Behcet's Disease
Conditions
Brief summary
The primary outcome measure of the study is to demonstrate the safety and tolerability of GSK1070806 in the Behcet's disease population at 24 weeks, with biochemical and clinical efficacy and mechanistic studies to further explore the pathogenesis of Behcet's disease important secondary and exploratory outcomes.
Interventions
DRUGGSK1070806
Single 10mg/kg infusion on Day 0
Sponsors
Cambridge University Hospitals NHS Foundation Trust
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have given written informed consent to participate * Be aged 18 years and over * Have a diagnosis of Behcet's disease (according to the International Study Group (ISG) diagnostic guidelines or International Criteria for BD (ICBD)). * Have active disease, severe enough to necessitate the use of biological therapy at the time of enrolment (i.e. Subjects have refractory disease as defined by the UK Centres of Excellence criteria as failure to respond to steroid and/or immunosuppressive therapy with significant or major organ-threatening disease.
Exclusion criteria
1. Age under 18 years 2. Allergies to humanized monoclonal antibodies 3. Subjects who have received any of the following agents within 364 days of day 0: 1. Alemtuzumab 2. Rituximab or any other B cell depleting or modulating biological agent 4. Subjects who have received any of the following agents within 180 days of day 0: 1. Cyclophosphamide 2. Anti-thymocyte globulin 5. Subjects who have received any of the following agents within 90 days of Day 0: 1. Intravenous immunoglobulin (IVIG) 2. Plasmapheresis 6. Subjects who have received any of the following agents within 30 days of Day 0: 1. Anti-TNF (e.g. adalimumab, etanercept, infliximab) 2. Anti-IL-6 therapy (e.g. tocilizumab) 3. Interleukin-1 receptor antagonist (e.g. anakinra) 4. Alpha interferon 5. Any live vaccine 7. Subjects who have received any other investigational product within 30 days, 5 half lives or twice the duration of the biological effect, whichever is longer. 8. Subjects required more than 15mg prednisolone daily in the 4 week run in phase. 9. Positive human immunodeficiency virus (HIV) antibody test 10. Positive serology for Hepatitis B (HB), defined as: (i) HB surface antigen positive (HBsAg+) OR (ii) HB core antibody positive (HBcAb+) 11. Positive Hepatitis C (HCV) antibody test 12. Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posterior anterior and lateral), and a positive (not indeterminate) QuantiFERON®-TB Gold test. 13. Evidence of chronic infection requiring long term antimicrobial therapy 14. Serum IgG level \< 3g/l 15. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years, and carcinoma in situ of the uterine cervix. 16. QTc interval (single or average) \> 480msec or in subjects with bundle branch block QTc \> 500msec (these criteria do not apply to subjects with predominantly paced rhythm). 17. Liver function: ALT \> 2xULN and bilirubin \> 1.5 ULN (isolated bilirubin \> 1.5 ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%) 18. Compliance: is unlikely to comply with scheduled study visits based on investigator judgment or has a history of substance abuse, psychiatric disorder or condition that may compromise communication with the investigator 19. Women who are pregnant or breast feeding 20. Women of child bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for one month before and 12 months after administration of GSK1070806
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The occurrence of all moderate, severe and life threatening adverse events | 24 weeks | Events that that are possibly, probably or definitely attributable to a single IV dose of GSK1070806 (10mg/kg) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All adverse events, including mild events | 24 weeks | Events that that are possibly, probably or definitely attributable to a single IV dose of GSK1070806 (10mg/kg) |
| Measurement of disease activity | 24 weeks | Using a clinical scoring tool, the Behcet's disease current activity form (BDCAF) |
| Measurement of the accumulation of damage | 24 weeks | Using a clinical scoring tool, the Vasculitis Damage Index (VDI) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Comparison of serum free IL-18 and total IL-18 levels | 6 weeks | Pre and post GSK1070806 |
| Comparison of downstream Th1 cytokines | 6 weeks | Including interferon gamma, IP-10, IL-10, IL-2, IL-1β and TNF. Pre and post GSK1070806. |
Countries
United Kingdom
Contacts
Primary ContactRona M Smith, MD MRCP
Outcome results
None listed