A Randomised, Double-blind, Active Treatment Study to Induce Clinical Response and/or Remission with GSK1605786A in Subjects with Moderately-to-Severely Active Crohn*s Disease

Phase 3

Completed

Conditions: chronic inflammation of the digestive tract
Crohn's disease
10017969

Registration Number: NL-OMON39870

Lead Sponsor: GlaxoSmithKline

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 56

Inclusion Criteria

Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Male or female subjects aged *18 years
2. Written informed consent prior to any of the screening procedures including discontinuation of prohibited medications
3. Crohn*s disease for >4 months duration, which has been confirmed by diagnosis prior to study entry, with small bowel and/or colonic involvement
4. Current evidence of moderately-to-severely active disease defined by a CDAI score of *220**450 at baseline (Week 0)
5. Confirmation of active disease by
i. Elevated CRP (*3mg/L, the upper limit of normal (ULN) for the highly sensitive CRP test) at screening or
ii. Elevated levels of faecal calprotectin (>200*g/g stool) at Screening or
iii. Ileocolonscopy with documentation of a minimum of 3 nonanastomotic ulcerations(each > 5 mm in diameter) consistent with CD, within 3 months prior to Screening.
6. History of inadequate response and/or intolerance/adverse event leading to discontinuation of at least one of the following treatments for Crohn*s disease: corticosteroids or immunosuppressants
7. Stable doses of permitted concomitant medications or having previously received, but are not currently receiving, medications for Crohn*s disease. The number of subjects who have received treatment in the past with an anti-TNF for Crohn*s disease and discontinued due to loss or lack of efficacy will be limited to 50% of
those randomised.
8. Demonstrated ability to comply with Crohn*s disease symptom recording using the IVRS.

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:
1 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 coeliac disease (elevated anti-tissue transglutaminase antibodies)
2 Diagnosis of ulcerative or indeterminate colitis
3 Fistulae with abscesses, or fistulae likely to require surgery during the course of the study period
4 Bowel surgery, other than appendectomy, within 12 weeks prior to screening and/or has planned surgery or deemed likely to need surgery for CD during the study period
5 Extensive colonic resection, subtotal or total colectomy
6 Presence of ileostomies, colostomies or rectal pouches
7 Fixed symptomatic stenoses of small bowel or colon
8 Diagnosis of short bowel syndrome or chronic diarrhoea related to malabsorption and/or multiple bowel re-sections for Chron's disease
9 Chronic use of narcotics for chronic pain defined as daily use of one or more doses of narcotic containing medications
10 Use of prohibited medications, within their specified timeframes and throughout the study.
11 Positive immunoassay for C. difficile
12 Known HIV infection
13 Known varicella, herpes zoster, or other severe viral infection within 6 weeks of screening
14 Subjects who have received immunisation with a live vaccine e.g. measles, mumps, rubella (each as in MMR vaccine), oral polio, varicella, yellow fever, within 4 weeks of screening and throughout the study, with the exception of influenza vaccine
15 Confirmed positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) test or positive Hepatitis C test result
16 Confirmed positive result for QuantiFERON TB Gold test.
17 Current sepsis or infections requiring intravenous antibiotic therapy > 2 weeks
18 Previous infections characterised by opportunistic pathogens, and/or dissemination suggestive of clinically significant immunocompromise
19 The subject exhibits evidence of hepatic dysfunction, viral hepatitis, or exhibits serum ALT (SGPT) and/or AST (SGOT) values *2 times the upper limit of normal; has a total bilirubin value >1.5 times the upper limit of normal (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%); has alkaline phosphatase >1.5 times the upper limit of normal; has current or chronic history of liver disease including non-alcoholic steatohepatitis (NASH); has known hepatic or biliary abnormalities with the exception of Gilbert*s syndrome or asymptomatic gallstones
20 QTc *450 msec (*480msec for those with Bundle Branch Block)
21 Congenital or acquired immunodeficiency or has evidence of immunocompromise manifested by current opportunistic infection
22 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)
23 History of evidence of adenomatous colonic polyps that have not been removed.
24 History of evidence of colonic mucosal dysplasia
25 If female, is pregnant, has a positive pregnancy test or is breast-feeding
26 Concurrent illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study
27 Medical history of sensitivity to any of the

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Proportion of subjects achieving clinical response, defined by CDAI decrease<br /><br>from baseline of *100 points, at Week 12.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. Proportion of subjects in clinical remission, defined as a CDAI score of <150<br /><br>points, at Week 12.<br /><br>2. Proportion of subjects with a clinical response (CDAI decrease from baseline<br /><br>of<br /><br>100 points) at both Week 8 and Week 12.<br /><br>3. Proportion achieving clinical remission (CDAI <150 points) at both Week 8 and<br /><br>Week 12.<br /><br>4. Proportion of subjects with a clinical response (CDAI decrease from baseline<br /><br>of<br /><br>100 points) at Week 8.<br /><br>5. Proportion achieving clinical remission (CDAI <150 points) at Week 8.</p><br>