Diabetes Mellitus, Type 1Phase 1RAO112438NCT00946257
Subcutaneous Administration of Otelixizumab to T1DM Patients
A Phase 1 study testing Otelixizumab in people with Diabetes Mellitus, Type 1, run by GlaxoSmithKline at 6 sites in Belgium.
Trial summary
This study will assess the subcutaneous administration of otelixizumab to T1DM patients. The study will provide safety, tolerability, pharmacodynamic and pharmacokinetic information which will enable the identification of appropriate safe and well-tolerated subcutaneous dosage regimens to be used in subsequent… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Otelixizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 6 sitesBelgium
- Study dates
- 8 Jul 2009to 25 Jun 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 mIU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section TBC if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 to sufficiently minimize the risk of pregnancy. Female subjects must agree to use contraception for at least 2 weeks prior to dosing and for at least 60 days after dosing.
- Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 2 weeks after dosing.
- Body weight > or = 50 kg and BMI within the range 18 - 30 kg/m2 (inclusive).
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- Confirmed diagnosis of insulin-requiring T1DM according to the America Diabetes Association criteria and on a relatively stable insulin regimen, with HbAlc > or = 9%.
- Positive for at least one of the following T1DM-related autoantibodies: anti-GAD (glutamic acid decarboxylase) and/or anti IA 2A.
- Random plasma C-peptide level must be above the level of assay detection at Screen. NOTE: If the screening random plasma C-peptide level is undetectable, subjects must have a Mixed Meal Stimulated C-peptide (MMSCP) equal to or greater than 0.15 nmol/L (0.45 ng/mL) to be eligible for study participation.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Average QTcB < 450 msec.
- No history of splenectomy.
- Subject is seropositive for EBV with < 10,000 copies of EBV DNA per 106 lymphocytes as determined by quantitative polymerase chain reaction.
- CD4+ lymphocyte counts within normal limits within the 30 days before the first dose of study drug.
- Chest X-ray with negative finding at screening
- The subject has no 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).
- Laboratory tests normal at screening or judged not clinically significant by the investigator (except for labs relating to T1DM which may include but not limited to HbA1C and glucose).
Who cannot join
- A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines
- Positive for anti Hepatitis C antibody, Hepatitis B surface antigen, and Hepatitis B core antibody at screening
- A positive test for HIV antibody.
- A positive test for syphilis.
- History of regular alcohol consumption within 6 months of the study defined as:
- an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
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- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Significant and/or active disease in any body system outside of type 1 diabetes mellitus. Examples of significant diseases include but are not limited to: coronary artery disease, congestive heart failure, uncontrolled hypertension, emphysema, seizure disorder.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- The subject has previously received otelixizumab or any other anti-CD3 Mab (e.g., OKT3, ChAglyCD3, or OKT3 ala ala) or anti-CD20 Mab (e.g. rituximab) at any time.
- Use of prescription or non-prescription drugs, except insulin, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Subjects who have had a prior allergic reaction, including anaphylaxis, to otelixizumab or any other human, humanized, chimeric, or rodent antibodies.
- History of frequent headaches and/or migraine.
- History of atopy.
- History of hypotension or orthostatic hypotension.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- Subject received a vaccine within 30 days before the first dose of study drug, or requires a vaccine within 30 days after the last dose of study drug.
- Subjects who have experienced a significant systemic infection within 3 months before the first dose of study.
- Pregnant or lactating females
- The subject has clinically significant abnormal laboratory values during the screening period, other than those due to T1DM. Abnormal values are permitted if, upon re-test, the abnormality was resolved.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Belgium6 sites
GSK Investigational Site
Brussels, 1070
GSK Investigational Site
Brussels, 1090
GSK Investigational Site
Ghent, 9000
GSK Investigational Site
Leuven, 3000
GSK Investigational Site
Liège, 4000
GSK Investigational Site
Merksem, 2170
About this study
Official title: A Randomised, Single-blind, Placebo-controlled, Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Ascending Administration of Otelixizumab in Subjects With Type 1 Diabetes Mellitus
This study will assess the subcutaneous administration of otelixizumab to T1DM patients. The study will provide safety, tolerability, pharmacodynamic and pharmacokinetic information which will enable the identification of appropriate safe and well-tolerated subcutaneous dosage regimens to be used in subsequent clinical studies. This study will consist of a screening phase, followed by an in-house phase whereby otelixizumab will be administered to cohorts that will be staggered at each dose level.
Read the detailed description
Otelixizumab is a humanized, aglycosyl, non-mitogenic, anti CD3 monoclonal antibody (MAb) directed against the ε domain of the human lymphocyte antigen CD3, which is currently undergoing phase III clinical trials in adult new-onset type I diabetes mellitus patients and has been evaluated in rheumatoid arthritis and psoriasis patients in small exploratory studies. In previous studies, otelixizumab has been administered by intravenous infusion. This study is a randomised, single-blind, placebo-controlled, study of otelixizumab administered subcutaneously in Type 1 Diabetes Mellitus (T1DM) subjects.
The assessment of otelixizumab in T1DM subjects will provide safety, tolerability, pharmacodynamic and pharmacokinetic information following subcutaneous administration which will enable the identification of appropriate safe and well-tolerated subcutaneous dosage regimens to be used in subsequent clinical studies. This study will consist of a screening phase, followed by an in-house phase whereby otelixizumab will be administered to cohorts that will be staggered at each dose level. Approximately 6 dose levels, covering up to a 10-fold dose range, will be evaluated. A single subcutaneous dose of otelixizumab will be administered on Day 1 and, serial blood samples will be obtained for clinical laboratory testing, determination of pharmacodynamic markers, serum otelixizumab PK parameters, and immunogenicity. Safety and pharmacodynamic data from the previous dose(s) will be evaluated prior to dose escalation or modification to ensure safety and to achieve target systemic peripheral blood pharmacology. Adverse events, laboratory values, vital signs and ECG's will be monitored closely during this study. All subjects in the study will undergo long-term follow-up out to 48 months to monitor and ensure patient safety.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Otelixizumab
- Keywords
- Type 1 Diabetes Mellitus
- 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.
OtelixizumabDrug
A humanized, aglycosyl, non-mitogenic, anti CD3 monoclonal antibody (MAb) directed against the ε domain of the human lymphocyte antigen CD3.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 0.3 mg dose Receives: Drug: Otelixizumab |
| Cohort 2 | Experimental | 0.6 mg dose Receives: Drug: Otelixizumab |
| Cohort 3 | Experimental | 1.2 mg dose Receives: Drug: Otelixizumab |
| Cohort 4 | Experimental | 1.8 mg dose Receives: Drug: Otelixizumab |
| Cohort 5 | Experimental | 2.4 mg dose Receives: Drug: Otelixizumab |
| Cohort 6 | Experimental | 3.0 mg dose Receives: Drug: Otelixizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability after a single dose of otelixizumab in T1DM patients
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2009 (estimated)
- Study start8 Jul 2009
- Primary completion1 Aug 2011
- Study completion25 Jun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 33 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
- NCT00946257
- Sponsor's protocol ID
- 112438
- Acronym
- RAO112438
- Status last verified
- May 2017
- First submitted
- 23 Jul 2009
- Last updated
- 1 Jun 2017
- Results posted
- No
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Single-blind, Placebo-controlled, Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Ascending Administration of Otelixizumab in Subjects With Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT00946257
- Acronym / sponsor ID
- RAO112438 / 112438
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Type 1 Diabetes Mellitus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 8 Jul 2009 (actual)
- Primary completion
- 1 Aug 2011 (actual)
- Study completion
- 25 Jun 2013 (actual)
- First posted
- 24 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the subcutaneous administration of otelixizumab to T1DM patients. The study will provide safety, tolerability, pharmacodynamic and pharmacokinetic information which will enable the identification of appropriate safe and well-tolerated subcutaneous dosage regimens to be used in subsequent clinical studies. This study will consist of a screening phase, followed by an in-house phase whereby otelixizumab will be administered to cohorts that will be staggered at each dose level.
Detailed description
Otelixizumab is a humanized, aglycosyl, non-mitogenic, anti CD3 monoclonal antibody (MAb) directed against the ε domain of the human lymphocyte antigen CD3, which is currently undergoing phase III clinical trials in adult new-onset type I diabetes mellitus patients and has been evaluated in rheumatoid arthritis and psoriasis patients in small exploratory studies. In previous studies, otelixizumab has been administered by intravenous infusion. This study is a randomised, single-blind, placebo-controlled, study of otelixizumab administered subcutaneously in Type 1 Diabetes Mellitus (T1DM) subjects.
The assessment of otelixizumab in T1DM subjects will provide safety, tolerability, pharmacodynamic and pharmacokinetic information following subcutaneous administration which will enable the identification of appropriate safe and well-tolerated subcutaneous dosage regimens to be used in subsequent clinical studies. This study will consist of a screening phase, followed by an in-house phase whereby otelixizumab will be administered to cohorts that will be staggered at each dose level. Approximately 6 dose levels, covering up to a 10-fold dose range, will be evaluated. A single subcutaneous dose of otelixizumab will be administered on Day 1 and, serial blood samples will be obtained for clinical laboratory testing, determination of pharmacodynamic markers, serum otelixizumab PK parameters, and immunogenicity. Safety and pharmacodynamic data from the previous dose(s) will be evaluated prior to dose escalation or modification to ensure safety and to achieve target systemic peripheral blood pharmacology. Adverse events, laboratory values, vital signs and ECG's will be monitored closely during this study. All subjects in the study will undergo long-term follow-up out to 48 months to monitor and ensure patient safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Otelixizumab0.3 mg dose |
| Cohort 2 | Experimental | Drug: Otelixizumab0.6 mg dose |
| Cohort 3 | Experimental | Drug: Otelixizumab1.2 mg dose |
| Cohort 4 | Experimental | Drug: Otelixizumab1.8 mg dose |
| Cohort 5 | Experimental | Drug: Otelixizumab2.4 mg dose |
| Cohort 6 | Experimental | Drug: Otelixizumab3.0 mg dose |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 mIU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section TBC if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 to sufficiently minimize the risk of pregnancy. Female subjects must agree to use contraception for at least 2 weeks prior to dosing and for at least 60 days after dosing.
- Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 2 weeks after dosing.
Key exclusion criteria (23 listed)
- A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines
- Positive for anti Hepatitis C antibody, Hepatitis B surface antigen, and Hepatitis B core antibody at screening
- A positive test for HIV antibody.
- A positive test for syphilis.
- History of regular alcohol consumption within 6 months of the study defined as:
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 |
|---|---|---|
| OtelixizumabA humanized, aglycosyl, non-mitogenic, anti CD3 monoclonal antibody (MAb) directed against the ε domain of the human lymphocyte antigen CD3. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6 |
Primary outcome
Safety and tolerability after a single dose of otelixizumab in T1DM patients
Time frame: 21 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2017.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Results for study 112438 can be found on the GSK Clinical Study Register.Link 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
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Otelixizumab in people with Diabetes Mellitus, Type 1, run by GlaxoSmithKline at 6 sites in Belgium.
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 17 inclusion and 23 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: finished, as of the sponsor's last update on 1 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Belgium. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety and tolerability after a single dose of otelixizumab in T1DM patients (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jun 2017; AzTrials last refreshed its copy on 8 Nov 2026.