Efficacy and Safety of Filgotinib in Active Crohn's Disease
Research type
Research Study
Full title
Combined Phase 3, Double-blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Fligotinib in the Induction and Maintenance of Remission in Subjects with Moderately to Severely Active Crohn's Disease
IRAS ID
209259
Contact name
Ian Beales
Contact email
Sponsor organisation
Gilead Sciences Inc.
Eudract number
2016-001367-36
Clinicaltrials.gov Identifier
129646, IND Number
Duration of Study in the UK
2 years, 10 months, 31 days
Research summary
Research Summary:
This is a randomised, double-blind, placebo-controlled study investigating the treatment of Crohn’s disease (CD). CD is an inflammatory bowel disease of the gastrointestinal tract (digestive tract) that causes sufferers to have symptoms of diarrhoea, abdominal pain, weight loss and the passage of blood through the rectum. In the United States and Europe it is suggested that up to 1.5 million individuals may be affected. CD is a chronic condition which means that it is ongoing and life-long, although suffers might have periods of good health (remission), as well as times when symptoms are more active (relapses). There is no a cure for CD, but there are treatments that can help to settle relapses and keep symptoms away for longer. The purpose of this study is to see if filgotinib (the study medication) is effective and safe in treating people with moderate to severe Crohn’s disease (CD)
In this study, approximately 1320 male and female patients will be enrolled, aged 18 to 75, at around 400 centres worldwide.
During the first part (induction), participants will be randomly assigned to one of following treatment groups:
• Treatment 1: filgotinib 200 mg daily
• Treatment 2: filgotinib 100 mg daily
• Treatment 3: placebo dailyAfter 10 weeks, depending on the treatment group assigned during part one (induction), participants will then be assigned to another treatment group for the second part of the study (maintenance).
Eligible participants will visit the clinic at least 13 times (19 times if the participant is a woman who can get pregnant) over 58 weeks. They will undergo various study procedures to assess the safety and effectiveness of filgotinib. Depending on their treatment response at or after week 10, there may be an option to then enrol in a Long Term Extension study.
Summary of Results:
GS-US-419-3895 (GLPG0634-CL-309, DIVERSITY 1) is a combined Phase 3 double-blind, randomised, placebo-controlled study evaluating the efficacy and safety of 2 doses of filgotinib (100 mg and 200 mg) for the induction and maintenance of remission in adult subjects with moderately to severely active Crohn’s Disease (CD). The study comprises two 11-week induction studies (Cohort A Induction Study and Cohort B Induction Study), followed by a 47-week Maintenance Study.
None of the induction studies met both co-primary endpoints (the events or outcomes that can be measured objectively to determine whether the intervention being studied is beneficial). In the Cohort A Induction Study, none of the EU-specific co-primary endpoints (patient-reported outcome (PRO2) remission and endoscopic response) were met at Week 10 as a statistically significant result was not seen for either 100 mg nor 200 mg filgotinib. In the non-EU analysis, one of the co-primary endpoints (Crohn’s Disease Activity Index (CDAI) remission) was met with filgotinib at 200 mg.
In the Cohort B Induction Study, one of the co-primary endpoints was met at Week 10 with filgotinib 200 mg (PRO2 remission in the EU-specific analysis and CDAI remission in the non-EU analysis). Filgotinib 100 mg did not meet any of the co-primary endpoints in the induction studies.
In the Maintenance Study, both EU-specific co-primary endpoints were met for filgotinib 200 mg; there was a statistically significant difference for filgotinib 200 mg compared with placebo in the proportion of subjects achieving clinical remission by PRO2 and endoscopic response at Week 58. With respect to the non-EU co-primary endpoints, one of the co-primary endpoints (endoscopic response) was met at Week 58 with filgotinib200 mg, but the other co-primary endpoint (clinical remission by CDAI) was not met. Filgotinib 100 mg did not meet any of the EU-specific or non-EU co-primary endpoints in the Maintenance Study. The overall safety profile was consistent with that observed for filgotinib in the approved indications of rheumatoid arthritis and ulcerative colitis.
REC name
South Central - Hampshire B Research Ethics Committee
REC reference
16/SC/0630
Date of REC Opinion
4 Jan 2017
REC opinion
Further Information Favourable Opinion