Clinical trial NCT03522662: Anti IL-18 (GSK1070806) in Behcet's Disease
Official title: An Experimental Medicine Study to Characterise the Importance of IL-18 Production and to Evaluate the Therapeutic Potential of IL-18 Blockade With GSK1070806 in Subjects With Behcet's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Behcet's Disease
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
First posted: 2018-05-11
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: The occurrence of all moderate, severe and life threatening adverse events
timeFrame: 24 weeks
Secondary outcomes:
measure: All adverse events, including mild events
timeFrame: 24 weeks
measure: Measurement of disease activity
timeFrame: 24 weeks
measure: Measurement of the accumulation of damage
timeFrame: 24 weeks
Other outcomes:
measure: Comparison of serum free IL-18 and total IL-18 levels
timeFrame: 6 weeks
measure: Comparison of downstream Th1 cytokines
timeFrame: 6 weeks
Locations:
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital, University of Cambridge NHS Foundation Trust
Study officials:
affiliation: Cambridge University Hospitals NHS Foundation Trust
name: Rona M Smith, MD MRCP
role: PRINCIPAL_INVESTIGATOR
References: