Primary: to assess the efficacy of GSK1605786A compared with placebo as an induction therapy in subjects with moderately-to-severely active Crohn*s disease over 12 weeks. Secondary: Safety, quality of life, healthcare resource utilisation, PK,…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
CDAI decrease from baseline of *100 points at Week 12.
Secondary outcome
CDAI <150 points at week 12, IBDQ score, safety, PK parameters, quality of
life, healthcare related resource utilisation.
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.
Crohn*s disease is a chronic, idiopathic, relapsing inflammatory disorder of
the gastrointestinal tract associated with a dysregulated activation of immune
cell function. It can affect any portion of the gastrointestinal tract but most
commonly affects the terminal small intestine and colon with patients
experiencing considerable lifestyle disruption and disability including
diarrhoea, abdominal pain, malnutrition and anaemia. Currently there is no
curative medical therapy and patients may require treatment for life.
The purpose of this Phase III study is to investigate the efficacy and safety
of two doses of GSK1605786A (500 mg once or twice daily) administered orally
for 12 weeks as compared with placebo in subjects with moderately-to-severely
active Crohn*s disease.
The results of this study are planned to confirm the efficacy and safety of
GSK1605786A 500 mg once daily and to establish the benefit-to-risk profile of
this dose in the treatment of active Crohn*s disease. In addition, this study
will also assess if a higher dose of 500 mg twice daily that delivers greater
plasma exposure can optimise the benefit-to-risk profile.
Study objective
Primary: to assess the efficacy of GSK1605786A compared with placebo as an
induction therapy in subjects with moderately-to-severely active Crohn*s
disease over 12 weeks. Secondary: Safety, quality of life, healthcare resource
utilisation, PK, genetic variants versus efficacy and safety.
Study design
Multicenter randomized double blind phase III parallel group study.
Randomisation (1:1) to treatment with:
1. GSK1605786A 500 mg once daily.
2. GSK1605786A 500 mg twice daily.
3. Placebo.
Plus background therapy (not part of study treatment, on prescription), to be
chosen by investigator.
Treatment duration 12 weeks.
Approx 600 patients.
Patients achieving remission during this study are eligible for a double blind
randomized placebo controlled follow-up study (CCX114157).
Intervention
Treatment with GSK1605786A or placebo.
Study burden and risks
Risk: Adverse effects of study medication.
Burden: 9 visits in 12 weeks. Duration 0,5-4 h.
Blood tests 9x (approx.50 ml in total), 5 PK samples at different time points
(during 1 visit or divided over several visits), pregnancy test (if relevant)
6x, stool investigation 2x, ECG 2x. Questionnaires (EQ 5D, SF-36, IBDQ,WPI-CD)
3x.
During screening daily phone call to answer some questions about the abdominal
symtoms. Also during the 8 days preceding visits 4, 6 and 8. Time consumption
5 min/day.
Coloscopy only if not performed during the past 12 months or in case blood and
stool tests do not prove moderately to severely active disease. Extra visit
necessary.
Huis ter Heideweg 62
3705 LZ Zeist
NL
Huis ter Heideweg 62
3705 LZ Zeist
NL
Listed location countries
Age
Inclusion criteria
* Subjects with Crohn*s disease since > 4 months (small bowel and/or colonic involvement). Confirmed <12 months ago (e.g. endoscopy, capsule endoscopy, MRI or barium X-ray).
* *18 years of age.
* CDAI score of *220 to *450 at Baseline.
* Confirmation of current active Crohn*s disease by either of the following: luminal ulceration visualised by screening endoscopy or elevated CRP (>ULN) plus elevated faecal calprotectin (> 200 *g/g stool) at screening.
* History of inadequate response and/or intolerance leading to discontinuation of at least one of the following treatments for Crohn*s disease: corticosteroids, immunosuppressants.
* Stable doses of permitted concomitant medications or having previously received, but are not currently receiving, medications for Crohn*s disease.
* 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 suspected small bowel stricture
* Enterocutaneous, abdominal or pelvic fistulae with abscesses or fistulae likely to require surgery during the study period.
* Bowel surgery, other than appendectomy, within 12 weeks prior to screen.
* 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 | EUCTR2010-022382-10-NL |
| CCMO | NL34539.018.10 |