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

NCT02790138 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: Vedolizumab-4004U1111-1171-09182015-003472-78
• Study Type: interventional
• Target: 102
• Locations: 9 countries
• Sites: 34

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.

Conditions

Pouchitis

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Chronic or Recurrent Pouchitis Achieving Clinically Relevant Remission at 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.

  Week 14

Secondary Outcomes (9)

• 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

Study Arms (2)

Placebo IV

PLACEBO COMPARATOR

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.

Drug: Vedolizumab Placebo; Drug: Ciprofloxacin

Vedolizumab IV 300 mg

EXPERIMENTAL

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.

Drug: Vedolizumab

Interventions

Vedolizumab Placebo DRUG

Vedolizumab placebo-matching IV infusion

Placebo IV

Ciprofloxacin DRUG

Ciprofloxacin tablets

Placebo IV

Vedolizumab DRUG

Vedolizumab IV infusion

Also known as: Entyvio, MLN0002 IV, Kynteles

Vedolizumab IV 300 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• \. Has active or latent tuberculosis (TB), regardless of treatment history, as evidenced by any of the following:
• A diagnostic TB test performed within 30 days of Screening or during the Screening Period that is positive, as defined by:
• A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests. OR
• A tuberculin skin test reaction ≥10 mm (≥5 mm in participants receiving the equivalent of \>15 mg/day prednisone).
• 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.
• \. 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.
• \. Has evidence of active infection with Clostridium (C) difficile during Screening (to be confirmed by laboratory test)

Sponsors & Collaborators

• Takeda: lead

Study Sites (34)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Northshore University HealthSystem

Evanston, Illinois, 60201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of North Carolina GI

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas HealthCare System Digestive Health

Charlotte, North Carolina, 28204, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212-1375, United States

Location

Texas Digestive Disease Consultants

Southlake, Texas, 76092, United States

Location

University of Utah Health Sciences Center

Salt Lake City, Utah, 84132, United States

Location

UZ Leuven - University Hospital Gasthuisberg

Leuven, 3000, Belgium

Location

GIRI (GI Research Institute)

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

CHU de Rennes - Hopital de Pontchaillou

Rennes, 35033, France

Location

CHU Saint Etienne - Hopital Nord

Saint-Priest-en-Jarez, 42270, France

Location

CHU de Toulouse - Hopital Rangueil

Toulouse, 31059, France

Location

CHRU Nancy Hopital de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Charite Universitatsmedizin Berlin -Campus Virchow Klinikum

Berlin, 13353, Germany

Location

Asklepios Hospital Hamburg - West

Hamburg, 22559, Germany

Location

Praxis fuer Gastroenterologie, Drs. Ehehalt/ Helmstaedter

Heidelberg, 69121, Germany

Location

Universitatsklinikum Jena

Jena, 07747, Germany

Location

Klinikum Mannheim GmbH Universitaetsklinikum

Mannheim, 68167, Germany

Location

Azienda Ospedaliera S. Orsola-Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Policlinico Gemelli

Rome, 00168, Italy

Location

Istituto Clinico Humanitas IRCCS

Rozzano, 20089, Italy

Location

Academic Medical Center

Amsterdam, 1105 AZ, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6229 HX, Netherlands

Location

Hospital Doctor Negrin

Las Palmas de Gran Canaria, 35010, Spain

Location

Hospital Universitario y Politecnico La Fe

Valencia, 46026, Spain

Location

St. Mark's Hospital

Harrow, HA1 3UJ, United Kingdom

Location

Royal London Hospital

London, E1 2EF, United Kingdom

Location

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 39025255 DERIVED

• 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.

  PMID: 36988594 DERIVED

MeSH Terms

Conditions

Pouchitis

Interventions

Ciprofloxacin; vedolizumab

Condition Hierarchy (Ancestors)

Ileitis; Enteritis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Ileal Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2016
• First Posted: June 3, 2016
• Study Start: October 12, 2016
• Primary Completion: June 11, 2020
• Study Completion: February 2, 2021
• Last Updated: February 24, 2022
• Results First Posted: June 30, 2021

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (10); CA (3); ES (2); FR (4); NL (2); GB (3); DE (5); IT (4); BE (1)