Phase 4 Study to Evaluate the Efficacy and Safety of Vedolizumab in the Treatment of Chronic Pouchitis (EARNEST)
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|ClinicalTrials.gov Identifier: NCT02790138|
Recruitment Status : Recruiting
First Posted : June 3, 2016
Last Update Posted : April 23, 2018
|Condition or disease||Intervention/treatment||Phase|
|Colitis, Ulcerative||Drug: Vedolizumab Drug: Ciprofloxacin Drug: Vedolizumab Placebo||Phase 4|
Vedolizumab is being tested to treat people who have chronic pouchitis. This study will look at the healing of inflammation of ileal pouch in people who take vedolizumab as compared to those receiving a matching placebo. The study will enroll approximately 110 patients. Participants will be randomly assigned to one of the two treatment groups—which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):
- Vedolizumab 300 mg IV
All participants will receive an intravenous infusion at Weeks 0, 2, 6, 14, 22, and 30 along with concomitant antibiotic treatment with ciprofloxacin 500 mg twice daily through Week 4.
This multicenter trial will be conducted in North America and Europe. The overall time to participate in treatment and efficacy assessment of this study is 34 weeks. Participants will make multiple visits to the clinic, plus a final visit 18 weeks after the last dose of study drug for a safety follow-up assessment (up to Week 48). Participants will also participate in a long-term follow-up, by phone after the last dose of study drug up to Week 56.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||110 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double-Blind, Placebo-Controlled Phase 4 Study to Evaluate the Efficacy and Safety of Entyvio (Vedolizumab IV) in the Treatment of Chronic Pouchitis (EARNEST)|
|Actual Study Start Date :||October 12, 2016|
|Estimated Primary Completion Date :||March 9, 2019|
|Estimated Study Completion Date :||March 9, 2019|
Experimental: Vedolizumab 300 mg
Vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2, 6, 14, 22, and 30 along with ciprofloxacin 500 mg, tablet, orally twice daily up to Week 4.
Vedolizumab IV infusion
Other Names:Drug: Ciprofloxacin
Placebo Comparator: Placebo
Vedolizumab placebo-matching IV infusion, once at Weeks 0, 2, 6, 14, 22, and 30 along with ciprofloxacin 500 mg, tablet, orally twice daily up to Week 4.
Ciprofloxacin TabletsDrug: Vedolizumab Placebo
Vedolizumab placebo-matching IV infusion
- Percentage of Participants with Chronic or Recurrent Pouchitis Achieving Clinically Relevant Remission after 14 Weeks of Treatment [ Time Frame: Week 14 ]Clinically relevant remission is defined as a modified pouchitis disease activity index (mPDAI) score <5 and a reduction of overall score by ≥2 points from Baseline. The mPDAI scale was developed as an objective, and quantitative criteria for pouch inflammation after ileal pouch anal anastomosis (IPAA). The 12-point overall score is calculated from 2 separate 6-point scales based on clinical symptoms (0 to 6), endoscopic findings (0 to 6). A cutoff of 5 differentiates participants with pouchitis (mPDAI ≥5) from participants without pouchitis (mPDAI <5).
- Percentage of Participants Achieving mPDAI Score <5 and a Reduction of Overall Score by ≥2 Points From Baseline after 34 Weeks of Treatment [ Time Frame: Week 34 ]
- Percentage of Participants Achieving PDAI score <7 and a Reduction of Overall Score by ≥3 Points from Baseline PDAI Score after 14 Weeks of Treatment and after 34 Weeks of Treatment [ Time Frame: Weeks 14 and 34 ]PDAI is an objective and quantitative criteria for pouch inflammation after IPAA. The 18-point overall score is calculated from 3 separate 6-point scales based on clinical symptoms (0 to 6), endoscopic findings (0 to 6) and histologic changes (0 to 6). The PDAI incorporates histologic features of acute inflammation, along with symptom and inflammation on endoscopy, and establishes a cut-off of 7 for differentiation between 'pouchitis' (≥7 points) and 'no pouchitis' (<7 points).
- Time to Remission [ Time Frame: Baseline up to Week 34 ]Remission is defined as a PDAI score <7 and a decrease in PDAI score of ≥3 points from Baseline.
- Percentage of Participants Achieving a Partial Response after 14 and 34 Weeks of Treatment [ Time Frame: Weeks 14 and 34 ]Partial response is defined as a reduction in mPDAI score by ≥2 points from Baseline.
- Change in PDAI Endoscopic Subscore at Weeks 14 and 34 Compared to Baseline [ Time Frame: Baseline, Weeks 14 and 34 ]PDAI endoscopic subscore includes edema, granularity, friability, loss of vascular pattern, mucous exudates and ulcerations. Each item is scored on a scale of 0 to 1. A PDAI endoscopic subscore is calculated by summing the scores from each endoscopic finding. Total score ranges from 0 to 6. Maximum score indicates greater severity of the disease.
- Change in PDAI Histologic Subscore at Weeks 14 and 34 Compared to Baseline [ Time Frame: Baseline, Weeks 14 and 34 ]PDAI histologic subscore includes polymorphic nuclear leukocyte infiltration (mild=1; moderate + crypt abscess=2 and severe + crypt abscess=3) and ulceration per low power field (mean). A PDAI histologic subscore is calculated by summing the scores from each finding. Total score ranges from 0 to 6. Maximum score indicates greater severity of the disease.
- Change in Total PDAI Score at Weeks 14 and 34 Compared to Baseline [ Time Frame: Baseline, Weeks 14 and 34 ]
- Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 14, 22 and 34 Compared to Baseline [ Time Frame: Baseline, Weeks 14, 22 and 34 ]The IBDQ is an instrument used to assess quality of life in adult participants with inflammatory bowel disease (IBD). It includes 32 questions on 4 domains of Health-Related Quality-of-Life (HRQOL): Bowel Systems (10 items), Emotional Function (12 items), Social Function (5 items), and Systemic Function (5 items). Participants are asked to recall symptoms and quality of life from the last 2 weeks and rate each item on a 7-point Likert scale (1=worst to 7=best). A total IBDQ score is calculated by summing the scores from each domain; the total IBDQ score ranges from 32 to 224, with lower scores reflecting worse HRQOL.
- Change in Cleveland Global Quality of Life (CGQL) at Weeks 14, 22 and 34 Compared to Baseline [ Time Frame: Baseline, Weeks 14, 22 and 34 ]The CGQL (Fazio score) is a quality-of-life indicator specifically for participants with ileal pouch-anal anastomosis. Participants rate 3 items (current quality of life, current quality of health, and current energy level), each on a scale of 0 to 10 (0=worst; 10=best). The scores are added, and the final CGQL utility score is obtained by dividing this result by 30.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02790138
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|Study Director:||Medical Director Clinical Science||Takeda|