Diabetes Mellitus, Type 1Phase 2TTEDDNCT00451321

TRX4 Monoclonal Antibody in Type 1 Diabetes (T1 DM)

A Phase 2 study testing Otelixizumab in people with Diabetes Mellitus, Type 1, run by GlaxoSmithKline at 17 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 12 to 45 years
Conditions the study is for: Diabetes Mellitus, Type 1
What is being tested?: Otelixizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 88 participants
Where: 17 sitesin 2 countries
Study dates: 31 Jul 2006to 1 Dec 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 to 45 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

17 sites in 2 countries.

Country

City, postcode or hospital

17 sites in 2 countries

United States16 sites

GSK Investigational Site
Aurora, Colorado, 80045
GSK Investigational Site
Baltimore, Maryland, 21201
GSK Investigational Site
Birmingham, Alabama, 35294
GSK Investigational Site
Chicago, Illinois, 60637
GSK Investigational Site
Gulfport, Mississippi, 39501
GSK Investigational Site
Jacksonville, Florida, 32207
GSK Investigational Site
Kalamazoo, Michigan, 49048
GSK Investigational Site
Mentor, Ohio, 44060
GSK Investigational Site
Minneapolis, Minnesota, 55455
GSK Investigational Site
Omaha, Nebraska, 68131
GSK Investigational Site
Pinellas Park, Florida, 33781
GSK Investigational Site
Rapid City, South Dakota, 57701
GSK Investigational Site
San Antonio, Texas, 78229-4801
GSK Investigational Site
Walnut Creek, California, 94598
GSK Investigational Site
Washington D.C., District of Columbia, 20037
GSK Investigational Site
Worcester, Massachusetts, 1655

Other trials in United States

Canada1 site

GSK Investigational Site
Toronto, Ontario, M4G 3E8

Other trials in Canada

About this study

Official title: TRX4 Therapeutic Evaluation of Different Multi-Dose Regimens in Type 1 Diabetes Mellitus (TTEDD)

Conditions: Diabetes Mellitus, Type 1
Being tested: Otelixizumab
Keywords: type 1 diabetes mellitus, diabetes mellitus type 1, type 1 diabetes, diabetes mellitus, diabetes
Medical subject headings: Diabetes Mellitus, Type 1, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OtelixizumabDrug
Infusion

Study groups in NCT00451321
Study group	Role	What they receive
otelixizumab	Experimental	Not described Receives: Drug: Otelixizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Pharmacokinetic (PK) samples were obtained 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, samples were collected at pre-dose, EOI, and 3.5, 4, 5, and 8-10 hour post-SOI. The lower limit of quantification was 0.019 micrograms per milliliter (µg/mL). The 'PK summary Population' was defined as participants in the 'All Subjects' Population for whom a pharmacokinetic sample was obtained and analyzed, and who received the full scheduled dose, as specified in the protocol. Only those participants available at the specified time points were analyzed.
Measured: 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
PK samples were obtained 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, samples were collected at pre-dose, EOI, and 3.5, 4, 5, and 8-10 hour post-SOI. The lower limit of quantification was 0.019 µg/mL. Only those participants available at the specified time points were analyzed.
Measured: 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
PK samples were obtained at Baseline, and on all dose days except the final dose day, at pre-dose, EOI, and 4 hour SOI. On Dose Day 5, samples were collected at pre-dose, EOI, and 3.5, 4, 5, and 8-10 hour post-SOI. The lower limit of quantification was 0.019 µg/mL. Only those participants available at the specified time points were analyzed.
Measured: 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
One sample was collected at the screening visit and at Baseline. On dose Day 1, samples were collected at EOI and 4 hour post-SOI. On all other dosing days, samples were collected at pre-dose, EOI and 4 hour post-SOI. To obtain absolute counts for each lymphocyte subset (CD19+ B cells, CD4+CD25hiFoxP3+ T cells, CD8+CD25+FoxP3+ T cells) the proportion of total lymphocytes constituting that subset was multiplied by the total count for the same participant at the same time point. The data was collected on Baseline, Days 1 to 8, Days 14, 21, 28, Weeks 6, 8, 10, 12, Months 4, 5, 6, 12, 24, 36 and 48. However data for Days 8 and 28 is presented. The 'Pharmacodynamic (PD) summary population' was defined as participants in the 'All Subjects' Population for whom a PD sample was obtained and analyzed and who received the full scheduled dose, as specified in the protocol.
Measured: Day 8 and 28
Mean Lymphocytes Subsets (CD4+ T Cells, CD8+ T Cells) Count
One sample was collected at the screening visit and at Baseline. On dose Day 1, samples were collected at EOI and 4 hour post-SOI. On all other dosing days, samples were collected at pre-dose, EOI and 4 hour post-SOI. To obtain absolute counts for each lymphocyte subset (CD4+ T cells, CD8+ T cells) the proportion of total lymphocytes constituting that subset was multiplied by the total count for the same participant at the same time point. The data was collected on Baseline, Days 1 to 8, Days 14, 21, 28, Weeks 6, 8, 10, 12, Months 4, 5, 6, 12, 24, 36 and 48. However data for Days 8 and 28 is presented.
Measured: Day 8 and 28
Mean CD4+/CD8+ Ratio
One sample was collected at the screening visit and at Baseline. On dose Day 1, samples were collected at EOI and 4 hour post-SOI. On all other dosing days, samples were collected at pre-dose, EOI and 4 hour post-SOI. CD4+/CD8+ ratio was determined by dividing the absolute count of CD4+ T cells by the absolute count of CD8+ T cells for the same participant at the same time point. The data was collected on Baseline, Days 1 to 8, Days 14, 21, 28, Weeks 6, 8, 10, 12, Months 4, 5, 6, 12, 24, 36 and 48. However data for Days 8 and 28 is presented.
Measured: Day 8 and 28
Percent Lymphocytes Subsets (CD25+CD8+Tregs) Count
One sample was collected at the screening visit and at Baseline. On dose Day 1, samples were collected at EOI and 4 hour post-SOI. On all other dosing days, samples were collected at pre-dose, EOI and 4 hour post-SOI. The data was collected on Baseline, Days 1 to 8, Days 14, 21, 28, Weeks 6, 8, 10, 12, Months 4, 5, 6, 12, 24, 36 and 48. However data for Days 8 and 28 is presented.
Measured: Day 8 and 28
Amounts of Cell-bound Otelixizumab on CD4+ and CD8+ T Cells
Samples were planned to analyze at the screening visit and at Baseline. Further 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.
Measured: 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.
Saturation of CD4+ and CD8+ T Cells With Otelixizumab
Samples were planned to analyze at the screening visit and at Baseline. Further 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.
Measured: 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.
CD3/TCR Complexes on CD4+ and CD8+ T Cells
Samples were planned to analyze at the Screen visit and at Baseline. Further 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.
Measured: 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.
Number of Participants With Detectable Anti-otelixizumab Antiglobulin Response
Anti-otelixizumab antibody levels were determined by ELISA. Immunogenicity data was not collected for Cohort 5 (5 day dosing) participants.
Measured: Up to Month 48
Number of Participants With Use of Analgesics, Antihistamines and IV Hydration as Concomitant Medication During Dosing Days
Ibuprofen (analgesic) was given orally as follows: 400-800 mg 2 hour before SOI, 400-800 mg 2 hour after SOI, 400-800 mg 6 hour after SOI, and 400-800 mg at bedtime. If ibuprofen was contraindicated, acetaminophen was used in place of ibuprofen. Acetaminophen doses were adjusted so as it did not exceed 1000 mg per 6 hour or 4000 mg per day. A non-sedating antihistamine (cetirizine) was administered approximately 1 hour prior to each infusion of study drug. The recommended initial dose of cetirizine was 5 mg or 10 mg per day in adults and children aged 12 years and older. Normal saline solution was administered IV as needed to maintain hydration.
Measured: Up to Day 8
Change From Baseline in Percent Glycosylated Hemoglobin (HbA1c)
Participants were seen weekly during the first 4 weeks post-dose and then every other week through Week 12. After Week 12, visits occurred every 1 to 3 months through Month 18, which completes the Core Study up to Month 48 (follow up). Day 1 pre-dose value was considered as Baseline value. Change from Baseline was post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Jul 20061 Dec 2011

First posted23 Mar 2007 (estimated)
Study start31 Jul 2006
Primary completion1 Dec 2011
Study completion1 Dec 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 88 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00451321
Sponsor's protocol ID: 115493
Other IDs: TRX4005
Acronym: TTEDD
Status last verified: Oct 2017
First submitted: 21 Mar 2007
Last updated: 13 Nov 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

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.
PubMed 15972866

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 13 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: TRX4 Therapeutic Evaluation of Different Multi-Dose Regimens in Type 1 Diabetes Mellitus (TTEDD)
ClinicalTrials.gov ID: NCT00451321
Acronym / sponsor ID: TTEDD / 115493
Conditions: Diabetes Mellitus, Type 1
Keywords: type 1 diabetes mellitus, diabetes mellitus type 1, type 1 diabetes, diabetes mellitus, diabetes
Phase: Phase 2
Study type: Interventional
Recruitment status: Terminated
Enrolment: 88 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Collaborators: Juvenile Diabetes Research Foundation
Study start: 31 Jul 2006 (actual)
Primary completion: 1 Dec 2011 (actual)
Study completion: 1 Dec 2011 (actual)
First posted: 23 Mar 2007 (estimated)
Results: Posted 13 Nov 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
otelixizumab	Experimental	Drug: Otelixizumab

Who may qualify

Ages: 12 to 45 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (3 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OtelixizumabInfusion	Drug	otelixizumab

Primary outcome

Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to Month 24
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.
Number of Participants With Cytokine Release AE
Time frame: Up to Month 24
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.
Number of Participants With Abnormal Hematology Values of Potential Clinical Concern (PCC)
Time frame: Up to Month 48
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.
Number of Participants With Abnormal Clinical Chemistry Values of PCC
Time frame: Up to Month 48
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.
Number of Participants With Abnormal Urinalysis Dipstick Results
Time frame: Up to Month 48
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.
Mean Overall Maximum Cytokines Level
Time frame: Up to Week 8
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.
Number of Participants With Positive Epstein Barr Virus (EBV) Viral Load
Time frame: Up to Month 18
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.

13 secondary outcomes

Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUClast) of Otelixizumab
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 8 and 28
Mean Lymphocytes Subsets (CD4+ T Cells, CD8+ T Cells) Count
Time frame: Day 8 and 28
Mean CD4+/CD8+ Ratio
Time frame: Day 8 and 28
Percent Lymphocytes Subsets (CD25+CD8+Tregs) Count
Time frame: Day 8 and 28
Amounts of Cell-bound Otelixizumab on CD4+ and CD8+ T Cells
Time frame: 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.
Saturation of CD4+ and CD8+ T Cells With Otelixizumab
Time frame: 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.
CD3/TCR Complexes on CD4+ and CD8+ T Cells
Time frame: 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.
Number of Participants With Detectable Anti-otelixizumab Antiglobulin Response
Time frame: Up to Month 48
Number of Participants With Use of Analgesics, Antihistamines and IV Hydration as Concomitant Medication During Dosing Days
Time frame: Up to Day 8
Change From Baseline in Percent Glycosylated Hemoglobin (HbA1c)
Time frame: Baseline and up to Month 48

Results and safety

Results posted to the registry on 13 Nov 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Otelixizumab <3.0 mg	8	1
Otelixizumab 3.1 mg	15	10
Otelixizumab 3.1 mg (5 Days)	18	0
Otelixizumab 4.35 mg	19	7
Otelixizumab 4.35 mg (ITC-15)	7	0
Otelixizumab 4.35 mg (ITC-30)	9	0
Otelixizumab 6.85 mg	6	0
Otelixizumab 8.85 mg	6	0

Primary outcome: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: Up to Month 24. Count of participants. Unit: Participants

Measure	Otelixizumab <3.0 mg n = 8	Otelixizumab 3.1 mg n = 15	Otelixizumab 3.1 mg (5 Days) n = 18	Otelixizumab 4.35 mg n = 19	Otelixizumab 4.35 mg (ITC-15) n = 7	Otelixizumab 4.35 mg (ITC-30) n = 9	Otelixizumab 6.85 mg n = 6	Otelixizumab 8.85 mg n = 6
Any AEs	8	15	18	18	7	9	6	6
Any SAEs	1	2	1	0	0	1	1	2

Population analysed: The 'All Subjects population' was defined as all participants who received at least one dose of study medication and was used in all study population and safety analyses. Participants from all 7 cohorts who had received a total dose \<3.0 mg were analyzed as a separate treatment group.

Primary outcome: Number of Participants With Cytokine Release AE

Time frame: Up to Month 24. Count of participants. Unit: Participants

Measure	Otelixizumab <3.0 mg n = 8	Otelixizumab 3.1 mg n = 15	Otelixizumab 3.1 mg (5 Days) n = 18	Otelixizumab 4.35 mg n = 19	Otelixizumab 4.35 mg (ITC-15) n = 7	Otelixizumab 4.35 mg (ITC-30) n = 9	Otelixizumab 6.85 mg n = 6	Otelixizumab 8.85 mg n = 6
Value	8	11	18	17	7	9	6	6

Population analysed: All subjects Population. Participants from all 7 cohorts who had received a total dose \<3.0 mg were analyzed as a separate treatment group.

Primary outcome: Number of Participants With Abnormal Hematology Values of Potential Clinical Concern (PCC)

Time frame: Up to Month 48. Count of participants. Unit: Participants

Measure	Otelixizumab <3.0 mg n = 8	Otelixizumab 3.1 mg n = 15	Otelixizumab 3.1 mg (5 Days) n = 18	Otelixizumab 4.35 mg n = 19	Otelixizumab 4.35 mg (ITC-15) n = 7	Otelixizumab 4.35 mg (ITC-30) n = 9	Otelixizumab 6.85 mg n = 6	Otelixizumab 8.85 mg n = 6
Lymphocytes, low	4	12	18	17	7	9	5	5
WBC, low	3	4	12	5	3	5	3	4
Hemoglobin, high	1	0	0	0	0	0	0	0
Neutrophils, low	1	2	11	1	3	2	3	2
Platelets, low	0	2	4	2	0	0	0	0
Platelets, high	0	0	0	1	0	1	1	0

Population analysed: All subjects Population. Participants from all 7 cohorts who had received a total dose \<3.0 mg were analyzed as a separate treatment group.

Primary outcome: Number of Participants With Abnormal Clinical Chemistry Values of PCC

Time frame: Up to Month 48. Count of participants. Unit: Participants

Measure	Otelixizumab <3.0 mg n = 8	Otelixizumab 3.1 mg n = 15	Otelixizumab 3.1 mg (5 Days) n = 18	Otelixizumab 4.35 mg n = 19	Otelixizumab 4.35 mg (ITC-15) n = 7	Otelixizumab 4.35 mg (ITC-30) n = 9	Otelixizumab 6.85 mg n = 6	Otelixizumab 8.85 mg n = 6
ALT, high	1	1	2	1	0	0	1	0
AST, high	1	0	1	0	0	0	0	0
Fasting glucose, high	1	0	1	0	1	0	0	0
Fasting glucose, low	0	2	0	2	1	2	1	0
Potassium, high	1	0	0	0	0	0	0	0
Bicarbonate, high	0	0	2	0	0	0	0	0
Bicarbonate, low	0	1	1	0	1	1	0	0
Calcium, low	0	1	0	0	1	0	1	1

Population analysed: All subjects Population. Participants from all 7 cohorts who had received a total dose \<3.0 mg were analyzed as a separate treatment group.

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: All SAEs and non-SAEs were collected up to Month 24. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Otelixizumab <3.0 mg	1 of 8 (12.5%)	8 of 8 (100%)	0 of 8
Otelixizumab 3.1 mg	2 of 15 (13.3%)	15 of 15 (100%)	0 of 15
Otelixizumab 3.1 mg (5 Days)	1 of 18 (5.6%)	18 of 18 (100%)	0 of 18
Otelixizumab 4.35 mg	0 of 19 (0%)	18 of 19 (94.7%)	0 of 19
Otelixizumab 4.35 mg (ITC-15)	0 of 7 (0%)	7 of 7 (100%)	0 of 7
Otelixizumab 4.35 mg (ITC-30)	1 of 9 (11.1%)	9 of 9 (100%)	0 of 9
Otelixizumab 6.85 mg	1 of 6 (16.7%)	6 of 6 (100%)	0 of 6
Otelixizumab 8.85 mg	2 of 6 (33.3%)	6 of 6 (100%)	0 of 6

Limitations and caveats (from the sponsor): This study was terminated on 15 December 2011

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 15972866Keymeulen 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.
Click here for more information on the TTEDD studyLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

17 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Otelixizumab in people with Diabetes Mellitus, Type 1, run by GlaxoSmithKline at 17 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Up to Month 24). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00451321, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2017.