A Randomised, Double-blind, Active Treatment Study to Induce Clinical Response and/or Remission with GSK1605786A in Subjects with Moderately-to-Severely Active Crohn’s Disease

• Register: EUCTR
• Last refreshed on: 23 September 2013
• Main ID: EUCTR2011-002817-12-HU
• Date of registration: 06/11/2012
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research and Development Limited
• Public title: A Randomised, Double-blind, Active Treatment Study to Induce Clinical Response and/or Remission with GSK1605786A in Subjects with Moderately-to-Severely Active Crohn’s Disease
• Scientific title: A Randomised, Double-blind, Active Treatment Study to Induce Clinical Response and/or Remission with GSK1605786A in Subjects with Moderately-to-Severely Active Crohn’s Disease
• Date of first enrolment: 13/12/2012
• Target sample size: 900
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002817-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no 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: no Other: yes Other specify the comparator: Different doses of IMP (500 mg once daily vs 500 mg twice daily) Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, 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, South Africa, Spain, Sweden, Switzerland, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trials HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Ltd.

• Name: Clinical Trials HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for enrolment in the study must meet all of the following 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. Crohn's disease for >4 months duration, which has been confirmed by diagnosis prior to study entry, with small bowel and/or colonic involvement
4. Current evidence of moderately-to-severely active disease defined by a CDAI score of =220–=450 at baseline (Week 0)
5. Confirmation of active disease by i. Elevated CRP (=3mg/L, the upper limit of normal (ULN) for the highly sensitive CRP test) at screening or ii. Elevated levels of faecal calprotectin (>200µg/g stool) at Screening or iii. Ileocolonoscopy with documentation of a minimum of 3 nonanastomotic ulcerations+ (each > 5mm in diameter) consistent with CD, within 3 months prior to Screening
6. 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 or immunosuppressants
7. Stable doses of permitted concomitant medications +++ or having previously received, but are not currently receiving, medications for Crohn's disease. The number of subjects who have received treatment in the past with an anti-TNF for Crohn's disease and discontinued due to loss or lack of efficacy will be limited to ~50% of those randomised.
8. Demonstrated ability to comply with Crohn's disease symptom recording using the IVRS.
9. Female subjects of child-bearing potential (FCBP) are eligible if she is:
a) Not pregnant or nursing
b) Committed 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 and, if applicable, the follow-on maintenance study, CCX114157, 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 sterilisation prior to the female subject's entry into the study, and this male is the sole partner for that subject.
• 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.

+ Aphthous ulcerations are not sufficient for confirmation of disease activity. Ileocolonoscopy must be prior to study entry and is not included as a study-related procedure.
++Based on the subject's medical history, the investigator will make the determination of the reason for discontinuation and will record this information in the eCRF.
+++Refer to Section 5.6.1 Concomi
Exclusion criteria:
Subjects meeting any of the following criteria must not be enrolled in the study:
1 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)
2 Diagnosis of ulcerative or indeterminate colitis
3 Fistulae with abscesses or fistulae likely to require surgery during the course of the study period
4 Bowel surgery, other than appendectomy, within 12 weeks prior to screening and/or has planned surgery or deemed likely to need surgery for CD during the study period
5 Extensive colonic resection, subtotal or total colectomy
6 Presence of ileostomies, colostomies or rectal pouches
7 Fixed symptomatic stenoses of small bowel or colon
8 Diagnosis of short bowel syndrome or chronic diarrhoea related to malabsorption and/or multiple bowel re-sections for Crohn's disease
9 Chronic use of narcotics for chronic pain defined as daily use of one or more doses of narcotic containing medications
10 Use of prohibited medications within their specified timeframes and throughout the study
• Biologic use: Use of any biologic, including investigational agents for the treatment of Crohn's disease within 10 weeks prior to Randomisation. Prohibited agents include but are not limited to any TNF inhibitor (infliximab, adalimumab or certolizumab) or natalizumab, vedolizumab, and ustekinumab.
• Corticosteroid use: Use of parenteral glucocorticoids within 4 weeks prior to Screening
• Immunospressant use: Use of cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil or any other immunosuppressant agent not specified in permitted medications within 4 weeks prior to Screening
• Enteral feeding: Start of enteral feeding (any composition) for the treatment of Crohn's disease activity within 4 weeks prior to screening
**
• Rectal Treatment: Use of 5-ASA or corticosteroid
enemas/suppositories within 2 weeks prior to Screening
• Leukocytapheresis or granulocytapheresis within 2 weeks prior to Screening.
• Paracetamol/acetaminophen > 2 g/day throughout the study.
• Opioid analgesics for worsening Crohn's disease pain are prohibited when used on a regular daily basis for more than 3 days.
• Digoxin or related cardiac glycosides use within 7 days prior to
Screening
• Any previous participation in a clinical study of GSK1605786A
(formerly ChemoCentryx compound CCX282-B)
11 Positive immunoassay for C. difficile
12 Known HIV infection
13 Known varicella, herpes zoster, or other severe viral infection within 6 weeks of screening
14 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
15 Confirmed positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) test or confirmed positive hepatitis C test result***
16 Confirmed positive result for QuantiFERON TB Gold test***
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 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

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

Health Condition(s) or Problem(s) studied

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

Moderately-to-Severely Active Crohn’s Disease
MedDRA version: 16.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

Intervention(s)

Product Name: GSK1605786A
Product Code: GSK1605786A
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: GSK1605786A
Current Sponsor code: GSK1605786A
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: In subjects with moderately-to-severely active Crohn’s disease:
• To assess induction of response with two doses of GSK1605786A over 12 weeks.
• To assess induction of remission with two doses of GSK1605786A over 12 weeks.
• To evaluate the safety of GSK1605786A over a 12-week treatment period.
• To investigate the effect of GSK1605786A on biomarkers of inflammation [C-reactive protein (CRP) and faecal calprotectin].
• 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.

Main Objective: To induce clinical response (CDAI decrease from baseline = 100 points) and/or remission (CDAI <150) following 12 weeks of treatment with one of two active doses of GSK1605786A for qualification of subjects for enrolment into a follow-on 52-week maintenance study (CCX114157).

Timepoint(s) of evaluation of this end point: Week 12

Primary end point(s): Proportion of subjects achieving clinical response, defined by CDAI decrease from baseline of =100 points, at Week 12.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Weeks 8 and 12.

Secondary end point(s): 1. Proportion of subjects in clinical remission, defined as a CDAI score of <150 points, at Week 12.
2. Proportion of subjects with a clinical response (CDAI decrease from baseline of =100 points) at both Week 8 and Week 12.
3. Proportion achieving clinical remission (CDAI <150 points) at both Week 8 and Week 12.
4. Proportion of subjects with a clinical response (CDAI decrease from baseline of =100 points) at Week 8.
5. Proportion achieving clinical remission (CDAI <150 points) at Week 8.
6. Change from baseline in CRP concentration at Week 12.
7. Change from baseline in faecal calprotectin concentration at Week 12.

Secondary ID(s)

CCX114643

2011-002817-12-GR

Source(s) of Monetary Support

GlaxoSmithKline Research and Development Limited