A Study to Investigate the Efficacy and Safety of GSK1605786 for Treatment of Patients With Active Ulcerative Colitis

NCT01658605 | Withdrawn Phase 2

• 1 other identifier: 115393
• Study Type: interventional
• Target: N/A
• Locations: 3 countries
• Sites: 5

Brief Summary

GSK1605786 is an oral antagonist specific for the chemokine receptor CCR9 in development for treatment of small bowel and colonic Crohn's disease (CD). The purpose of this Phase II proof of concept study is to investigate the efficacy and safety of GSK1605786 (500 mg twice daily) administered orally for 16 weeks for the treatment of patients with active ulcerative colitis (UC). A key secondary objective is to understand the mechanism by which GSK1605786 is acting and to this end samples will be collected to confirm the degree of inhibition of CCR9 on T lymphocytes in the blood of patients, and to explore the relationship between concentration of drug and changes in lymphocyte and antigen presenting cell populations in the peripheral circulation and in the colon. Patients recruited at specified investigational sites will be invited to participate in an optional sub-study to explore the effects of GSK1605786 on trafficking of technetium labelled T cells using Single Photon Emission Computerized Tomography (SPECT). Specifically, the technique will be used to follow trafficking to large intestine and thymus and findings linked to pharmacokinetics of GSK1605786, receptor occupancy and clinical efficacy outcomes

Conditions

Colitis, Ulcerative

Keywords

GSK1605786; ulcerative colitis; CCR9 antagonist; proof of concept

Outcome Measures

Primary Outcomes (1)

• Efficacy of GSK1605786 at week 12 following twice daily administration at 500 mg in patients with active UC.

  Ordinal response (remission, response, or no response) to treatment as assessed by the MAYO score at week 12.

  12 weeks

Secondary Outcomes (6)

• safety and tolerability of GSK1605786 in patients with active UC following repeat dosing continued for up to 16 weeks

  16 weeks

• The time course of the efficacy of GSK1605786

  16 Weeks

• The anti-inflammatory activity of GSK1605786 in patients with active UC

  16 Weeks

• The effects of GSK1605786 on quality of life in patients with UC

  Baseline, week 12, week 16

• The systemic pharmacokinetics (PK) of GSK1605786 following twice daily administration at 500 mg in patients with active UC.

  DaysBaseline, week 4, week 8, week 12, week 16

Study Arms (2)

GSK1605786

EXPERIMENTAL

Administered orally for 16 weeks in a 2:1 ratio

Other: Placebo

Placebo

PLACEBO COMPARATOR

Administered orally for 16 weeks in a 2:1 ratio

Drug: GSK1605786

Interventions

GSK1605786 DRUG

500 mg twice daily administered orally

Placebo

Placebo OTHER

500 mg twice daily administered orally

GSK1605786

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18 and over at the time of signing the informed consent.
• 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.
• 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.
• 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.
• 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.
• AST and ALT \< 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN

You may not qualify if:

• If female, is pregnant, has a positive pregnancy test or is breast-feeding.
• 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 transglutaminase, tTG.
• 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.
• Known or suspicion of CD, indeterminate colitis, microscopic colitis, ischaemic colitis or radiation-induced colitis, based on medical history, endoscopy and/or histological findings.
• Subjects with imminent need for surgery for UC in the opinion of the investigator.
• Subjects where assessment of MAYO score is likely to be confounded by previous surgery (for example colectomy, ileostomies, colostomies or rectal pouches).
• Subjects requiring enteral or parenteral feeding.
• Use of prohibited medications within their specified timeframes (see Section 9).
• 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)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (5)

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Amsterdam, 1105 AZ, Netherlands

Location

GSK Investigational Site

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

GSK Investigational Site

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

GSK Investigational Site

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2012
• First Posted: August 7, 2012
• Study Start: February 1, 2013
• Primary Completion: February 1, 2013
• Study Completion: December 1, 2014
• Last Updated: June 24, 2013

Record last verified: 2013-06

Locations

BE (1); NL (1); GB (3)