E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with Crohn’s Disease |
|
E.1.1.1 | Medical condition in easily understood language |
Crohn’s disease Inflammatory bowel disease
|
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
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 safety and tolerability of long-term treatment with GSK1605786A in subjects with Crohn’s disease. |
|
E.2.2 | Secondary objectives of the trial |
• To assess the effectiveness of long-term treatment with GSK1605786A
• To assess changes in health-related quality of life
• To assess changes in healthcare-related resource utilisation
• To assess changes in work productivity and activity impairment
• To assess changes in unemployment and disability rates
• To assess changes in C-reactive protein (CRP) as a biomarker of
inflammation
• To potentially evaluate the correlation of genetic markers with the safety and effectiveness of GSK1605786A. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Previous participation in a GSK-sponsored study with GSK1605786A as follows:
a. completion of the placebo-controlled induction study, CCX114151, without achieving clinical response (CDAI => 100 point decrease) or clinical remission (CDAI < 150) at Week 12 or completion of other GSK-sponsored induction studies, with the exception of Study CCX114643, as designated by the sponsor
b. completion of maintenance study CCX114157 at Week 52
c. withdrawal from maintenance study CCX114157 due to worsening of Crohn’s disease and requiring a treatment change
2. Written informed consent prior to any CCX114644-specific study procedures
3. 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 interview with the subject on his medical history.
• Male condom combined with a vaginal spermicide (foam, gel, film,
cream, or suppository)
• Male condom combined with a female diaphragm, either with or
without a vaginal spermicide (foam, gel, film, cream, or 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. This list does not apply to FCBP with same sex partners, when this is their preferred and usual lifestyle. |
|
E.4 | Principal exclusion criteria |
1. If female, is pregnant, has a positive pregnancy test or is breast-feeding, or is planning to become pregnant
2. Subjects with known or suspected coeliac disease or a positive screening test for antitissue transglutaminase (anti-tTG) antibodies) should have been excluded from enrolment into the induction studies. Subjects in whom a diagnosis of coeliac disease is subsequently suspected should be tested for anti-tTG antibodies and excluded or withdrawn from study upon positive test result.
3. Fixed symptomatic stenoses of small bowel or colon
4. Enterocutaneous, abdominal or pelvic fistulae likely to require surgery during the study period
5. Current sepsis or infections requiring intravenous antibiotic therapy >2 weeks
6. Use of prohibited medications at baseline and throughout the study (Section 5.4.2 of the protocol - Prohibited Medications and Non Drug Therapies)
7. The subject exhibits evidence of hepatic dysfunction or viral hepatitis;has serum
ALT (SGPT) and/or AST (SGOT) values ≥2 times the upper limit ofnormal, 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 <35%), oralkaline
phosphatase >1.5 times the upper limit of normal; has current or chronic history of
liver disease including non-alcoholic steatohepatitis (NASH); or has
known hepatic or biliary abnormalities with the exception of Gilbert's syndrome or asymptomatic gallstones8. Subjects who have demonstrated safety or tolerability issues during participation in a previous study with GSK1605786A which, in the opinion of the Investigator, was possibly related to study treatment and poses an unacceptable risk to the subject. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety Primary Endpoints:
Incidence of adverse events/Serious adverse events |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety assessments at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and post 4 week follow-up at Week 112.
12 lead ECG at Week 0, 24, 48, 72, 108 and post 4 week follow-up at Week 112.
CDAI assessments at Week 0, 12, 24, 36, 48, 60, 72, 84, 96 108 and post 4 week follow-up at Week 112.
|
|
E.5.2 | Secondary end point(s) |
• 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. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety assessments at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and post 4 week follow-up at Week 112.
12 lead ECG at Week 0, 24, 48, 72, 108 and post 4 week follow-up at Week 112.
CDAI assessments at Week 0, 12, 24, 36, 48, 60, 72, 84, 96 108 and post 4 week follow-up at Week 112.
|
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.5.1 | Number of sites anticipated in the EEA | 154 |
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 | No |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
China |
Czech Republic |
Denmark |
Estonia |
France |
Germany |
Greece |
Hong Kong |
Hungary |
Ireland |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
New Zealand |
Norway |
Poland |
Portugal |
Russian Federation |
Slovakia |
Spain |
Sweden |
Switzerland |
Taiwan |
Ukraine |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |