A Safety and Tolerability Study of Otelixizumab in Thyroid Eye Disease
NCT ID: NCT01114503
Last Updated: 2020-10-30
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
TERMINATED
PHASE2
2 participants
INTERVENTIONAL
2010-07-07
2012-08-29
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
In Part A, between one and four groups of 5 patients will receive doses of otelixizumab administered over 8 days. The first dose level will provide a low cumulative dose, this low dose level has been safely administered in previous studies. Safety and clinical response data will be reviewed after 8 weeks, if no clinical response is seen and there are no safety concerns, the dose of otelixizumab will be increased and a new group of subjects will enter Part A. In subsequent groups cumulative medium low, medium high, and high doses of otelixizumab may be investigated. However if a clinical response is seen at the lowest dose the study will move directly to Part B.
In Part B, patients will receive either otelixizumab at the dose set from Part A, over 8 days (5 patients) or methylprednisolone weekly for 12 weeks (5 patients). All dosing will be by intravenous infusion. All participants will undergo long term safety evaluation for 48 months.
Key assessments include vital signs, 12-lead ECG, liver function tests, thyroid function, viral monitoring, monitoring of cortisol and ACTH levels, laboratory safety tests and adverse event (side effect) data. Assessment of GO severity will be evaluated using recommended assessments including clinical activity assessments and quality of life questionnaires. Measurements of exploratory biomarkers (proteins found naturally in the blood) are also included in this study.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Part A
Up to 4 cohorts of 5 patients receive dose rising treatments of otelixizumab
Otelixizumab - low dose
8 day dose rising intravenous infusions of a low dose of otelixizumab
Otelixizumab - medium low dose
8 day dose rising intravenous infusions of a medium low dose of otelixizumab
Otelixizumab - medium high dose
8 day dose rising intravenous infusions of a medium high dose of otelixizumab
Otelixizumab - high dose
8 day dose rising intravenous infusions of a high dose of otelixizumab
Part B - Otelixizumab
Parallel dosing group in Part B receive otelixizumab over 8 days at a dose decided upon results from Part A
Otelixizumab
8 day dose rising intravenous infusions of otelixizumab administered at a dose decided upon results from Part A.
Part B - Methylprednisolone
Parallel dosing group in Part B of weekly doses of methylprednisolone for 12 weeks
Methylprednisolone
Weekly intravenous infusions of methylprednisolone administered as 500 mg per week for 6 weeks and then 250 mg per week for 6 weeks
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Otelixizumab - low dose
8 day dose rising intravenous infusions of a low dose of otelixizumab
Otelixizumab - medium low dose
8 day dose rising intravenous infusions of a medium low dose of otelixizumab
Otelixizumab - medium high dose
8 day dose rising intravenous infusions of a medium high dose of otelixizumab
Otelixizumab - high dose
8 day dose rising intravenous infusions of a high dose of otelixizumab
Otelixizumab
8 day dose rising intravenous infusions of otelixizumab administered at a dose decided upon results from Part A.
Methylprednisolone
Weekly intravenous infusions of methylprednisolone administered as 500 mg per week for 6 weeks and then 250 mg per week for 6 weeks
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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 \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 mIU/ml and estradiol \<40 pg/ml (\<140 pmol/L) is confirmatory\].
* Child-bearing potential and agrees to use one of the agreed contraception methods listed in the protocol for an appropriate period of time to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception for at least 2 weeks prior to dosing and for at least 6 months after the last dose.
* Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until at least 60 days after the last dose.
* Blood test of liver function within normal range
* Body mass index within 18.5 - 35 kg/m2 inclusive
* Capable of giving informed consent and agreement to comply with the study restrictions
* 12-lead ECG within normal limits
* fT4 blood levels within reference range for at least 2 months
* Active Graves' Ophthalmopathy (GO) with a Clinical Activity Score (CAS) of \>/= 3 out of 7
* Moderately severe GO (as defined by EUGOGO guidelines)
* No previous immunosuppressive treatment for GO
* Subject is seropositive for EBV with \<10,000 copies of EBV DNA per 10\^6 lymphocytes (qPCR) or seronegative with no evidence of acute EBV infection (asymptomatic, negative EBV IgM and EBV viral load of \<10,000 per 10\^6 lymphocytes)
* 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)
Exclusion Criteria
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
* 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 test for HIV antibody
* Positive test for syphilis
* History of regular alcohol consumption within 6 months of the study defined as:
* an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or
* an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females)
* Participation 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) or planning to take any investigational drug for the planned duration of study participation (6 months after the last dose of study drug)
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day
* 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
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
* Pregnant females as determined by positive (serum or urine) hCG test at screening or prior to dosing, or lactating females
* Currently receiving or has received corticosteroids or other immunosuppressive agents within the last 3 months
* Evidence of optic neuropathy and/or corneal breakdown
* Immunization with 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
* A CD4+ lymphocyte count outside the range of 0.53 - 1.76 × 109/L during screening
* Significant systemic infection during the 6 weeks before the first dose of study drug
* Received a course of oral antibiotics within 2 weeks of dosing day one
* History of recurrent or chronic infection
* Subject has had a splenectomy
* Subjects with a screening chest X-ray suggestive of TB without documentation of adequate TB treatment
* Any major surgical procedure within the 8 weeks before signing the consent form, or planning to undergo any such surgery within the 3 months after the last dose of study drug
* Clinically significant cardiovascular and/or cerebrovascular disease
* Predisposition to thromboembolic disease, or thromboembolic event (excluding superficial) in past 12 months
* Uncontrolled medical conditions: Significant concurrent, uncontrolled medical condition including, but not limited to renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric disease, or evidence of demyelinating disease
* A condition or situation that, in the investigator's judgment, is likely to cause the subject to be unable or unwilling to participate in study procedures or to complete all scheduled assessments
* Clinically significant abnormal laboratory values during the Screening period, other than those due to GO. Abnormal values are permitted if, upon re-test, the abnormality was resolved
* Unwillingness or inability to follow the procedures outlined in the protocol
* Mentally or legally incapacitated
18 Years
75 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
GlaxoSmithKline
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
GSK Clinical Trials
Role: STUDY_DIRECTOR
GlaxoSmithKline
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
GSK Investigational Site
Newcastle upon Tyne, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2009-016747-19
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
112480
Identifier Type: -
Identifier Source: org_study_id