A Study to Evaluate the Efficacy and Safety of Vedolizumab in the Treatment of Chronic Pouchitis

NCT ID: NCT02790138

Last Updated: 2022-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-12
• Study Completion Date: 2021-02-02

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.

Conditions

Pouchitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Vedolizumab Placebo

Intervention Type: DRUG

Vedolizumab placebo-matching IV infusion

Ciprofloxacin

Intervention Type: DRUG

Ciprofloxacin tablets

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.

Group Type: EXPERIMENTAL

Vedolizumab

Intervention Type: DRUG

Vedolizumab IV infusion

Interventions

Vedolizumab Placebo

Vedolizumab placebo-matching IV infusion

Intervention Type: DRUG

Ciprofloxacin

Ciprofloxacin tablets

Intervention Type: DRUG

Vedolizumab

Vedolizumab IV infusion

Intervention Type: DRUG

Other Intervention Names

Entyvio; MLN0002 IV; Kynteles

Eligibility Criteria

Inclusion Criteria

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

2. 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.

3. 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.

4. 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.

5. 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).

6. 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.

7. 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

1. Has Crohn's disease (CD), or CD of the pouch.

2. Has irritable pouch syndrome (IPS).

3. Has isolated or predominant cuffitis.

4. Has mechanical complications of the pouch (e.g., pouch stricture or pouch fistula).

5. Currently requires or has a planned surgical intervention for UC during the study.

6. Has diverting stoma.

2. Has active or latent tuberculosis (TB), regardless of treatment history, as evidenced by any of the following:

1. A diagnostic TB test performed within 30 days of Screening or during the Screening Period that is positive, as defined by:

1. A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests. OR

2. A tuberculin skin test reaction ≥10 mm (≥5 mm in participants receiving the equivalent of >15 mg/day prednisone).

OR

2. Chest X-ray within 3 months prior to Day 1 that is suspicious for pulmonary TB, and a positive or 2 successive indeterminate QuantiFERON test within 30 days prior to Screening or during the Screening Period.

3. Has chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV) infection** or a known history of human immunodeficiency virus (HIV) infection (or is found to be seropositive at Screening) or participant is immunodeficient (e.g., due to organ transplantation, history of common variable immunodeficiency, etc).

• Participants who are positive for hepatitis B virus surface antigen (HBsAg) will be excluded. For participants who are negative for HBsAg but are positive for either surface antibodies and/or core antibodies, HBV Deoxyribonucleic acid (DNA) polymerase chain reaction will be performed and if any test result meets or exceeds detection sensitivity, the participant will be excluded.
• If participant is HCV antibody positive, then a viral load test will be performed. If the viral load test is positive then the participant will be excluded.

4. Has evidence of active infection with Clostridium (C) difficile during Screening (to be confirmed by laboratory test)

1. Has any prior exposure to vedolizumab, natalizumab, efalizumab, rituximab, etrolizumab, or anti-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) therapy.

2. Has a history of hypersensitivity or allergies to vedolizumab or its components.

3. Has allergies to and/or contraindications for ciprofloxacin, a history of tendon disorders related to quinolone administration and/or glucose-6-phosphate dehydrogenase (G6PD) deficiency. Further conditions requiring precautions for use of ciprofloxacin have to be considered based on local prescribing information.

4. Is taking, has taken, or is required to take any excluded medications.

5. Has received any investigational or approved biologic or biosimilar agent within 60 days prior to Randomization.

6. Has received an investigational nonbiologic therapy within 30 days prior to Randomization.

7. Has received an approved nonbiologic therapy (including 5-aminosalicylate [5-ASA], corticosteroid, azathioprine, 6-mercaptopurine [6-MP], etc.) in an investigational protocol within 30 days prior to Randomization.

8. Has received any live vaccinations within 30 days prior to randomization.

9. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist at Screening.

10. Has had a kidney, heart, or lung transplant.

11. Has a history of malignancy, except for the following: adequately-treated non-metastatic basal cell skin cancer; squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to the Screening visit; and history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to Screening. Participants with a remote history of malignancy (e.g., >10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received and must be discussed with the sponsor on a case-by-case basis prior to enrollment.

12. Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating, or neurodegenerative disease.

13. Has conditions, which in the opinion of the investigator, may interfere with the participant's ability to comply with the study procedures.

14. Has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal (GI), genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurologic, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise participant safety.

15. Has any of the following laboratory abnormalities during the Screening Period:

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1. Hemoglobin level <8 g/dL.

2. White blood cell (WBC) count <3 × 10^9/L.

3. Lymphocyte count <0.5 × 10^9/L.

4. Platelet count <100 × 10^9/L or >1200 × 10^9/L.

5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × the upper limit of normal (ULN).

6. Alkaline phosphatase >3 × ULN.

7. Serum creatinine >2 × ULN.

16. If female, the participant is pregnant or lactating or intending to become pregnant or nurse before, during, or within 18 weeks after the last dose of study medication; or intending to donate ova during such time period.

17. If male, the participant intends to donate sperm or father a child during the course of this study or for 18 weeks after the last dose of study medication.

18. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.

19. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to Screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

University of Chicago Medical Center

Chicago, Illinois, United States

Northshore University HealthSystem

Evanston, Illinois, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

University of North Carolina GI

Chapel Hill, North Carolina, United States

Carolinas HealthCare System Digestive Health

Charlotte, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Texas Digestive Disease Consultants

Southlake, Texas, United States

University of Utah Health Sciences Center

Salt Lake City, Utah, United States

UZ Leuven - University Hospital Gasthuisberg

Leuven, , Belgium

GIRI (GI Research Institute)

Vancouver, British Columbia, Canada

Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

CHU de Rennes - Hopital de Pontchaillou

Rennes, , France

CHU Saint Etienne - Hopital Nord

Saint-Priest-en-Jarez, , France

CHU de Toulouse - Hopital Rangueil

Toulouse, , France

CHRU Nancy Hopital de Brabois

Vandœuvre-lès-Nancy, , France

Charite Universitatsmedizin Berlin -Campus Virchow Klinikum

Berlin, , Germany

Asklepios Hospital Hamburg - West

Hamburg, , Germany

Praxis fuer Gastroenterologie, Drs. Ehehalt/ Helmstaedter

Heidelberg, , Germany

Universitatsklinikum Jena

Jena, , Germany

Klinikum Mannheim GmbH Universitaetsklinikum

Mannheim, , Germany

Azienda Ospedaliera S. Orsola-Malpighi

Bologna, , Italy

Azienda Ospedaliera di Padova

Padua, , Italy

Policlinico Gemelli

Rome, , Italy

Istituto Clinico Humanitas IRCCS

Rozzano, , Italy

Academic Medical Center

Amsterdam, , Netherlands

Maastricht University Medical Center

Maastricht, , Netherlands

Hospital Doctor Negrin

Las Palmas de Gran Canaria, , Spain

Hospital Universitario y Politecnico La Fe

Valencia, , Spain

St. Mark's Hospital

Harrow, , United Kingdom

Royal London Hospital

London, , United Kingdom

John Radcliffe Hospital

Oxford, , United Kingdom

Countries

United States; Belgium; Canada; France; Germany; Italy; Netherlands; Spain; United Kingdom

References

Jairath V, Feagan BG, Silverberg MS, Danese S, Gionchetti P, Lowenberg M, Bressler B, Ferrante M, Hart A, Lindner D, Escher A, Jones S, Shen B, Travis S. Mucosal Healing With Vedolizumab in Patients With Chronic Pouchitis: EARNEST, a Randomized, Double-Blind, Placebo-Controlled Trial. Clin Gastroenterol Hepatol. 2025 Feb;23(2):321-330.e3. doi: 10.1016/j.cgh.2024.06.037. Epub 2024 Jul 16.

Reference Type: DERIVED

PMID: 39025255 (View on PubMed)

Travis S, Silverberg MS, Danese S, Gionchetti P, Lowenberg M, Jairath V, Feagan BG, Bressler B, Ferrante M, Hart A, Lindner D, Escher A, Jones S, Shen B; EARNEST Study Group. Vedolizumab for the Treatment of Chronic Pouchitis. N Engl J Med. 2023 Mar 30;388(13):1191-1200. doi: 10.1056/NEJMoa2208450.

Reference Type: DERIVED

PMID: 36988594 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1171-0918

Identifier Type: REGISTRY

Identifier Source: secondary_id

2015-003472-78

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Vedolizumab-4004

Identifier Type: -

Identifier Source: org_study_id