Clinical trial NCT00451321: TRX4 Monoclonal Antibody in Type 1 Diabetes (T1 DM)
Official title: TRX4 Therapeutic Evaluation of Different Multi-Dose Regimens in Type 1 Diabetes Mellitus (TTEDD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: type 1 diabetes mellitus
diabetes mellitus type 1
type 1 diabetes
diabetes mellitus
diabetes
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2007-03-23
Enrollment: 88
Sex: ALL
Minimum age (years): 12
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Month 24
measure: Number of Participants With Cytokine Release AE
timeFrame: Up to Month 24
measure: Number of Participants With Abnormal Hematology Values of Potential Clinical Concern (PCC)
timeFrame: Up to Month 48
measure: Number of Participants With Abnormal Clinical Chemistry Values of PCC
timeFrame: Up to Month 48
measure: Number of Participants With Abnormal Urinalysis Dipstick Results
timeFrame: Up to Month 48
measure: Mean Overall Maximum Cytokines Level
timeFrame: Up to Week 8
measure: Number of Participants With Positive Epstein Barr Virus (EBV) Viral Load
timeFrame: Up to Month 18
Secondary outcomes:
measure: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUClast) of Otelixizumab
timeFrame: 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.
measure: Maximum Plasma Drug Concentration (Cmax) of Otelixizumab
timeFrame: 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.
measure: Time of Last Quantifiable Drug Concentration (Tlast) and Time of Occurrence of Maximum Plasma Drug Concentration (Tmax) of Otelixizumab
timeFrame: 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.
measure: Mean Lymphocytes Subsets (CD19+ B Cells, CD4+CD25hiFoxP3+ T Cells, CD8+CD25+FoxP3+ T Cells) Count
timeFrame: Day 8 and 28
measure: Mean Lymphocytes Subsets (CD4+ T Cells, CD8+ T Cells) Count
timeFrame: Day 8 and 28
measure: Mean CD4+/CD8+ Ratio
timeFrame: Day 8 and 28
measure: Percent Lymphocytes Subsets (CD25+CD8+Tregs) Count
timeFrame: Day 8 and 28
measure: Amounts of Cell-bound Otelixizumab on CD4+ and CD8+ T Cells
timeFrame: At the screening visit and at Baseline. On dose Day 1, at EOI and 4 hour post-SOI. On all other dosing days, at pre-dose, EOI and 4 hour post-SOI up to 48 months.
measure: Saturation of CD4+ and CD8+ T Cells With Otelixizumab
timeFrame: At the screening visit and at Baseline. On dose Day 1, at EOI and 4 hour post-SOI. On all other dosing days, at pre-dose, EOI and 4 hour post-SOI up to 48 months.
measure: CD3/TCR Complexes on CD4+ and CD8+ T Cells
timeFrame: At the Screen visit and at Baseline. On dose Day 1, at EOI and 4 hour post-SOI. On all other dosing days, at pre-dose, EOI and 4 hour post-SOI up to 48 months.
measure: Number of Participants With Detectable Anti-otelixizumab Antiglobulin Response
timeFrame: Up to Month 48
measure: Number of Participants With Use of Analgesics, Antihistamines and IV Hydration as Concomitant Medication During Dosing Days
timeFrame: Up to Day 8
measure: Change From Baseline in Percent Glycosylated Hemoglobin (HbA1c)
timeFrame: Baseline and up to Month 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Walnut Creek
country: United States
facility: GSK Investigational Site
state: California
city: Aurora
country: United States
facility: GSK Investigational Site
state: Colorado
city: Washington, D.C.
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Pinellas Park
country: United States
facility: GSK Investigational Site
state: Florida
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Worcester
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Kalamazoo
country: United States
facility: GSK Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Gulfport
country: United States
facility: GSK Investigational Site
state: Mississippi
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Mentor
country: United States
facility: GSK Investigational Site
state: Ohio
city: Rapid City
country: United States
facility: GSK Investigational Site
state: South Dakota
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.