Open-Label Extension Study of GSK1605786A (SHIELD-3)

GlaxoSmithKline (GSK)

Status and phase

Terminated

Phase 3

Conditions

Crohn's Disease

Treatments

Drug: GSK1605786A

Study type

Interventional

Funder types

Industry

Identifiers

NCT01318993

2010-022384-35 (EudraCT Number)

114644

Details and patient eligibility

About

An open-label study to evaluate the safety and effectiveness of GSK1605786A 500 mg twice daily over 108 weeks in adult subjects with Crohn's disease. Subjects completing previous GSK-sponsored studies with GSK1605786A or subjects who withdraw early from Study CCX114157 (maintenance study of GSK1605786A) due to worsening of Crohn's disease requiring a treatment change may be eligible to participate. The primary objective is to evaluate the safety of GSK1605786A, as assessed by recording of adverse events, clinical laboratory parameters, vital signs and electrocardiogram. Secondary objectives will include assessments of effectiveness of long-term treatment with GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire (IBDQ), SF-36v2, EQ-5D, Work and Productivity Activity Impairment-Crohn's Disease (WPAI-CD) and receipt of disability.

Full description

This is a multi-centre, open-label extension study to assess the long-term safety, tolerability and effectiveness of GSK1605786A in subjects with Crohn's disease. Subjects will enter the study via one of three routes:

completion of the placebo-controlled induction study, CCX114151, without achieving clinical response (CDAI decrease of at least 100 points) or clinical remission (CDAI score less than 150) at Week 12 or completion of any other GSK-sponsored induction study as designated by the sponsor
completion of maintenance study CCX114157 at Week 52
withdrawal from maintenance study CCX114157 due to worsening of Crohn's disease and requiring a treatment change.

The primary objective is to evaluate the safety of GSK1605786A, as assessed by recording of adverse events, clinical laboratory parameters, vital signs and electrocardiogram. Secondary objectives will include assessments of effectiveness of long-term treatment with GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire (IBDQ), SF-36v2, EQ-5D, Work and Productivity Activity Impairment-Crohn's Disease (WPAI-CD) and disability.

It is estimated that approximately 800 subjects will be enrolled in total. All subjects will enter the study at baseline (Week 0) and commence oral treatment with GSK1605786A 500 mg twice daily.

The study will be conducted for 108 weeks. Once the results of the induction study CCX114151 are known, the risk-to-benefit ratio will be re-assessed and the study duration may be amended.

Study assessments for Crohn's disease will be performed every 12 weeks through Week 108. At week 12, the investigator will make a determination of whether the subject is receiving clinical benefit, and subjects who are not receiving clinical benefit must be withdrawn. More frequent blood draws are required for liver function testing only; every 2 weeks for the first 12 weeks, then every 4 weeks up to Week 52, and every 12 weeks after Week 60 for the duration of the study.

Enrollment

399 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Previous participation in a GSK-sponsored study with GSK1605786A
Written informed consent prior to any study-specific procedures
Female subjects: To be eligible, females of child-bearing potential must be sexually inactive or commit to consistent and correct use of a contraceptive method of birth control with less than 1% failure rate

Exclusion criteria

If female, is pregnant, has a positive pregnancy test or is breast-feeding, or is planning to become pregnant
Subjects with known or suspected coeliac disease or a positive screening test for anti-tissue transglutaminase antibodies should have been excluded from enrolment into any induction study. Subjects in whom a diagnosis of coeliac disease is subsequently suspected should be tested for anti-tissue transglutaminase antibodies and excluded or withdrawn from the study upon positive test result
Fixed symptomatic stenoses or strictures of small bowel or colon
Enterocutaneous, abdominal or pelvic fistulae likely to require surgery during the study period
Current sepsis or infections requiring intravenous antibiotic therapy greater than 2 weeks
Evidence of hepatic dysfunction or viral hepatitis
Subjects who have demonstrated safety or tolerability issues during participation in a previous study with GSK1605786A which, in the opinion of the investigator, was possibly related to study treatment and poses an unacceptable risk to the subject.