Primary: efficacy of GSK1605786 at week 12 following twice daily administration at 500 mg in patients with active ulcerative colitis. Secondary: safety and tolerability, time course of the efficacy of GSK1605786 continued for up to 16 weeks, anti-…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Ordinal response (remission, response, or no response) to treatment as assessed
by the MAYO score at week 12.
Secondary outcome
Adverse events, remission, response, endoscopic remission, time to
withdrawal/rescue medication, quality of life (IBDQ questionnaire), biomarkers,
PK, receptor occupancy, TECK/CCL25 and CCR9 expression.
Background summary
GSK1605786A is an orally-administered chemokine antagonist which specifically
blocks the migration of gut-specific T cells, which selectively home to the
intestine.
Ulcerative colitis is a chronic, idiopathic, relapsing inflammatory disorder of
the gastrointestinal tract associated with a dysregulated activation of immune
cell function. It affects the colon and the rectum with patients experiencing
considerable lifestyle disruption and disability including diarrhoea, rectal
blood loss, abdominal pain, malnutrition and anaemia. Currently there is no
curative medical therapy and many patients ultimately require colectomy.
The purpose of this proof of concept study is to investigate the efficacy and
safety of GSK1605786A (500 mg twice daily) administered orally for 16 weeks as
compared with placebo in subjects with moderately-to-severely active ulcerative
colitis.
Study objective
Primary: efficacy of GSK1605786 at week 12 following twice daily administration
at 500 mg in patients with active ulcerative colitis. Secondary: safety and
tolerability, time course of the efficacy of GSK1605786 continued for up to 16
weeks, anti-inflammatory activity (biomarkers), quality of life, PK, CCR9
occupancy, TECK/CCL25 and CCR9 expression in colonic mucosa.
Study design
Multicenter randomized double blind phase II parallel group study.
Randomisation (2:1) to treatment with:
1. GSK1605786A 500 mg twice daily.
2. Placebo.
Treatment duration 16 weeks.
Stratification according to leftsided/extensive disease.
Approx 36 completed patients (45 to be randomized).
Interim analysis after 18 completed patients.
Independent data safety monitoring board.
Intervention
Treatment with GSK1605786A or placebo.
Study burden and risks
Risk: Adverse effects of study medication.
Burden: 11 visits in 20 weeks. Duration 1-6 h.
Sigmoidoscopy (with biopsy) 1-2 x. Blood tests 11x (total approx. 400 ml),
pregnancy test (if relevant) 7x, stool investigation 6x, ECG 3x. 1-4
questionnaires (symptom severity and QoL) 5x.
Diary during 16 weeks, daily registration of abdominal symptoms.
Optional SPECT CT scan 2x
Huis ter Heideweg 62
3705 LZ Zeist
NL
Huis ter Heideweg 62
3705 LZ Zeist
NL
Listed location countries
Age
Inclusion criteria
* Male and female patients 18 years or above with a history of UC for at least 3 months who remain symptomatic despite receiving oral aminosalicylate (with or without topical aminosalicylate) at a dose of >2.4mg/day mesalazine/mesalamine or equivalent for at least 2 weeks.
* At screening: active ulcerative colitis with spread at least 15 cm from the anal verge and MAYO score of 5-10 inclusive.
* Safe contraception for women of childbearing potential.
Exclusion criteria
* Breastfeeding, pregnancy.
* Known coeliac disease, those who follow a gluten-free diet to manage symptoms of suspected coeliac disease and subjects with a positive screening test for celiac disease.
* Known or suspicion of CD, indeterminate colitis, microscopic colitis, ischaemic colitis or radiation-induced colitis.
* Imminent need for surgery for UC.
* Bowel surgery in the past that might interfere with MAYO score.
* Use of prohibited medications (see protocol for details).
* Usual exclusion criteria for biologicals.
* QTc *450 msec (480 msec for those with Bundle Branch Block)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov; registratienummer n.n.b. |
| EudraCT | EUCTR201100281837-NL |
| CCMO | NL38666.018.11 |