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)
Overview
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Takeda
- Enrollment
- 102
- Locations
- 34
- Primary Endpoint
- Percentage of Participants With Chronic or Recurrent Pouchitis Achieving Clinically Relevant Remission at Week 14
Overview
Brief Summary
The purpose of this study is to compare the efficacy of vedolizumab intravenous (IV) and placebo in terms of the percentage of participants with chronic or recurrent pouchitis achieving clinically relevant remission.
Detailed Description
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
- Placebo IV
All participants will receive an intravenous infusion at Day 1, Weeks 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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
- •The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
- •Has a history of ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) completed at least 1 year prior to the Day 1 (Randomization) Visit.
- •Has pouchitis that is chronic or recurrent, defined by an modified pouchitis disease activity index (mPDAI) score ≥5 assessed as average from 3 days immediately prior to the Baseline endoscopy and a minimum endoscopic subscore of 2 (outside the staple or suture line) with either (a) ≥3 recurrent episodes within 1 year prior to the Screening Period treated with ≥2 weeks of antibiotic or other prescription therapy, or (b) requiring maintenance antibiotic therapy taken continuously for ≥4 weeks immediately prior to the Baseline Endoscopy Visit.
- •Agrees to take ciprofloxacin (500 mg twice daily) on Day 1 and through Week 4, regardless of the previous treatment and to stop any previous antibiotic therapy on Day 1 of the study (additional courses of antibiotics will be allowed, as needed, for flares after Week 14).
- •A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use a barrier method of contraception (e.g., condom with spermicide) from signing of informed consent throughout the duration of the study and for 18 weeks after last dose. The female partner of a male participant should also be advised to use a highly effective method of contraception.
- •A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use a highly effective method of contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
Exclusion Criteria
- •Gastrointestinal Exclusion Criteria
- •Has Crohn's disease (CD), or CD of the pouch.
- •Has irritable pouch syndrome (IPS).
- •Has isolated or predominant cuffitis.
- •Has mechanical complications of the pouch (e.g., pouch stricture or pouch fistula).
- •Currently requires or has a planned surgical intervention for UC during the study.
- •Has diverting stoma.
- •Infectious Disease Exclusion Criteria
- •Has evidence of an active infection (e.g., sepsis, cytomegalovirus, or listeriosis) during Screening.
- •Has active or latent tuberculosis (TB), regardless of treatment history, as evidenced by any of the following:
Arms & Interventions
Placebo IV
Vedolizumab placebo-matching intravenous (IV) infusion, once at Day 1, Weeks 2, 6, 14, 22, and 30 along with ciprofloxacin 500 mg, tablet, orally twice daily up to Week 4.
Intervention: Vedolizumab Placebo (Drug)
Placebo IV
Vedolizumab placebo-matching intravenous (IV) infusion, once at Day 1, Weeks 2, 6, 14, 22, and 30 along with ciprofloxacin 500 mg, tablet, orally twice daily up to Week 4.
Intervention: Ciprofloxacin (Drug)
Vedolizumab IV 300 mg
Vedolizumab 300 mg, IV infusion, once at Day 1, Weeks 2, 6, 14, 22, and 30 along with ciprofloxacin 500 mg, tablet, orally twice daily up to Week 4.
Intervention: Vedolizumab (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With Chronic or Recurrent Pouchitis Achieving Clinically Relevant Remission at Week 14
Time Frame: Week 14
Clinically relevant remission is defined as modified Pouchitis Disease Activity Index (mPDAI) score \<5 and a reduction of mPDAI score by ≥2 points from Baseline. The 12-point mPDAI score is calculated as a sum of from two 6-point subscales, where 0 = best and 12 = worst.: 1) Clinical Symptoms: Stool Frequency (0=usual to postoperative stool frequency to 2=three or more stools/day\>postoperative usual); Rectal bleeding (0=None or rare to 1=Present daily); Fecal urgency or abdominal cramps (0=None to 2=Usual), Fever \[temperature \>37.8 degrees C\] (0=Absent and 1=Present) for a clinical symptoms subscore of 0 (best) to 6 (worse); 2) Endoscopic Inflammation Findings: Edema, Granularity, Friability, Loss of vascular pattern, Mucous exudates and Ulcerations. Each item is scored on a scale of 0=not present to 1=present summed up to an endoscopic subscore ranging from 0 (best) to 6 (worst) where higher scores indicate more severe disease.
Secondary Outcomes
- Percentage of Participants With Chronic or Recurrent Pouchitis Achieving Clinically Relevant Remission at Week 34(Week 34)
- Percentage of Participants Achieving Pouchitis Disease Activity Index (PDAI) Remission at Weeks 14 and 34(Weeks 14 and 34)
- Time to PDAI Remission(Baseline up to Week 34)
- Percentage of Participants Achieving a Partial mPDAI Response at Weeks 14 and 34(Weeks 14 and 34)
- Change From Baseline in PDAI Endoscopic Inflammation Subscore at Weeks 14 and 34(Baseline up to Weeks 14 and 34)
- Change From Baseline in PDAI Acute Histologic Inflammation Subscore at Weeks 14 and 34(Baseline up to Weeks 14 and 34)
- Change From Baseline in Total PDAI Score at Weeks 14 and 34(Baseline up to Weeks 14 and 34)
- Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 14, 22, and 34(Baseline up to Weeks 14, 22, and 34)
- Change From Baseline in Cleveland Global Quality of Life (CGQL) at Weeks 14, 22, and 34(Baseline up to Weeks 14, 22, and 34)