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

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official 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 Wi

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

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome: Efficacy of GSK1605786 at week 12 following twice daily administration at 500 mg in patients with active UC. [ Time Frame: 12 weeks ]

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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • safety and tolerability of GSK1605786 in patients with active UC following repeat dosing continued for up to 16 weeks [ Time Frame: 16 weeks ]
    Adverse events (AEs), Treatment effects on blood pressure, heart rate, electrocardiography (ECG) parameters and haematology, clinical chemistry and urinalysis findings
  • The time course of the efficacy of GSK1605786 [ Time Frame: 16 Weeks ]
    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, change in partial MAYO score compared to baseline through week 16, change in SCCAI score compared to baseline through week 16, 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 sub-scale) and time to withdrawal and/or use of rescue medication
  • The anti-inflammatory activity of GSK1605786 in patients with active UC [ Time Frame: 16 Weeks ]
    Circulating soluble biomarkers (CRP, CXL10), faecal calprotectin levels, receptor occupancy (CCR9 internalization).
  • The effects of GSK1605786 on quality of life in patients with UC [ Time Frame: Baseline, week 12, week 16 ]
    Quality of Life (IBDQ) Questionnaire.
  • The systemic pharmacokinetics (PK) of GSK1605786 following twice daily administration at 500 mg in patients with active UC. [ Time Frame: DaysBaseline, week 4, week 8, week 12, week 16 ]
    The maximum observed concentration (Cmax) on Day 28; Trough concentration (Cτ) on Day 28; Plasma clearance and volume of distribution estimated based on population pharmacokinetic analysis of healthy volunteers (historical data) and patient data, if possible
  • CCR9 occupancy (RO) in peripheral blood [ Time Frame: 12 Weeks ]
    TECK/CCL25 and CCR9 expression in colon biopsy at baseline and at 12 weeks


Original Secondary Outcome: Same as current

Information By: GlaxoSmithKline

Dates:
Date Received: May 24, 2012
Date Started: February 2013
Date Completion: December 2014
Last Updated: June 20, 2013
Last Verified: June 2013