Subjects with Moderately-to-Severely Active Crohn’s Disease MedDRA version: 14.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: GSK1605786A
Product Code: GSK1605786A
Pharmaceutical Form: Capsule, hard
Current Sponsor code: GSK1605786A
Concentration u
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion 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. A diagnosis of Crohn’s disease for > 4 months duration with small bowel and/or colonic involvement 4. 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. Acceptable methods for gastrointestinal tract visualisation include, but are not limited to endoscopy, capsule endoscopy, MRI or barium X-ray. Subjects without visualisation of the gastrointestinal tract within 12 months of screening must be willing to undergo endoscopy within the screening period 5. 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, immunosuppressants 6. Current evidence of moderately-to-severely active disease characterised by a CDAI score of =220 to =450 at Baseline (Week 0) [Criterion for Randomisation] 7. Confirmation of current active Crohn’s disease by either of the following [Criterion for Randomisation]: a. Luminal ulceration visualised by Screening endoscopy and as adjudicated by central endoscopy reader, or b. Elevated CRP (= 3 mg/L, the upper limit of normal (ULN) for the highly sensitive CRP test) plus elevated faecal calprotectin (> 200 µg/g stool) at Screening 8. Stable doses of permitted concomitant medications or having previously received, but are not currently receiving, medications for Crohn’s disease. Please refer to Section 5.5.1 Permitted Medications and Non Drug Therapies. 9. Demonstrated ability to comply with Crohn’s disease symptom recording using the IVRS; to be eligible for randomisation subject must complete recording of symptoms for at least 8 consecutive days prior to the randomisation/baseline visit (Week 0). 10. Females of child-bearing potential (FCBP) must be sexually inactive or commit to use of contraceptive methods with a failure rate of < 1% per year when used consistently and correctly and, when applicable, in accordance with the product label, for the duration of this study as defined by the following: Contraceptive Methods with a Failure Rate of < 1% • Abstinence from penile-vaginal intercourse, when this is the female’s preferred and usual lifestyle • Oral contraceptive, either combined or progestogen alone • Injectable progestogen • Implants of etonogestrel or levonorgestrel • Estrogenic vaginal ring • Percutaneous contraceptive patches • Intrauterine device (IUD) or intrauterine system (IUS) that meets the <1% failure rate as stated in the product label • Male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject. The information on the male sterility can come from the site personnel’s: review of subject’s medical records; medical examination of the subject and/or semen analysis; or in
Exclusion criteria
Exclusion criteria: 1. If female, is pregnant, has a positive pregnancy test or is breast-feeding 2. 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) 3. Diagnosis of ulcerative or indeterminate colitis 4. Enterocutaneous, abdominal or pelvic fistulae with abscesses or fistulae likely to require surgery during the study period 5. Bowel surgery, other than appendectomy, within 12 weeks prior to screen and/or has surgery planned or deemed likely for CD during the study period 6. Extensive colonic resection, subtotal or total colectomy 7. Presence of ileostomies, colostomies or rectal pouches 8. Fixed symptomatic stenoses of small bowel or colon 9. History of more than 3 small bowel resections or diagnosis of short bowel syndrome 10. Chronic use of narcotics for chronic pain defined as daily use of one or more doses of narcotic containing medication 11. Use of prohibited medications, including enteral feeding or elemental diet, within their specified timeframes and throughout the study (Section 5.5.2 Prohibited Medications and Non Drug Therapies). Biologic use: Use of any TNF inhibitor (eg. infliximab, adalimumab or certolizumab) or natalizumab within 10 weeks prior to randomisation Corticosteroid use: Use of parenteral glucocorticoids within 4 weeks prior to screening Immunospressant use: Use of cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil within 4 weeks prior to screening. For further information please view protocol pages 31-32 12. Positive immunoassay for C. difficile [Subjects who test positive and receive antibiotic treatment may be re-screened after 4 months if the re-test is negative] 13. Known HIV infection 14. Known varicella, herpes zoster, or other severe viral infection within 6 weeks of screening 15. 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 16. Active or latent tuberculosis (TB) infection: All subjects will be tested with QuantiFERON TB Gold test and those with a positive test result will be excluded. Please view protocol page 31 for further information. 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 has congenital or acquired immunodeficiency or has evidence of immunocompromise manifested by current opportunistic infection 20. 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 1.5 times the upper limit of normal; has curren
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the efficacy of GSK1605786 compared with placebo as an induction therapy in subjects with moderately-to-severely active Crohn’s disease over 12 weeks. ; Secondary Objective: • To evaluate the safety of GSK1605786 compared with placebo • To investigate the effect of GSK1605786 compared with placebo on health related quality of life • To investigate the effect of GSK1605786 compared with placebo on healthcare related resource utilisation • To investigate the effect of GSK1605786 compared with placebo on work productivity and activity impairment • To investigate the effect of GSK1605786 compared with placebo on biomarkers of inflammation [C-reactive protein (CRP) and faecal calprotectin] • To explore the dose relationships between GSK1605786 plasma concentration and clinical response endpoints • To explore potential relationships between genetic variants and GSK1605786 efficacy and safety endpoints. ; Primary end point(s): • Proportion of subjects achieving clinical response, defined by CDAI decrease from baseline of =100 points, at Week 12 Safety Endpoints: • Incidence of adverse events/serious adverse events • Change from baseline in vital signs: heart rate and blood pressure • Change from baseline in haematology and clinical chemistry parameters • Change from baseline in liver function test parameters • Change from baseline in 12 lead ECG abnormalities. ; Timepoint(s) of evaluation of this end point: Safety assessments at Week 0, 4, 8, 12 and post 4 week follow-up at Week 16, if subject does not enrol in follow on study. 12 lead ECG at Screening and Week 12. CDAI assessments at Week 0, 4, 8, 12, and post 4 week follow-up at Week 16, if | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Endpoint: • Proportion of subjects in clinical remission, defined as a CDAI score of <150 points, at Week 12 ; Timepoint(s) of evaluation of this end point: Safety assessments at Week 0, 4, 8, 12 and post 4 week follow-up at Week 16, if subject does not enrol in follow on study. 12 lead ECG at Screening and Week 12. CDAI assessments at Week 0, 4, 8, 12, and post 4 week follow-up at Week 16, if subject does not enrol in follow on study. | — |
Countries
Australia, Austria, Belgium, Canada, Czech Republic, Denmark, France, Germany, Hungary, Italy, Japan, Netherlands, Norway, Slovakia, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClincial Trials HelpDesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed