post-SOI. On Dose Day 5, at pre-dose, EOI, and 3.5, 4, 5, and 8-10 hour post-SOI.

• Time of Last Quantifiable Drug Concentration (Tlast) and Time of Occurrence of Maximum Plasma Drug Concentration (Tmax) of Otelixizumab

  At Baseline, and on all dose days except the final dose day, at pre-dose, EOI, and 4 hour post-SOI. On Dose Day 5, at pre-dose, EOI, and 3.5, 4, 5, and 8-10 hour post-SOI.

• Mean Lymphocytes Subsets (CD19+ B Cells, CD4+CD25hiFoxP3+ T Cells, CD8+CD25+FoxP3+ T Cells) Count

  Day 8 and 28

• Mean Lymphocytes Subsets (CD4+ T Cells, CD8+ T Cells) Count

  Day 8 and 28

Study Arms (1)

otelixizumab

EXPERIMENTAL

Drug: Otelixizumab

Interventions

Otelixizumab DRUG

Infusion

otelixizumab

Eligibility Criteria

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

You may qualify if:

• Adults 12 to 45 years old who are in good general health
• Confirmed diagnosis of insulin requiring type 1 diabetes mellitus with good glycemic control
• Measurable C-peptide levels

You may not qualify if:

• Females must not be pregnant or lactating and willing to practice contraception
• No prior malignancy, other than non-melanoma skin cancer
• Body Mass Index (BMI) \> 32 at screening

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (17)

GSK Investigational Site

Birmingham, Alabama, 35294, United States

Location

GSK Investigational Site

Walnut Creek, California, 94598, United States

Location

GSK Investigational Site

Aurora, Colorado, 80045, United States

Location

GSK Investigational Site

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

Location

GSK Investigational Site

Jacksonville, Florida, 32207, United States

Location

GSK Investigational Site

Pinellas Park, Florida, 33781, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21201, United States

Location

GSK Investigational Site

Worcester, Massachusetts, 1655, United States

Location

GSK Investigational Site

Kalamazoo, Michigan, 49048, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55455, United States

Location

GSK Investigational Site

Gulfport, Mississippi, 39501, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68131, United States

Location

GSK Investigational Site

Mentor, Ohio, 44060, United States

Location

GSK Investigational Site

Rapid City, South Dakota, 57701, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229-4801, United States

Location

GSK Investigational Site

Toronto, Ontario, M4G 3E8, Canada

Location

Related Publications (1)

• 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

Related Links

• Click here for more information on the TTEDD study

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

otelixizumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

This study was terminated on 15 December 2011

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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2007
• First Posted: March 23, 2007
• Study Start: July 31, 2006
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: November 13, 2017
• Results First Posted: November 13, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

US (16); CA (1)