A Study to Investigate the Efficacy and Safety of GSK1605786A in the Treatment of Subjects With Moderately-to-Severely Active Crohn's Disease

This is a multi-centre, randomised, double-blind, placebo-controlled, parallel group study
to evaluate the efficacy of two oral doses of GSK1605786A (500 mg once daily, 500 mg twice
daily) as compared to placebo in the induction of clinical response over a 12-week treatment
period in subjects with moderately-to-severely active Crohn's disease. Secondary objectives
will include assessment of the safety and evaluation of the efficacy in induction of
remission.

The study is planned to randomise approximately 600 subjects (200 subjects/group) with
active Crohn's disease, diagnosed for at least 4 months with a documented history of disease
in the small and/or large intestine, and characterised by a Crohn's Disease Activity Index
(CDAI) score between 220 to and 450, inclusive. Subjects must have reported an inadequate
response or intolerance to Crohn's disease treatment with corticosteroids or
immunosuppressants. Inclusion of subjects who received prior treatment with a biologic
anti-tumour necrosis factor (TNF) agent will be limited to approximately 50% of the study
population. All subjects are required to have a diagnosis with identification of anatomic
location of Crohn's disease, which has been established by visualisation of the
gastrointestinal tract within 12 months of screening. Subjects who have not had a
visualisation of the gastrointestinal tract within 12 months are required to undergo an
endoscopic assessment during the screening period. Subjects will be required to have
evidence of current active inflammation at the time of randomisation either by endoscopy or
by inflammatory biomarkers [elevated C-reactive protein (CRP) greater than the upper limit
of normal (ULN) plus a positive faecal calprotectin test]. Subjects who do not meet the
requirements based on inflammatory biomarker test results will be required to qualify based
on endoscopic assessment during screening. Subjects will be allowed to participate in the
study while continuing on stable doses of agents typically used to treat Crohn's disease.
Following the screening period, subjects will be randomised at baseline to receive blinded
treatment with one of two doses of GSK1605786A (500 mg once daily or twice daily) or placebo
for 12 weeks. Response and remission endpoints, using the CDAI, will be evaluated at Weeks
4, 8 and 12.

Inclusion Criteria:

- Male or female subjects aged 18 years or older

- Written informed consent

- Diagnosis of Crohn's disease for greater than 4 months duration with small bowel
and/or colonic involvement

- Confirmation of Crohn's disease established by visualisation of the gastrointestinal
tract within the 12 months prior to screening or by screening endoscopy at study
entry

- History of inadequate response and/or intolerance/adverse event leading to
discontinuation of either corticosteroids or immunosuppressants

- Moderately-to-severely active disease characterised by a CDAI score between 220 and
450, inclusive, at Baseline

- Confirmation of current active Crohn's disease by screening endoscopy or inflammatory
biomarkers [elevated C-reactive protein (greater than upper limit of normal) plus
positive test for faecal calprotectin] at Screening

- Stable doses of permitted concomitant medications or having previously received, but
are not currently receiving, medications for Crohn's disease

- Demonstrated ability to comply with Crohn's disease symptom recording using the
interactive voice response system

- Females of child-bearing potential must be sexually inactive or commit to consistent
and correct use of a contraceptive method of birth control with a failure rate of
less than 1% for the duration of this study

Exclusion Criteria:

- If female: pregnant, has a positive pregnancy test or is breast-feeding

- Diagnosis of coeliac disease, follow a gluten-free diet to manage symptoms, or
positive test for coeliac disease

- Diagnosis of ulcerative or indeterminate colitis

- 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 and/or has
surgery planned or deemed likely for Crohn's disease during the study period

- Extensive colonic resection, subtotal or total colectomy

- Presence of ileostomies, colostomies or rectal pouches

- Known fixed symptomatic stenoses

- History of more than 3 small bowel resections or diagnosis of short bowel syndrome

- Chronic use of narcotics for chronic pain defined as daily use of one or more doses
of narcotic containing medication

- Use of prohibited medications, including enteral feeding or elemental diet, within
their specified time frames

1. Biologic use: Use of any biologic (tumour necrosis factor inhibitor or
natalizumab) within 8 weeks prior to screening

2. Corticosteroid use: Use of parenteral glucocorticoids within 4 weeks prior to
screening

3. Immunospressant use: Use of cyclosporine, tacrolimus, sirolimus or mycophenolate
mofetil within 4 weeks prior to screening

4. Intravenous antibiotic use: Use of intravenous antibiotics for Crohn's disease
within 4 weeks prior to screening

5. Use of rectal treatment with 5-ASA or corticosteroid enemas/suppositories within
2 weeks prior to screening

6. Use of tube or enteral feeding, elemental diet, or parenteral alimentation
within 2 weeks prior to screening

7. Leukocytapheresis or granulocytapheresis within 2 weeks prior to screening

- Positive immunoassay for Clostridium difficile

- Known human immunodeficiency virus (HIV) infection

- Known varicella, herpes zoster, or other severe viral infection within 6 weeks of
screening

- Immunisation with a live vaccine within 4 weeks of screening, with the exception of
influenza vaccine

- Active or latent tuberculosis infection

- Current sepsis or infections requiring intravenous antibiotic therapy for more than 2
weeks

- Evidence of hepatic dysfunction, viral hepatitis, or current or chronic history of
liver disease including non-alcoholic steatohepatitis (NASH)

- Positive test for Hepatitis B or Hepatitis C antibody at screening

- Corrected QT interval of ECG (electrocardiogram) greater than or equal to 450
milliseconds

- Concurrent illness or disability that may affect the interpretation of clinical data,
or otherwise contraindicates participation in this clinical study

- History or evidence of adenomatous colonic polyps that have not been removed

- History of evidence of colonic mucosal dysplasia

- Current evidence of, or has been treated for a malignancy within the past five years
(other than localised basal cell, squamous cell skin cancer, cervical dysplasia, or
any cancer in situ that has been resected)

- Any previous participation in a clinical study of GSK1605786A (formerly ChemoCentryx
compound CCX282-B)

- Medical history of sensitivity to any of the components of GSK1605786A

- Use of any investigational product within 30 days prior to screening