A Phase II study to investigate GSK1605786 fo the treatment of patients with Ulcerative Colitis.

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2011-002818-37-BE
• Date of registration: 03/10/2011
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Ltd
• Public title: A Phase II study to investigate GSK1605786 fo the treatment of patients with Ulcerative Colitis.
• Scientific title: A phase II, 20-week, multi-centre, randomised, double-blind, placebo-controlled, parallel group proof of concept study to investigate the efficacy and safety of GSK1605786 for treatment of patients with active Ulcerative Colitis.
• Date of first enrolment: 15/02/2012
• Target sample size: 45
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002818-37
• 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: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Netherlands, United Kingdom

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:
1. Male or female aged 18 and over at the time of signing the informed consent.
2. A female subject of child-bearing potential is eligible to participate if she agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until completion of the follow-up visit.
3. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form, prior to any of the screening procedures including discontinuation of prohibited medication.
4. At screening (visit 1): patients with a clinical history and examination suggestive of active UC for at least 3 months despite at least 2 weeks treatment with oral >2.4g/day mesalazine / mesalamine or equivalent.
5. At screening/randomization (visit 2):
•Presence of active UC spread beyond the rectum (inflammation extending = 15cm from anal verge) as evidenced by flexible sigmoidoscopy or colonoscopy during the screening window.
•AND MAYO score of 5 – 10 inclusive.
6. AST and ALT < 2xULN; alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion criteria:
A subsject will not be eligible in this study if any of the following citeria apply:
1. If female, is pregnant, has a positive pregnancy test or is breast-feeding.
2. Confirmed diagnosis of celiac disease, those who follow a gluten-free diet to manage symptoms of suspected celiac disease and subjects with positive serologic test for Tissue Transamininase, tTG.
3. Subjects who have received immunisation with a live vaccine e.g. measles, mumps, rubella (each as MMR vaccine), oral polio, varicella, yellow fever, within 4 weeks of screening throughout the study, with the exception of influenza vaccine.
4. Known or suspicion of CD, indeterminate colitis, microscopic colitis, ischaemic colitis or radiation-induced colitis, based on medical history, endoscopy and/or histological findings.
5. Subjects with imminent need for surgery for UC in the opinion of the investigator.
6. Subjects where assessment of MAYO score is likely to be confounded by previous surgery (for example colectomy, ileostomies, colostomies or rectal pouches).
7. Subjects requiring enteral or parenteral feeding.
8. Use of prohibited medications within their specified timeframes (see Section 9).
•5-Aminosalicylic acid enema: within 2 weeks of screening and throughout study
•Topical (suppository) 5-Aminosalicylic acid: at screening and throughout study
•Biologic use: within 12 weeks of screening and throughout study
•Corticosteroids use: Oral, rectal or parenteral corticosteroids within 4 weeks of screening and throughout study
•Antibiotics: Intravenous antibiotics within 8 weeks of screening and throughout study (oral antibiotics are permitted where they have been used for >4 weeks with stable dose for =2 weeks prior to screening)
•Probiotics: within 4 weeks of screening (patients who initiated probiotics or prebiotics more than 4 weeks prior to screening should continue use throughout study)
•NSAIDs: Within 7 days of screening and throughout the study (except low dose aspirin (=325 mg/day) which may be continued for cardioprotection)
•Digoxin: or related cardiac glycoside (e.g. digitoxin, deslanoside, lanatoside C, metildigoxin) use at any time during screening and throughout the study.
9. Known HIV infection
10. A positive HBsAg, Anti-HBc, or Hepatitis C antibody result at screening or documented positive result within 3 months of screening.
11. Known varicella, herpes zoster, or other severe viral infection within 6 weeks of screening.
12. Active or latent tuberculosis (TB) infection:
•The subject has a history of TB disease or latent TB infection, in the absence of documented adequate therapy for same.
•Suspicion of current TB disease (including extra pulmonary TB disease such as tuberculosis enteritis) or latent tuberculosis infection, as evidenced by positive QuantiFERON-TB Gold test, or T-SPOT.TB test.
13. Current or chronic history of liver disease or known hepatic or biliary abnormalities including primary sclerosing cholangitis (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
14. QTc =450 msec (=480msec for those with Bundle Branch Block).
•either QTcb or QTcf, machine or manual overread, males or females. The QT correction formula used to determine exclusion and discontinuation should be the same throughout the study.
•based on single QTc value of ECG obtained over a brief recording period.
15. The subject has a concurrent illness or disability that may affect the interpretation of clinical data, or otherwise contr

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

Health Condition(s) or Problem(s) studied

Subjects with Active Ulcerative Colitis.
MedDRA version: 14.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis 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
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)

Timepoint(s) of evaluation of this end point: MAYO score assessment during the screening (from – 30 days to -1 day before the start of the treatment phase) and at week 12 during the treatment phase.

Main Objective: -To investigate the efficacy of GSK1605786 at week 12 following twice daily administration at 500 mg in patients with active Ulcerative Colitis (UC).

Primary end point(s): •Ordinal response (remission, response, or no response) to treatment as assessed by the MAYO score at week 12.

Secondary Objective: -To explore safety, tolerability and the time course of the efficacy of GSK1605786 following repeat dosing continued for up to 16 weeks.
-To assess the anti-inflammatory activity of GSK1605786 on blood and faecal biomarkers of intestinal inflammation.
-To investigate the systemic pharmacokinetics of GSK1605786 following twice daily administration at 500 mg.
-To measure CCR9 occupancy (RO) in peripheral blood following twice daily administration at 500 mg of GSK1605786 and to determine TECK/CCL25 and CCR9 expression in colonic mucosa.
-To assess the effect of GSK1605786 on leukocyte migration to the inflamed large intestine and to thymus.
-To explore changes in circulating immune cells following treatment for up to 16 weeks with GSK1605786.
-To explore changes in immune cells present in mucosal biopsies and changes in gene and protein expression in blood and in mucosal biopsies from large bowel following treatment for up to 12 weeks with GSK1605786.

Secondary Outcome(s)

Secondary end point(s): •Safety and tolerability as determined by:
1 - Adverse events (AEs);
2 - Treatment effects on blood pressure, heart rate, electrocardiography (ECG) parameters and haematology, clinical chemistry and urinalysis findings.
• Incidence of remission (MAYO score = 2 with no individual subscale exceeding 1).
• Incidence of response (MAYO score decreased for = 3 points in comparison with baseline).
• Incidence of endoscopic remission (mucosal healing) rate at Week 12, defined as proportion of patients with endoscopy score of 0 or 1 on the MAYO endoscopic subscale.

Timepoint(s) of evaluation of this end point: • Adverse events (AEs); Treatment effects on blood pressure, heart rate, electrocardiography (ECG) parameters and haematology, clinical chemistry and urinalysis findings up to and including week 20.
• Incidence of remission (MAYO score = 2 with no individual subscale exceeding 1) at Week 12.
• Incidence of response (MAYO score decreased for = 3 points in comparison with baseline) at Week 12.
• Incidence of endoscopic remission (mucosal healing) rate at Week 12.

Secondary ID(s)

CCX115393

Source(s) of Monetary Support

GSK R & D Ltd