GSK1605786A in the Maintenance of Remission in Subjects With Crohn's Disease (SHIELD-2)

GlaxoSmithKline (GSK)

Status and phase: Terminated; Phase 3

Conditions: Crohn's Disease

Treatments: Drug: GSK1605786A; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01316939

2010-022383-12 (EudraCT Number)

114157

Details and patient eligibility

About

A randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of two doses (500 mg once daily and 500 mg twice daily) of GSK1605786A in maintaining remission over 52 weeks in adult subjects with Crohn's disease. Efficacy will be assessed by the Crohn's Disease Activity Index (CDAI) score. Eligible subjects will have achieved response (CDAI decrease of at least 100 points) and/or remission (CDAI less than 150) in a prior GSK sponsored induction study. The primary endpoint will be proportion of subjects in remission at both Weeks 28 and 52. Safety will be assessed by recording of adverse events, clinical laboratory parameters including liver function tests, vital signs and electrocardiogram. Population pharmacokinetics will evaluate the two doses of GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire (IBDQ), SF-36v2, EQ-5D, Work Productivity and Activity Impairment - Crohn's Disease (WPAI-CD) and disability.

Full description

This is a multi-centre, randomised, placebo-controlled, double-blind parallel group study in adult subjects with Crohn's disease who previously achieved clinical response (CDAI decrease of at least 100 points) and/or remission (CDAI less than 150) in a prior Phase III induction study (Study CCX114151 or another GSK sponsored induction study). Subjects will be randomised to 52 weeks of oral treatment with GSK1605786A 500 mg once daily or 500 mg twice daily or placebo. Subjects who are receiving concomitant corticosteroids at entry will undergo dose tapering following a defined schedule. Subjects who complete the treatment period may be eligible to enter an open-label extension study. Subjects who experience disease worsening and require additional (rescue) treatment will be withdrawn and may be eligible to enter the open-label study. Subjects who do not enter the open-label study must complete a follow-up assessment 4 weeks after completion of treatment. Approximately 756 subjects will be enrolled.

Enrollment: 229 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects achieving clinical response (CDAI decrease of at least 100 points) and/or remission (CDAI less than 150) upon completion of treatment in Study CCX114151 or another GSK sponsored induction study
• Written informed consent prior to any CCX114157 specific study procedures
• Females of child-bearing potential must be sexually inactive or commit to use of consistent and correct use of contraceptive methods with a failure rate of less than 1 percent
• Stable doses of Crohn's disease medications
• Subjects on corticosteroids at entry must be willing to undergo corticosteroid dose taper during the study

Exclusion criteria

• If female, is pregnant, has a positive pregnancy test or is breast-feeding
• Subjects with known or suspected coeliac disease or a positive screening test (anti-tissue transglutaminase antibodies) should have been excluded from enrolment into the induction studies. Subjects in whom a diagnosis of coeliac disease is subsequently suspected should have this excluded with testing for anti-tissue transglutaminase antibodies prior to enrolment into the maintenance study.
• Known or suspected fixed symptomatic small bowel stricture
• Enterocutaneous, abdominal or pelvic fistulae likely to require surgery during the study period
• Current sepsis or infections requiring intravenous antibiotic therapy for greater than 2 weeks
• Evidence of hepatic dysfunction, viral hepatitis, or liver function abnormalities

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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229 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo

GSK1605786A once daily

Experimental group

Description:

500 milligrams once daily

Treatment:

Drug: GSK1605786A

Drug: GSK1605786A

GSK1605786A twice daily

Experimental group

Description:

500 milligrams twice daily

Treatment:

Drug: GSK1605786A

Drug: GSK1605786A