A Safety and Tolerability Study of Otelixizumab in Thyroid Eye Disease
The purpose of this study is to investigate the safety and tolerability of otelixizumab in patients with Graves' ophthalmopathy (thyroid eye disease). There is currently no alternative therapy available for this condition other than treatment with steroids, or radiotherapy and surgery. The study also includes a comparison of the current steroid treatment, methylprednisolone, with the proposed new otelixizumab treatment.
Drug: Otelixizumab - low dose
Drug: Otelixizumab - medium low dose
Drug: Otelixizumab - medium high dose
Drug: Otelixizumab - high dose
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomised, Comparator Controlled, Two Part, Open-label Study to Evaluate the Safety, Tolerability and Pharmacodynamics of Multiple Doses of Otelixizumab in Patients With Thyroid Orbitopathy|
- Safety and tolerability as assessed by adverse events, vital signs, clinical laboratory tests and viral load monitoring [ Time Frame: Primary study measures - 6 months. Long term follow up - 48 months ] [ Designated as safety issue: Yes ]
- Assessment of CD3/TCR complex [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- T lymphocyte sub sets counts [ Time Frame: Primary study measures - 6 months. Long term follow up - 48 months ] [ Designated as safety issue: No ]
- European Group on Graves' Orbitopathy (EUGOGO) Clinical Activity Score [ Time Frame: Primary study measures - 6 months. Long term follow up - 48 months ] [ Designated as safety issue: No ]
- Health related quality of life questionnaires (SF-36 & GO-QoL) [ Time Frame: Primary study measures - 6 months. Long term follow up - 48 months ] [ Designated as safety issue: No ]
- Orbital volume as measured by CT scan [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Assessment of anti-otelixizumab antibodies, circulating cytokines and other exploratory tissue biomarkers [ Time Frame: Primary study measures - 6 months. Long term follow up - 48 months ] [ Designated as safety issue: No ]
|Study Start Date:||July 2010|
|Study Completion Date:||August 2012|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
Experimental: Part A
Up to 4 cohorts of 5 patients receive dose rising treatments of otelixizumab
Drug: Otelixizumab - low dose
8 day dose rising intravenous infusions of a low dose of otelixizumabDrug: Otelixizumab - medium low dose
8 day dose rising intravenous infusions of a medium low dose of otelixizumabDrug: Otelixizumab - medium high dose
8 day dose rising intravenous infusions of a medium high dose of otelixizumabDrug: Otelixizumab - high dose
8 day dose rising intravenous infusions of a high dose of otelixizumab
Experimental: Part B - Otelixizumab
Parallel dosing group in Part B receive otelixizumab over 8 days at a dose decided upon results from Part A
8 day dose rising intravenous infusions of otelixizumab administered at a dose decided upon results from Part A.
Active Comparator: Part B - Methylprednisolone
Parallel dosing group in Part B of weekly doses of methylprednisolone for 12 weeks
Weekly intravenous infusions of methylprednisolone administered as 500 mg per week for 6 weeks and then 250 mg per week for 6 weeks
This is a study of otelixizumab, a monoclonal antibody (MAb) directed against the human lymphocyte antigen CD3 (a protein found on a certain type of white blood cell). This will be an open-label, comparator-controlled, two part study to evaluate the safety and tolerability of otelixizumab in patients with Graves' ophthalmopathy (GO). It will also look to see if otelixizumab affects GO and how it works compared to methylprednisolone (the standard treatment for active GO).
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01114503
|GSK Investigational Site|
|Newcastle upon Tyne, United Kingdom, NE1 3BZ|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|