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This is a randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of two doses (500 mg once daily and 500 mg twice daily) of GSK1605786A as compared to placebo over 12 weeks in adult subjects with moderately-to-severely active Crohn's disease. Efficacy will be assessed by proportion of subjects achieving response, defined as a decrease in Crohn's Disease Activity Index (CDAI) score of at least 100 points (clinical response). Clinical remission (CDAI score less than 150 points) will be evaluated as a key secondary endpoint. Safety will be assessed by recording of adverse events, clinical laboratory parameters, vital signs and electrocardiogram (ECG). Population pharmacokinetics will evaluate the two doses of GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire (IBDQ), Short Form-36 version 2 (SF-36v2), EQ-5D and Work Productivity and Activity Impairment-CD (WPAI-CD) and receipt of disability.
Full description
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.
Enrollment
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Inclusion criteria
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
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
Primary purpose
Allocation
Interventional model
Masking
608 participants in 3 patient groups, including a placebo group
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Data sourced from clinicaltrials.gov
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