A 52 week Randomised, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of GSK1605786A in the Maintenance of Remission in Subjects with Crohn’s Disease

• Register: EUCTR
• Last refreshed on: 12 May 2014
• Main ID: EUCTR2010-022383-12-NL
• Date of registration: 29/10/2010
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Limited
• Public title: A 52 week Randomised, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of GSK1605786A in the Maintenance of Remission in Subjects with Crohn’s Disease
• Scientific title: A 52 week Randomised, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of GSK1605786A in the Maintenance of Remission in Subjects with Crohn’s Disease
• Date of first enrolment: 16/02/2011
• Target sample size: 750
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022383-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Norway, Poland, Portugal, Russian Federation, Slovakia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Clincial Trials HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

• Name: Clincial Trials HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects achieving clinical response (CDAI decrease = 100points) and/or remission (CDAI <150) upon completion of treatment in Study CCX114151 or Study CCX114643
2. Written informed consent prior to any CCX114157 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.
Female subjects should not be enrolled if they are pregnant or lactating or if they plan to become pregnant during the time of study participation. For women of child-bearing potential, a urine pregnancy test will be performed at repeated intervals throughout the study and at the Early Withdrawal or Follow-up visits if applicable.
4. Any medications being currently received for Crohn’s disease must remain stable throughout the study period with the exception of tapering of corticosteroids and dose
reductions of immunosuppressants for the management of drug toxicity. See Study Procedures Manual.
5. Subjects on corticosteroids at entry must be willing to undergo corticosteroid dose tapering.
Note: Country-specific requirement for French 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.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion criteria:
1. If female, is pregnant, has a positive pregnancy test or is breast-feeding
2. Subjects with known or suspected coeliac disease or a positive screening test (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 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 5.5.3 of the protocol).
7. 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 <35%); has alkaline phosphatase >1.5 times the upper limit of normal; has current or chronic history of liver disease including non-alcoholic steatohepatitis (NASH); has known hepatic or biliary abnormalities with the exception of Gilbert’s syndrome or asymptomatic gallstones
Note: At randomisation into the study, liver function tests results from the final visit in the preceding induction study will not be available . Subjects who have abnormalities as per the exclusion above will need to be withdrawn.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Subjects with Crohn's Disease
MedDRA version: 16.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: GSK1605786A
Product Code: GSK1605786A
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: GSK1605786A
CAS Number: na
Current Sponsor code: GSK1605786A
Other descriptive name: na
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: • To evaluate the safety of GSK1605786A compared with placebo
• To investigate the effect of GSK1605786A compared with placebo on health-related quality of life
• To investigate the effect of GSK1605786A compared with placebo on health-related resource utilisation
• To investigate the effect of GSK1605786A compared with placebo on work productivity and activity impairment
• To investigate the effect of GSK1605786A compared with placebo on unemployment and disability rates
• To investigate the effect of GSK1605786A compared with placebo on biomarkers of inflammation [C-reactive protein (CRP) and faecal calprotectin]
• To explore the dose relationships between GSK1605786A plasma concentration and Clinical response endpoints

Timepoint(s) of evaluation of this end point: Safety assessments at Week 0, 4, 8, 12, 20, 28, 36, 44, 52
and post 4 week follow-up at Week 56, if subject does not enrol in follow on study.
12 lead ECG at Week 0, 28, 52 and post 4 week follow-up at Week 56, if subject does not enrol in follow on study.
CDAI assessments at Week 0, 4, 8, 12, 20, 28, 36, 44, 52 and post 4 week follow-up at Week 56, if subject does not enrol in follow on study.

Main Objective: • To assess the efficacy of GSK1605786A compared with placebo in maintaining
clinical remission in subjects with Crohn’s disease over 52 weeks.

Primary end point(s): Primary Efficacy endpoints:

Proportion of subjects in clinical remission (CDAI score <150 points) at both Weeks 28 and 52 of the 52-week treatment period

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

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Weeks 28 and 52

Secondary end point(s): Key Secondary efficacy endpoint:
Proportion of subjects in clinical remission (CDAI score <150 points) and not taking corticosteroids at both Weeks 28 and 52 of the 52-week treatment period

Secondary ID(s)

CCX114157

Source(s) of Monetary Support

GlaxoSmithKline Research & Development Ltd