PouchitisPhase 4EARNESTNCT02790138
A Study to Evaluate the Efficacy and Safety of Vedolizumab in the Treatment of Chronic Pouchitis
A Phase 4 study testing Ciprofloxacin and Vedolizumab in people with Pouchitis, run by Takeda at 34 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pouchitis
- What is being tested?
- Ciprofloxacin and Vedolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 34 sitesin 9 countries
- Study dates
- 12 Oct 2016to 2 Feb 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 46Show fewer
- Has diverting stoma.
- Infectious Disease Exclusion Criteria 1. Has evidence of an active infection (e.g., sepsis, cytomegalovirus, or listeriosis) during Screening.
- 2. 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).
- OR
- 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)
- General Exclusion Criteria
- Has any prior exposure to vedolizumab, natalizumab, efalizumab, rituximab, etrolizumab, or anti-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) therapy.
- Has a history of hypersensitivity or allergies to vedolizumab or its components.
- 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.
- Is taking, has taken, or is required to take any excluded medications.
- Has received any investigational or approved biologic or biosimilar agent within 60 days prior to Randomization.
- Has received an investigational nonbiologic therapy within 30 days prior to Randomization.
- 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.
- Has received any live vaccinations within 30 days prior to randomization.
- Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist at Screening.
- Has had a kidney, heart, or lung transplant.
- 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.
- Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating, or neurodegenerative disease.
- Has conditions, which in the opinion of the investigator, may interfere with the participant's ability to comply with the study procedures.
- 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.
- Has any of the following laboratory abnormalities during the Screening Period:
- <!-- -->
- Hemoglobin level <8 g/dL.
- White blood cell (WBC) count <3 × 10^9/L.
- Lymphocyte count <0.5 × 10^9/L.
- Platelet count <100 × 10^9/L or >1200 × 10^9/L.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × the upper limit of normal (ULN).
- Alkaline phosphatase >3 × ULN.
- 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.
Trial locations and contacts
34 sites in 9 countries.
34 sites in 9 countries
United States10 sites
University of North Carolina GI
Chapel Hill, North Carolina, 27599
Carolinas HealthCare System Digestive Health
Charlotte, North Carolina, 28204
University of Chicago Medical Center
Chicago, Illinois, 60637
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Northshore University HealthSystem
Evanston, Illinois, 60201
University of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt University Medical Center
Nashville, Tennessee, 37212-1375
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah Health Sciences Center
Salt Lake City, Utah, 84132
Texas Digestive Disease Consultants
Southlake, Texas, 76092
Germany5 sites
Charite Universitatsmedizin Berlin -Campus Virchow Klinikum
Berlin, 13353
Asklepios Hospital Hamburg - West
Hamburg, 22559
Praxis fuer Gastroenterologie, Drs. Ehehalt/ Helmstaedter
Heidelberg, 69121
Universitatsklinikum Jena
Jena, 07747
Klinikum Mannheim GmbH Universitaetsklinikum
Mannheim, 68167
France4 sites
CHU de Rennes - Hopital de Pontchaillou
Rennes, 35033
CHU Saint Etienne - Hopital Nord
Saint-Priest-en-Jarez, 42270
CHU de Toulouse - Hopital Rangueil
Toulouse, 31059
CHRU Nancy Hopital de Brabois
Vandœuvre-lès-Nancy, 54511
Italy4 sites
Azienda Ospedaliera S. Orsola-Malpighi
Bologna, 40138
Azienda Ospedaliera di Padova
Padova, 35128
Policlinico Gemelli
Rome, 00168
Istituto Clinico Humanitas IRCCS
Rozzano, 20089
Canada3 sites
Ottawa Hospital - General Campus
Ottawa, Ontario, K1H 8L6
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
GIRI (GI Research Institute)
Vancouver, British Columbia, V6Z 2K5
United Kingdom3 sites
St. Mark's Hospital
Harrow, HA1 3UJ
Royal London Hospital
London, E1 2EF
John Radcliffe Hospital
Oxford, OX3 9DU
Netherlands2 sites
Academic Medical Center
Amsterdam, 1105 AZ
Maastricht University Medical Center
Maastricht, 6229 HX
Spain2 sites
Hospital Doctor Negrin
Las Palmas de Gran Canaria, 35010
Hospital Universitario y Politecnico La Fe
Valencia, 46026
About this study
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)
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.
Read the 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
- Being tested
- Vedolizumab Placebo, Ciprofloxacin, Vedolizumab
- Keywords
- Drug Therapy
- Medical subject headings
- Pouchitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vedolizumab PlaceboDrug
Vedolizumab placebo-matching IV infusion
CiprofloxacinDrug
Ciprofloxacin tablets
VedolizumabDrug
Also called Entyvio, MLN0002 IV, Kynteles
Vedolizumab IV infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Vedolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 14
Secondary outcomes (9)
Percentage of Participants With Chronic or Recurrent Pouchitis Achieving Clinically Relevant Remission at Week 34
Clinically relevant remission is defined as 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=3 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.
Measured: Week 34
Percentage of Participants Achieving Pouchitis Disease Activity Index (PDAI) Remission at Weeks 14 and 34
PDAI remission is PDAI score <7 and a reduction of PDAI score by ≥3 points from Baseline. The 18-point PDAI score is calculated as a sum of three 6-point scales with total possible subscore of 0 (best) to 6 (worse) and possible total score of 0 (best) to 18 (worse):1)Clinical Symptoms:Stool Frequency(0=usual to postoperative stool frequency to 2=3 or more stools/day>postoperative usual);Rectal bleeding(0=None or rare,1=Present daily);Fecal urgency/abdominal cramps(0=None to 2=Usual),Fever[temperature>37.8 degrees C](0=Absent,1=Present);2)Endoscopic Inflammation:Edema,Granularity,Friability,Loss of vascular pattern,Mucous exudates,Ulcerations. Each item is scored on scale of 0=not present to 1=present summed up to an endoscopic subscore ranging from 0(best) to 6(worst);3) Acute Histologic Inflammation:Polymorphic nuclear leukocyte infiltration(0=None to 3=Severe plus crypt abscess),Ulceration per low power field[mean](0=0% to 3=>50%) where higher scores indicate more severe disease.
Measured: Weeks 14 and 34
Time to PDAI Remission
Time to remission-time in days from start of treatment to PDAI Remission(PDAI score <7 and decrease in PDAI score ≥3 points from Baseline).18-point PDAI score-calculated as sum of 3, 6-point scales with total possible subscore of 0(best) to 6(worse) and possible total score of 0(best)to18(worse):1)Clinical Symptoms:Stool Frequency(0=usual to postoperative stool frequency to 2=3 or more stools/day>postoperative usual);Rectal bleeding(0=None or rare,1=Present daily);Fecal urgency/abdominal cramps(0=None to 2=Usual),Fever[temperature>37.8 degrees C](0=Absent,1=Present);2)Endoscopic Inflammation:Edema,Granularity,Friability,Loss of vascular pattern,Mucous exudates,Ulcerations.Each item is scored on scale of 0=not present to 1=present summed up to an endoscopic subscore=0(best) to 6(worst);3)Acute Histologic Inflammation:Polymorphic nuclear leukocyte infiltration(0=None to 3=Severe plus crypt abscess),Ulceration per low power field[mean](0=0% to 3=>50%),higher scores=more severe disease.
Measured: Baseline up to Week 34
Percentage of Participants Achieving a Partial mPDAI Response at Weeks 14 and 34
Partial mPDAI response is defined as a reduction in 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=3 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. Last observation carried forward (LOCF) method was used for analyses.
Measured: Weeks 14 and 34
Change From Baseline in PDAI Endoscopic Inflammation Subscore at Weeks 14 and 34
The PDAI Endoscopic Inflammation subscore is a sum of scores from findings for Edema, Granularity, Friability, Loss of vascular pattern, Mucous exudates, and Ulcerations, each scored on 0=not present to 1=present scale summed up to a subscore ranging from 0 (best) to 6 (worse) where higher scores = more severe disease. A negative change from Baseline indicates improvement. LOCF method was used for analyses.
Measured: Baseline up to Weeks 14 and 34
Change From Baseline in PDAI Acute Histologic Inflammation Subscore at Weeks 14 and 34
The PDAI Acute Histologic Inflammation subscore is a sum score from findings for Polymorphic nuclear leukocyte infiltration (0=None to 3=Severe plus crypt abscess), and Ulceration per low power field [mean] (0=0% to 3= >50%) summed up to a subscore ranging from 0 (best) to 6 (worse) where higher scores = more severe disease. A negative change from Baseline indicates improvement. LOCF method was used for analyses.
Measured: Baseline up to Weeks 14 and 34
Change From Baseline in Total PDAI Score at Weeks 14 and 34
The 18-point PDAI score is calculated as a sum of three 6-point scales with total possible subscore of 0 (best) to 6 (worse) and possible total score of 0 (best) to 18 (worse):1)Clinical Symptoms:Stool Frequency(0=usual to postoperative stool frequency to 2=3 or more stools/day>postoperative usual);Rectal bleeding(0=None or rare,1=Present daily);Fecal urgency/abdominal cramps(0=None to 2=Usual),Fever[temperature>37.8 degrees C](0=Absent,1=Present);2)Endoscopic Inflammation:Edema,Granularity,Friability,Loss of vascular pattern,Mucous exudates,Ulcerations. Each item is scored on scale of 0=not present to 1=present summed up to an endoscopic subscore ranging from 0(best) to 6(worst);3)Acute Histologic Inflammation:Polymorphic nuclear leukocyte infiltration(0=None to 3=Severe plus crypt abscess),Ulceration per low power field[mean](0=0% to 3=>50%) where higher scores=more severe disease. A negative change from Baseline indicates improvement. LOCF method was used for analyses.
Measured: Baseline up to Weeks 14 and 34
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at 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. A negative change from Baseline indicates worsening. LOCF method was used for analyses.
Measured: Baseline up to Weeks 14, 22, and 34
Change From Baseline in Cleveland Global Quality of Life (CGQL) at 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. The total score ranges from 0 (worst) to 1 (best) where lower scores indicate less quality of life. A negative change from Baseline indicates worsening. LOCF method was used for analyses.
Measured: Baseline up to Weeks 14, 22, and 34
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2016 (estimated)
- Study start12 Oct 2016
- Primary completion11 Jun 2020
- Study completion2 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PouchitisStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02790138
- Sponsor's protocol ID
- Vedolizumab-4004
- Other IDs
- U1111-1171-0918, 2015-003472-78, 2015
- Acronym
- EARNEST
- Status last verified
- Feb 2022
- First submitted
- 26 May 2016
- Last updated
- 24 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Publications
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.
PubMed 39025255Travis 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.
PubMed 36988594
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02790138
- Acronym / sponsor ID
- EARNEST / Vedolizumab-4004
- Conditions
- Pouchitis
- Keywords
- Drug Therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 12 Oct 2016 (actual)
- Primary completion
- 11 Jun 2020 (actual)
- Study completion
- 2 Feb 2021 (actual)
- First posted
- 3 Jun 2016 (estimated)
- Results
- Posted 30 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo IV | Placebo comparator | Drug: Vedolizumab Placebo, Drug: CiprofloxacinVedolizumab 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. |
| Vedolizumab IV 300 mg | Experimental | Drug: VedolizumabVedolizumab 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (46 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vedolizumab PlaceboVedolizumab placebo-matching IV infusion | Drug | Placebo IV |
| CiprofloxacinCiprofloxacin tablets | Drug | Placebo IV |
| VedolizumabAlso: Entyvio, MLN0002 IV, KyntelesVedolizumab IV infusion | Drug | Vedolizumab IV 300 mg |
Primary outcome
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.
9 secondary outcomes
Percentage of Participants With Chronic or Recurrent Pouchitis Achieving Clinically Relevant Remission at Week 34
Time frame: Week 34
Percentage of Participants Achieving Pouchitis Disease Activity Index (PDAI) Remission at Weeks 14 and 34
Time frame: Weeks 14 and 34
Time to PDAI Remission
Time frame: Baseline up to Week 34
Percentage of Participants Achieving a Partial mPDAI Response at Weeks 14 and 34
Time frame: Weeks 14 and 34
Change From Baseline in PDAI Endoscopic Inflammation Subscore at Weeks 14 and 34
Time frame: Baseline up to Weeks 14 and 34
Change From Baseline in PDAI Acute Histologic Inflammation Subscore at Weeks 14 and 34
Time frame: Baseline up to Weeks 14 and 34
Change From Baseline in Total PDAI Score at Weeks 14 and 34
Time frame: Baseline up to Weeks 14 and 34
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 14, 22, and 34
Time frame: Baseline up to Weeks 14, 22, and 34
Change From Baseline in Cleveland Global Quality of Life (CGQL) at Weeks 14, 22, and 34
Time frame: Baseline up to Weeks 14, 22, and 34
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39025255Jairath 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.
- Derived from this study: PubMed 36988594Travis 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.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
34 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ciprofloxacin and Vedolizumab in people with Pouchitis, run by Takeda at 34 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in United States, Germany, France, Italy, Canada and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Chronic or Recurrent Pouchitis Achieving Clinically Relevant Remission at Week 14 (time frame: Week 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02790138, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2022.