E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with Moderately-to-Severely Active Crohn’s Disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the efficacy of GSK1605786A compared with placebo as an induction therapy in subjects with moderately-to-severely active Crohn’s disease over 12 weeks. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of GSK1605786A compared with placebo in subjects with moderately-to-severely active Crohn’s disease • To investigate the effect of GSK1605786A compared with placebo on health related quality of life in subjects with moderately-to-severely active Crohn’s disease • To investigate the effect of GSK1605786A compared with placebo on healthcare related resource utilisation in subjects with moderately-to-severely active Crohn’s disease • To explore the dose relationships between GSK1605786A plasma concentration and clinical response endpoints • To explore potential relationships between genetic variants and GSK1605786A efficacy and safety endpoints. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (>ULN) plus elevated faecal calprotectin (> 200 μg/g stool) at Screening Note: Subjects who fail to meet criterion 7b) may qualify if criterion 7a) is met. If 7b) is met and investigator elects to perform an endoscopy within the screening period which is subsequently adjudicated as negative, then the subject is excluded. 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. Female subjects: To be eligible, 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 < 1% for the duration of this study as defined by the following: Abstinence Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Contraceptive Methods with a Failure Rate of < 1% • Oral contraceptive, either combined or progestogen alone • Injectable progestogen • Implants of 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 sterilisation (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, “documented” refers to the outcome of the investigator's/designee’s medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records. • Double barrier method: condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring subjects understand how to properly use these methods of contraception. • A serum pregnancy test is required of all females of child-bearing potential. In addition, a urine pregnancy test will be performed on the morning of randomisation visit (Week 0) and at Weeks 4, 8 and 12. Country specific inclusion criterion for subjects in France: A subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
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E.4 | Principal 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. Known or suspected small bowel stricture 5. Enterocutaneous, abdominal or pelvic fistulae with abscesses or fistulae likely to require surgery during the study period 6. 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 7. Extensive colonic resection, subtotal or total colectomy 8. Presence of ileostomies, colostomies or rectal pouches 9. Known fixed symptomatic stenoses 10. History of more than 3 small bowel resections or diagnosis of short bowel syndrome 11. Chronic use of narcotics for chronic pain defined as daily use of one or more doses of narcotic containing medication 12. Use of prohibited medications, including enteral feeding or elemental diet, within their specified timeframes (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 8 weeks prior to screening • 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 • Intravenous antibiotic use: Use of intravenous antibiotics for Crohn’s disease within 4 weeks prior to screening • Use of rectal treatment with 5-ASA or corticosteroid enemas/suppositories within 2 weeks prior to screening • Use of tube or enteral feeding, elemental diet, or parenteral alimentation within 2 weeks prior to screening • Leukocytapheresis or granulocytapheresis within 2 weeks prior to screening 13. Positive immunoassay for C. difficile [Subjects who test positive and receive antibiotic treatment may be re-screened after 4 months the re-test is negative] 14. Known HIV infection 15. Known varicella, herpes zoster, or other severe viral infection within 6 weeks of screening 16. 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, with the exception of influenza vaccine 17. Active or latent tuberculosis (TB) infection: All subjects will be tested with QuantiFERON TB Gold test and those with positive test result will be excluded. View protocol for further information. 18. Current sepsis or infections requiring intravenous antibiotic therapy >2 weeks 19. Previous infections characterised by opportunistic pathogens, and/or dissemination suggestive of clinically significant immunocompromise 20. The subject has congenital or acquired immunodeficiency or has evidence of immunocompromise manifested by current opportunistic infection. 21. The subject exhibits evidence of hepatic dysfunction, viral hepatitis or increases in ALT(SGPT)/AST(SGOT)/alkaline phosphase/bilirubin above pre-defined thresholds. See protocol for further information. 22. A positive HBsAg or Anti-HBc test or positive Hepatitis C antibody result at screening 23. QTc ≥450 msec (480 msec for those with Bundle Branch Block) 24. The subject has a concurrent illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study (e.g., an unstable cardiovascular, autoimmune, renal, hepatic, pulmonary, endocrine, metabolic, gastrointestinal, haematologic, or neurological condition or mental impairment) 25. History or evidence of adenomatous colonic polyps that have not been removed 26. History of evidence of colonic mucosal dysplasia 27. The subject has 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) 28. Any previous participation in a clinical study of GSK1605786A (formerly ChemoCentryx compound CCX282-B) 29. Medical history of sensitivity to any of the components of GSK1605786A (microcrystalline cellulose, crospovidone, sodium stearyl fumarate). 30. Use of any investigational product within 30 days prior to screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion of subjects achieving clinical response, defined by CDAI decrease from baseline of ≥100 points, at Week 12 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |