Diabetes Mellitus, Type 1Phase 2NCT01222078
Investigating Re-Dosing With Otelixizumab in Adults With Newly-Diagnosed Type 1 Diabetes Mellitus
A Phase 2 study testing otelixizumab in people with Diabetes Mellitus, Type 1, run by GlaxoSmithKline at 2 sites in 2 countries.
Trial summary
The purpose of this study to assess the safety and tolerability of re-dosing at 6 months with otelixizumab (given as an 8-day series of intravenous infusions) in adult subjects with newly diagnosed type 1 diabetes mellitus Read more about this study
- Who is it for?
- Ages 18 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
- 1 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 22 Nov 2010to 19 May 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 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female, aged 18 to 45 years. Women are allowed if they are of non-childbearing potential or agree to use one of the contraception methods listed in the protocol.
- Diagnosis of type 1 autoimmune diabetes mellitus according to ADA and WHO criteria
- No more than 90 days between diagnosis and the first dose of study drug.
- Currently requires insulin for T1DM treatment, or has required insulin at some time between diagnosis and the first dose of study drug.
- 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); or 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.
- Stimulated C-peptide level greater than 0.20 nmol/L and less than or equal to 3.50 nmol/L
- Body mass index not greater than 32 kg/m2.
- QTc <450 millisecond (msec) or <480msec for patients with Bundle Branch Block
Who cannot join
- Pregnant, breastfeeding, or planning to become pregnant from the beginning of the screening period or at least 14 days prior to initial dosing until at least 60 days after the last dose of the second treatment course of study drug.
- Current or prior malignancy, other than non-melanoma skin cancer (subject must have had fewer than 5 occurrences of non-melanoma skin cancer, and the last occurrence must not be within 3 months of study entry).
- Clinically significant abnormal laboratory values during the Screening period, other than those due to T1DM. Permitted ranges for selected laboratory values are shown in the protocol. A clinically significant abnormal value will not result in exclusion if, upon re test, the abnormality is resolved or becomes clinically insignificant.
- Significant and/or active disease in any body system likely to increase the risk to the subject or interfere with the subject's participation in or completion of the study. Examples of significant diseases include, but are not limited to, coronary artery disease, congestive heart failure, uncontrolled hypertension, renal failure, emphysema, history of bleeding peptic ulcers, history of seizure(s), addiction to illicit drugs, and alcohol abuse.
- Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), presence of hepatitis B surface antigen (HBsAg), positive hepatitis C test result within 3 months of screening
- Significant systemic infection during the 6 weeks before the first dose of study drug (e.g., infection requiring hospitalisation, major surgery, or IV antibiotics to resolve; other infections, e.g., bronchitis, sinusitis, localised cellulitis, candidiasis, or urinary tract infections, must be assessed on a case-by-case basis by the investigator regarding whether they are serious enough to warrant exclusion).
Show all 19Show fewer
- History of current or past active tuberculosis infection and or latent tuberculosis infection. Further details are given in the protocol.
- A positive test for human immunodeficiency virus (HIV) antibody or risk factors which predispose subject to HIV infection.
- EBV viral load greater than or = to 10,000 copies per 10xe6 peripheral blood mononuclear cells (PBMCs) as determined by quantitative polymerase chain reaction (qPCR). If there is any clinical suspicion that a subject who is EBV seronegative and with EBV PCR <10,000 copies per 10xe6 PBMCs has symptoms consistent with infectious mononucleosis prior to administration of study drug, then a monospot test result must be negative before the subject can be dosed.
- A positive test for syphilis.
- Had a potent immunosuppressive agent (e.g., systemic high-dose corticosteroids on a chronic basis, methotrexate, cyclosporine, or anti-TNF agents) within the 30 days before the first dose of study drug, or expecting to require such treatment within 3 months after the last dose of study drug. (Intranasal, inhaled, and topical corticosteroid medications are permitted if used at recommended dosages.)
- Used an atypical antipsychotic drug (e.g., risperidone [Risperdal], quetiapine [Seroquel], or clozapine [Clozaril]) within the 30 days before first dose of study drug, or expecting to require such treatment during the study.
- Received a vaccine within the 30 days before the first dose of study drug, or expecting to require a vaccine during the dosing period or the 30 days after the last dose of study drug.
- Previously received otelixizumab or any other anti CD3 monoclonal antibody, e.g., OKT3 (muromonab or Orthoclone), ChAglyCD3, or hOKT3γ1 (ala ala), or not willing to refrain from using any such antibody for the planned duration of study participation (18 months after the last dose of study drug).
- Previously received an anti lymphocyte monoclonal antibody, such as anti-CD20, anti-thymocyte globulin (ATG), rituximab (Rituxan), or alemtuzumab (Campath), or planning to use any such antibody during the planned duration of study participation (18 months after the last dose of study drug).
- Had an investigational drug within the 3 months before the first dose of study drug or planning to take an investigational drug within18 months of the last dose of study drug.
- Have donated any plasma or blood within 45 days before the first dose of study drug.
- Prior allergic reaction, including anaphylaxis, to any human, humanised, chimeric, or rodent antibody.
- Undergone a major surgical procedure within 30 days before the first dose of study drug, or planning to undergo any such surgery within 3 months after the last dose of study drug.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Evaluation of the Safety and Tolerability of Re-dosing With Intravenous (iv) Otelixizumab in Adult Subjects With Newly Diagnosed Type 1 Diabetes Mellitus
The purpose of this study to assess the safety and tolerability of re-dosing at 6 months with otelixizumab (given as an 8-day series of intravenous infusions) in adult subjects with newly diagnosed type 1 diabetes mellitus
Read the detailed description
The primary objective of this phase IIa, open-label, multi-centre study is to assess the safety, tolerability and immunogenicity of re-dosing at 6 months with an 8 consecutive day series of otelixizumab intravenous (IV) infusions in 8 adult subjects with newly diagnosed type 1 diabetes mellitus (T1DM). Although it is hoped that the β cell preserving effect of otelixizumab will be long-lasting, it is possible that the effect may decline over time and thus T1DM subjects may require re-treatment. Six months is the minimum time expected between treatments.
After baseline assessments, eligible subjects will receive 8 consecutive days of otelixizumab infusions, each given over a 30 minute period. Prophylaxis for cytokine release syndrome AEs will be given. At Month 6, following a review of any new medical conditions, concomitant medications, lymphocyte count, Epstein Barr Virus (EBV) viral load and other re-dosing eligibility criteria, subjects will be re-treated with the same dosing regimen. Subjects will be followed for 24 months in this study.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- otelixizumab
- Keywords
- newly diagnosed type 1 diabetes mellitus, re-treatment, intravenous otelixizumab, beta-cell preservation
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
otelixizumabBiological
Two treatment courses of otelixizumab given 6 months apart. Each treatment course will consist of 8 consecutive days of otelixizumab intravenous infusions (each given over 30 minutes).
| Study group | Role | What they receive |
|---|---|---|
| otelixizumab | Experimental | otelixizumab Receives: Biological: 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 AEs (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. Study was early terminated and participant withdrew on study Day 164.
Measured: Up to Month 24
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Blood pressure was assessed at sitting position at Baseline and 1 to 7 hours of post-infusion of first treatment period. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Mean Change From Baseline in Respiration Rate
Respiration rate was assessed at sitting position at Baseline and post-treatment. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Mean Change From Baseline in Temperature
Temperature was recorded at sitting position at Baseline and post treatment. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Mean Change From Baseline in Heart Rate
Heart rate was recorded at sitting position at Baseline and post-treatment period. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Number of Participants With Values Outside the Normal Range for Vitals
Vital included assessment of SBP, DBP, respiration rate, heart rate and temperature were assessed at sitting position. Participant did not received re-dose of second treatment period and withdrew on study Day 164 because of early study termination.
Measured: Up to Month 24
Mean Change From Baseline in Value of Albumin and Total Protein
Clinical chemistry parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Mean Change From Baseline in Value of Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Follicle Stimulating Hormone, Gamma Glutamyl Tranferase and Lactate Dehydrogenase
Clinical chemistry parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Mean Change From Baseline in Value of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid
Clinical chemistry parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Mean Change From Baseline in Value of Calcium, Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus and Urea/Blood Urea Nitrogen
Clinical chemistry parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Mean Change From Baseline in Value of Estradiol
Clinical chemistry parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Mean Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count and White Blood Cell Count
Hematology parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Mean Change From Baseline in Glycosylated Hemoglobin Value
Hematology parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Mean Change From Baseline in Hemoglobin Value
Hematology parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Mean Change From Baseline in Red Blood Cell Count
Hematology parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Measured: Baseline and up to Month 24
Mean Epstein-Barr Virus (EBV) Viral Load
Levels of EBV were assessed periodically using Quantitative Polymerase Chain Reaction. If a participant had an EBV viral load of >=10,000 copies per 10^6 Peripheral Blood Mononuclear Cells (PBMCs) at any visit, the test was repeated as soon as possible to confirm this result. If the result was confirmed, the test was repeated weekly for 2 weeks or until the count decreases to < 10,000 copies per 10^6 PBMCs, whichever was longer. The EBV Load remained zero throughout the study. Participant did not received re-dose of second treatment period and withdrew on study Day 164 because of early study termination. The viral load was to measure using unit copies per 10^6 Peripheral Blood Mononuclear Cells (PBMCs)
Measured: Up to Month 24
Mean Change in Total Lymphocyte Count
Total lymphocyte count was planned to be analyzed up to Month 24.
Measured: Baseline and up to Month 24
Mean Change in CD4+ and CD8+ T-cell Counts
CD4+ and CD8+ T cells were planned to be measured before, during and after dose 1, 4 and 8 of first treatment course. Because of the early termination of the study the data was not analyzed.
Measured: Days 1, 4 and 8 of each treatment course
Mean Change in Circulating Peripheral T Lymphocytes
Circulating peripheral T lymphocytes were planned to be measured before, during and after dose 1, 4 and 8 of first treatment course. Because of the early termination of the study the data was not analyzed.
Measured: Days 1, 4 and 8 of each treatment course
Mean Change in Circulating Peripheral CD4+ and CD8+ Subset Counts
Circulating peripheral CD4+ and CD8+ T cells were planned to be measured before, during and after dose 1, 4 and 8 of first treatment course. Because of the early termination of the study the data was not analyzed.
Measured: Days 1, 4 and 8 of each treatment course
Mean Serum Levels of Anti-otelixizumab Binding Antibodies
Antibodies to otelixizumab were planned to be measured at Baseline and at specified post-Baseline visits using a validated immunoassay. If a positive result was detected, the samples were analyzed further in a neutralizing antibody assay to determine if the antibodies were neutralizing. The 12 and 24 month samples were only be taken if a participant had a positive result for antibodies at the last tested time point (Month 9) or if the Month 9 test results were not available.
Measured: Up to Month 24
Proportion of Anti-otelixizumab Neutralizing Antibodies
Antibodies to otelixizumab were planned to be measured at Baseline and at specified post-Baseline visits using a validated immunoassay. If a positive result was detected, the samples were analyzed further in a neutralizing antibody assay to determine if the antibodies were neutralizing. The 12 and 24 month samples were only be taken if a participant had a positive result for antibodies at the last tested time point (Month 9) or if the Month 9 test results were not available.
Measured: Up to Month 24
Secondary outcomes (9)
Mean Circulating Peripheral T Lymphocytes Count
Circulating peripheral T lymphocytes were planned to be measured before, during and after dose 1, 4 and 8 of first treatment course. Because of the early termination of the study the data was not analyzed.
Measured: Day 1, 4 and 8 of each treatment course
Mean Circulating CD4+ and CD8+ Subset Counts
Circulating peripheral CD4+ and CD8+ T cells were planned to be measured before, during and after dose 1, 4 and 8 of first treatment course. Because of the early termination of the study the data was not analyzed.
Measured: Days 1, 4 and 8 of each treatment course
Mean Saturation of CD3 Antigen on Peripheral Blood T Cells
Assessment of CD3 antigen was planned to be done on Day 1, 4 and 8 of first treatment course. The data was planned to be presented with unit Molecules of Equivalent Soluble Fluorochrome (MESF). Because of the early termination of the study the data was not analyzed.
Measured: Days 1, 4 and 8 of each treatment course
Mean Individual Serum Concentrations of Otelixizumab
Because of the early termination of the study the data was not analyzed.
Measured: Pre-dose and EOI on Dosing Day 1, EOI on Dosing Days 2, 3, 5-7 and Pre-dose, EOI, 6 hours post SOI on Dosing days 4 and 8 of each treatment course
Maximum Observed Serum Concentration (Cmax) of Otelixizumab
Because of the early termination of the study the data was not analyzed.
Measured: Pre-dose and EOI on Dosing Day 1, EOI on Dosing Days 2, 3, 5-7 and Pre-dose, EOI, 6 hours post SOI on Dosing days 4 and 8 of each treatment course
Time to Cmax (Tmax) of Otelixizumab
Because of the early termination of the study the data was not analyzed.
Measured: Pre-dose and EOI on Dosing Day 1, EOI on Dosing Days 2, 3, 5-7 and Pre-dose, EOI, 6 hours post SOI on Dosing days 4 and 8 of each treatment course
Area Under the Serum Concentration-time Curve [AUC(0-tlast)] of Otelixizumab
Because of the early termination of the study the data was not analyzed.
Measured: Pre-dose and EOI on Dosing Day 1, EOI on Dosing Days 2, 3, 5-7 and Pre-dose, EOI, 6 hours post SOI on Dosing days 4 and 8 of each treatment course
Time of Last Observed Quantifiable Concentration (Tlast) of Otelixizumab
Because of the early termination of the study the data was not analyzed.
Measured: Pre-dose and EOI on Dosing Day 1, EOI on Dosing Days 2, 3, 5-7 and Pre-dose, EOI, 6 hours post SOI on Dosing days 4 and 8 of each treatment course
Terminal Phase Half-life (Thalf) of Otelixizumab
Because of the early termination of the study the data was not analyzed.
Measured: Pre-dose and EOI on Dosing Day 1, EOI on Dosing Days 2, 3, 5-7 and Pre-dose, EOI, 6 hours post SOI on Dosing days 4 and 8 of each treatment course
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2010 (estimated)
- Study start22 Nov 2010
- Primary completion19 May 2011
- Study completion19 May 2011
Why it stopped: A Phase 3 study recently reported and demonstrated that the dose of otelixizumab in OTX113390 is not effective.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01222078
- Sponsor's protocol ID
- 113390
- Other IDs
- 2010-019157-17
- Status last verified
- Oct 2020
- First submitted
- 7 Oct 2010
- Last updated
- 30 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
GSK has concluded that it is not feasible to publish this study in a peer-reviewed scientific journal because the nature of the study is unlikely to be of interest to a journal. GSK is providing the attached study results summary with a conclusion.
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Safety and Tolerability of Re-dosing With Intravenous (iv) Otelixizumab in Adult Subjects With Newly Diagnosed Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT01222078
- Acronym / sponsor ID
- 113390
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- newly diagnosed type 1 diabetes mellitus, re-treatment, intravenous otelixizumab, beta-cell preservation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: A Phase 3 study recently reported and demonstrated that the dose of otelixizumab in OTX113390 is not effective.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 22 Nov 2010 (actual)
- Primary completion
- 19 May 2011 (actual)
- Study completion
- 19 May 2011 (actual)
- First posted
- 18 Oct 2010 (estimated)
- Results
- Posted 16 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study to assess the safety and tolerability of re-dosing at 6 months with otelixizumab (given as an 8-day series of intravenous infusions) in adult subjects with newly diagnosed type 1 diabetes mellitus
Detailed description
The primary objective of this phase IIa, open-label, multi-centre study is to assess the safety, tolerability and immunogenicity of re-dosing at 6 months with an 8 consecutive day series of otelixizumab intravenous (IV) infusions in 8 adult subjects with newly diagnosed type 1 diabetes mellitus (T1DM). Although it is hoped that the β cell preserving effect of otelixizumab will be long-lasting, it is possible that the effect may decline over time and thus T1DM subjects may require re-treatment. Six months is the minimum time expected between treatments.
After baseline assessments, eligible subjects will receive 8 consecutive days of otelixizumab infusions, each given over a 30 minute period. Prophylaxis for cytokine release syndrome AEs will be given. At Month 6, following a review of any new medical conditions, concomitant medications, lymphocyte count, Epstein Barr Virus (EBV) viral load and other re-dosing eligibility criteria, subjects will be re-treated with the same dosing regimen. Subjects will be followed for 24 months in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| otelixizumab | Experimental | Biological: otelixizumabotelixizumab |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Male or female, aged 18 to 45 years. Women are allowed if they are of non-childbearing potential or agree to use one of the contraception methods listed in the protocol.
- Diagnosis of type 1 autoimmune diabetes mellitus according to ADA and WHO criteria
- No more than 90 days between diagnosis and the first dose of study drug.
- Currently requires insulin for T1DM treatment, or has required insulin at some time between diagnosis and the first dose of study drug.
- 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); or 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.
Key exclusion criteria (19 listed)
- Pregnant, breastfeeding, or planning to become pregnant from the beginning of the screening period or at least 14 days prior to initial dosing until at least 60 days after the last dose of the second treatment course of study drug.
- Current or prior malignancy, other than non-melanoma skin cancer (subject must have had fewer than 5 occurrences of non-melanoma skin cancer, and the last occurrence must not be within 3 months of study entry).
- Clinically significant abnormal laboratory values during the Screening period, other than those due to T1DM. Permitted ranges for selected laboratory values are shown in the protocol. A clinically significant abnormal value will not result in exclusion if, upon re test, the abnormality is resolved or becomes clinically insignificant.
- Significant and/or active disease in any body system likely to increase the risk to the subject or interfere with the subject's participation in or completion of the study. Examples of significant diseases include, but are not limited to, coronary artery disease, congestive heart failure, uncontrolled hypertension, renal failure, emphysema, history of bleeding peptic ulcers, history of seizure(s), addiction to illicit drugs, and alcohol abuse.
- Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), presence of hepatitis B surface antigen (HBsAg), positive hepatitis C test result within 3 months of 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 |
|---|---|---|
| otelixizumabTwo treatment courses of otelixizumab given 6 months apart. Each treatment course will consist of 8 consecutive days of otelixizumab intravenous infusions (each given over 30 minutes). | Biological | otelixizumab |
Primary outcome
Number of Participants With Any Adverse Events (AEs) and Serious AEs (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. Study was early terminated and participant withdrew on study Day 164.
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Baseline and up to Month 24
Blood pressure was assessed at sitting position at Baseline and 1 to 7 hours of post-infusion of first treatment period. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Mean Change From Baseline in Respiration Rate
Time frame: Baseline and up to Month 24
Respiration rate was assessed at sitting position at Baseline and post-treatment. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Mean Change From Baseline in Temperature
Time frame: Baseline and up to Month 24
Temperature was recorded at sitting position at Baseline and post treatment. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Mean Change From Baseline in Heart Rate
Time frame: Baseline and up to Month 24
Heart rate was recorded at sitting position at Baseline and post-treatment period. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Number of Participants With Values Outside the Normal Range for Vitals
Time frame: Up to Month 24
Vital included assessment of SBP, DBP, respiration rate, heart rate and temperature were assessed at sitting position. Participant did not received re-dose of second treatment period and withdrew on study Day 164 because of early study termination.
Mean Change From Baseline in Value of Albumin and Total Protein
Time frame: Baseline and up to Month 24
Clinical chemistry parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Mean Change From Baseline in Value of Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Follicle Stimulating Hormone, Gamma Glutamyl Tranferase and Lactate Dehydrogenase
Time frame: Baseline and up to Month 24
Clinical chemistry parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Mean Change From Baseline in Value of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid
Time frame: Baseline and up to Month 24
Clinical chemistry parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Mean Change From Baseline in Value of Calcium, Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus and Urea/Blood Urea Nitrogen
Time frame: Baseline and up to Month 24
Clinical chemistry parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Mean Change From Baseline in Value of Estradiol
Time frame: Baseline and up to Month 24
Clinical chemistry parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Mean Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count and White Blood Cell Count
Time frame: Baseline and up to Month 24
Hematology parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Mean Change From Baseline in Glycosylated Hemoglobin Value
Time frame: Baseline and up to Month 24
Hematology parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Mean Change From Baseline in Hemoglobin Value
Time frame: Baseline and up to Month 24
Hematology parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Mean Change From Baseline in Red Blood Cell Count
Time frame: Baseline and up to Month 24
Hematology parameters were planned to be analyzed from Baseline to Month 24. Day 1 value was considered to be Baseline value. Change from Baseline was planned to be calculated as any post-Baseline value minus Baseline value.
Mean Epstein-Barr Virus (EBV) Viral Load
Time frame: Up to Month 24
Levels of EBV were assessed periodically using Quantitative Polymerase Chain Reaction. If a participant had an EBV viral load of >=10,000 copies per 10^6 Peripheral Blood Mononuclear Cells (PBMCs) at any visit, the test was repeated as soon as possible to confirm this result. If the result was confirmed, the test was repeated weekly for 2 weeks or until the count decreases to < 10,000 copies per 10^6 PBMCs, whichever was longer. The EBV Load remained zero throughout the study. Participant did not received re-dose of second treatment period and withdrew on study Day 164 because of early study termination. The viral load was to measure using unit copies per 10^6 Peripheral Blood Mononuclear Cells (PBMCs)
Mean Change in Total Lymphocyte Count
Time frame: Baseline and up to Month 24
Total lymphocyte count was planned to be analyzed up to Month 24.
Mean Change in CD4+ and CD8+ T-cell Counts
Time frame: Days 1, 4 and 8 of each treatment course
CD4+ and CD8+ T cells were planned to be measured before, during and after dose 1, 4 and 8 of first treatment course. Because of the early termination of the study the data was not analyzed.
Mean Change in Circulating Peripheral T Lymphocytes
Time frame: Days 1, 4 and 8 of each treatment course
Circulating peripheral T lymphocytes were planned to be measured before, during and after dose 1, 4 and 8 of first treatment course. Because of the early termination of the study the data was not analyzed.
Mean Change in Circulating Peripheral CD4+ and CD8+ Subset Counts
Time frame: Days 1, 4 and 8 of each treatment course
Circulating peripheral CD4+ and CD8+ T cells were planned to be measured before, during and after dose 1, 4 and 8 of first treatment course. Because of the early termination of the study the data was not analyzed.
Mean Serum Levels of Anti-otelixizumab Binding Antibodies
Time frame: Up to Month 24
Antibodies to otelixizumab were planned to be measured at Baseline and at specified post-Baseline visits using a validated immunoassay. If a positive result was detected, the samples were analyzed further in a neutralizing antibody assay to determine if the antibodies were neutralizing. The 12 and 24 month samples were only be taken if a participant had a positive result for antibodies at the last tested time point (Month 9) or if the Month 9 test results were not available.
Proportion of Anti-otelixizumab Neutralizing Antibodies
Time frame: Up to Month 24
Antibodies to otelixizumab were planned to be measured at Baseline and at specified post-Baseline visits using a validated immunoassay. If a positive result was detected, the samples were analyzed further in a neutralizing antibody assay to determine if the antibodies were neutralizing. The 12 and 24 month samples were only be taken if a participant had a positive result for antibodies at the last tested time point (Month 9) or if the Month 9 test results were not available.
9 secondary outcomes
Mean Circulating Peripheral T Lymphocytes Count
Time frame: Day 1, 4 and 8 of each treatment course
Mean Circulating CD4+ and CD8+ Subset Counts
Time frame: Days 1, 4 and 8 of each treatment course
Mean Saturation of CD3 Antigen on Peripheral Blood T Cells
Time frame: Days 1, 4 and 8 of each treatment course
Mean Individual Serum Concentrations of Otelixizumab
Time frame: Pre-dose and EOI on Dosing Day 1, EOI on Dosing Days 2, 3, 5-7 and Pre-dose, EOI, 6 hours post SOI on Dosing days 4 and 8 of each treatment course
Maximum Observed Serum Concentration (Cmax) of Otelixizumab
Time frame: Pre-dose and EOI on Dosing Day 1, EOI on Dosing Days 2, 3, 5-7 and Pre-dose, EOI, 6 hours post SOI on Dosing days 4 and 8 of each treatment course
Time to Cmax (Tmax) of Otelixizumab
Time frame: Pre-dose and EOI on Dosing Day 1, EOI on Dosing Days 2, 3, 5-7 and Pre-dose, EOI, 6 hours post SOI on Dosing days 4 and 8 of each treatment course
Area Under the Serum Concentration-time Curve [AUC(0-tlast)] of Otelixizumab
Time frame: Pre-dose and EOI on Dosing Day 1, EOI on Dosing Days 2, 3, 5-7 and Pre-dose, EOI, 6 hours post SOI on Dosing days 4 and 8 of each treatment course
Time of Last Observed Quantifiable Concentration (Tlast) of Otelixizumab
Time frame: Pre-dose and EOI on Dosing Day 1, EOI on Dosing Days 2, 3, 5-7 and Pre-dose, EOI, 6 hours post SOI on Dosing days 4 and 8 of each treatment course
Terminal Phase Half-life (Thalf) of Otelixizumab
Time frame: Pre-dose and EOI on Dosing Day 1, EOI on Dosing Days 2, 3, 5-7 and Pre-dose, EOI, 6 hours post SOI on Dosing days 4 and 8 of each treatment course
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundGSK has concluded that it is not feasible to publish this study in a peer-reviewed scientific journal because the nature of the study is unlikely to be of interest to a journal. GSK is providing the attached study results summary with a conclusion.
- Individual participant dataSharing planned: No
Related trials for Diabetes Mellitus, Type 1
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
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
2 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 2 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 8 inclusion and 19 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 30 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France, Germany. 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 16 Jun 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 AEs (SAEs) (time frame: Up to Month 24). The study lists 22 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 NCT01222078, 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 30 Oct 2020.