A Study to Investigate the Efficacy and Safety of GSK1605786A in the Treatment of Subjects With Moderately-to-Severely Active Crohn's Disease
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Intervention: GSK1605786A; GSK1605786A; Placebo
Intervention description: 500 mg twice daily, administered orally for 12 weeks; 500 mg once daily, administered orally for 12 weeks; Placebo capsules, administered orally for 12 weeks
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 608.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Crohn's disease; capsule; GSK1605786A; quality of life; inflammatory bowel disease; oral therapy

Summary:

      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.
    

Eligibility criteria:

        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