An Open-Label Extension Study to Assess the Safety of GSK1605786A in Subjects with Crohn*s Disease (CCX114644)

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.
This study addresses primarily the longterm safety and tolerability of
GSK1605786A (500 mg twice daily) in subjects with Crohn*s disease.

Primary: Safety and tolerability. Secondary: Effectiveness, quality of life,
healthcare resource utilisation, work productivity.

Multicenter open label non comparative phase III study.
Treatment with GSK1605786A 500 mg twice daily.
Plus background therapy (not part of study treatment, on prescription.
Treatment duration 2 years. Once the results of the induction study CCX114151
(see below) are known, the risk-to-benefit ratio will be re-assessed and the
study may be extended to allow continued treatment up to the anticipated launch
and availability of GSK1605786A.
Approx 800 patients.
Patients having participated in several preceding studies with GSK1605786A are
eligible for this follow-up study.
This follow-up study has been submitted for approval at the same time. The same
applies to the previous study CCX114151. For the Netherlands are of interest
the induction study CCX114151 and the longterm efficacy study CCX114157. Both
have a double blind randomized placebo controlled design. Two dosages of
GSK1605786A are tested: 500 mg once and twice daily.
Subjects will enter the study via one of three routes: completion of the
placebo-controlled induction study, CCX114151, without achieving clinical
response or remission, completion of maintenance study CCX114157, withdrawal
from maintenance study CCX114157 due to worsening of Crohn*s disease.

Treatment with GSK1605786A.

Risk: Adverse effects of study medication.
Burden: 23 visits in 2 years. Duration 0,5-1,5 h.
Blood tests 23x (approx.165 ml in total), pregnancy test (if relevant) 14x, ECG
6x. Questionnaires (EQ 5D, SF-36, IBDQ,WPI-CD) 4x.
Daily phone call to answer some questions about the abdominal symtoms during
the 8 days preceding 11 visits Time consumption 5 min/day.