A Randomised, Double-blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of GSK1605786A in the Treatment of Subjects with Moderately-to Severely Active Crohn’s Disease
- Conditions
- Subjects with Moderately-to-Severely Active Crohn’s DiseaseMedDRA version: 12.1Level: LLTClassification code 10011401Term: Crohn's disease
- Registration Number
- EUCTR2010-022382-10-NL
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
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 oc
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 interp
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method