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NCT02790138: EARNEST

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

Completed Phase 4 Results posted Last updated 24 February 2022
What this trial tests

Phase 4 trial testing Vedolizumab Placebo in Pouchitis in 102 participants. Completed in 2 February 2021.

Timeline
12 October 2016
Primary endpoint
11 June 2020
2 February 2021

Quick facts

Lead sponsorTakeda
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment102
Start date12 October 2016
Primary completion11 June 2020
Estimated completion2 February 2021
Sites34 locations across France, Italy, Netherlands, Belgium, United Kingdom, Germany, Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

Takeda — full company profile →

Who can join

Adults 18 to 80, any sex, with Pouchitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Chronic or Recurrent Pouchitis Achieving Clinically Relevant Remission at Week 14 Primary · 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 sympto

GroupValue95% CI
Placebo IV9.83.3 – 21.4
Vedolizumab IV 300 mg31.419.1 – 45.9
Percentage of Participants With Chronic or Recurrent Pouchitis Achieving Clinically Relevant Remission at Week 34 Secondary · 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) Endosco

GroupValue95% CI
Placebo IV17.68.4 – 30.9
Vedolizumab IV 300 mg35.322.4 – 49.9
Percentage of Participants Achieving Pouchitis Disease Activity Index (PDAI) Remission at Weeks 14 and 34 Secondary · 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,Friabilit

Week 14
GroupValue95% CI
Placebo IV9.83.3 – 21.4
Vedolizumab IV 300 mg35.322.4 – 49.9
Week 34
GroupValue95% CI
Placebo IV17.68.4 – 30.9
Vedolizumab IV 300 mg37.324.1 – 51.9
Time to PDAI Remission Secondary · Baseline up to Week 34

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 Inflammat

GroupValue95% CI
Placebo IVNANA – NA
Vedolizumab IV 300 mg239.0101.0 – NA
Percentage of Participants Achieving a Partial mPDAI Response at Weeks 14 and 34 Secondary · 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: Ed

Week 14
GroupValue95% CI
Placebo IV33.320.8 – 47.9
Vedolizumab IV 300 mg62.748.1 – 75.9
Week 34
GroupValue95% CI
Placebo IV29.417.5 – 43.8
Vedolizumab IV 300 mg51.036.6 – 65.2
Change From Baseline in PDAI Endoscopic Inflammation Subscore at Weeks 14 and 34 Secondary · Baseline up to 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.

Baseline
GroupValue95% CI
Placebo IV4.5± 1.36
Vedolizumab IV 300 mg4.6± 1.15
Change from Baseline at Week 14
GroupValue95% CI
Placebo IV-0.2± 1.36
Vedolizumab IV 300 mg-1.1± 1.59
Change from Baseline at Week 34
GroupValue95% CI
Placebo IV-0.6± 1.86
Vedolizumab IV 300 mg-1.2± 1.87
Change From Baseline in PDAI Acute Histologic Inflammation Subscore at Weeks 14 and 34 Secondary · Baseline up to 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.

Baseline
GroupValue95% CI
Placebo IV2.6± 1.39
Vedolizumab IV 300 mg2.5± 1.42
Change from Baseline at Week 14
GroupValue95% CI
Placebo IV-0.1± 1.33
Vedolizumab IV 300 mg-0.4± 1.98
Change from Baseline at Week 34
GroupValue95% CI
Placebo IV-0.2± 1.52
Vedolizumab IV 300 mg-0.2± 2.03
Change From Baseline in Total PDAI Score at Weeks 14 and 34 Secondary · Baseline up to 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=n

Baseline
GroupValue95% CI
Placebo IV10.5± 2.48
Vedolizumab IV 300 mg10.5± 2.20
Change from Baseline at Week 14
GroupValue95% CI
Placebo IV-1.3± 2.68
Vedolizumab IV 300 mg-2.7± 3.86
Change from Baseline at Week 34
GroupValue95% CI
Placebo IV-1.6± 3.41
Vedolizumab IV 300 mg-2.9± 3.93
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 14, 22, and 34 Secondary · Baseline up to 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

Baseline
GroupValue95% CI
Placebo IV131.5± 30.78
Vedolizumab IV 300 mg137.9± 33.53
Change from Baseline at Week 14
GroupValue95% CI
Placebo IV14.6± 26.67
Vedolizumab IV 300 mg18.3± 29.20
Change from Baseline at Week 22
GroupValue95% CI
Placebo IV16.0± 29.12
Vedolizumab IV 300 mg21.3± 31.28
Change from Baseline at Week 34
GroupValue95% CI
Placebo IV10.4± 25.98
Vedolizumab IV 300 mg24.4± 34.21
Change From Baseline in Cleveland Global Quality of Life (CGQL) at Weeks 14, 22, and 34 Secondary · Baseline up to 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.

Baseline
GroupValue95% CI
Placebo IV0.522± 0.1953
Vedolizumab IV 300 mg0.556± 0.1626
Change from Baseline at Week 14
GroupValue95% CI
Placebo IV0.051± 0.1518
Vedolizumab IV 300 mg0.088± 0.1715
Change from Baseline at Week 22
GroupValue95% CI
Placebo IV0.073± 0.1491
Vedolizumab IV 300 mg0.093± 0.1648
Change from Baseline at Week 34
GroupValue95% CI
Placebo IV0.056± 0.1544
Vedolizumab IV 300 mg0.083± 0.1831

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug up to 18 weeks after last dose (Up to 50 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo IV
Serious: 4/51 (8%)
Deaths: 0/51
Vedolizumab IV 300 mg
Serious: 3/51 (6%)
Deaths: 0/51

Serious adverse events (5 terms)

ReactionSystemPlacebo IVVedolizumab IV 300 mg
PouchitisGastrointestinal disorders
Abdominal painGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
GastroenteritisInfections and infestations
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (12 terms — click to expand)

ReactionSystemPlacebo IVVedolizumab IV 300 mg
PouchitisGastrointestinal disorders
HeadacheNervous system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
NasopharyngitisInfections and infestations
NauseaGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
Upper respiratory tract infectionInfections and infestations
Abdominal painGastrointestinal disorders
Frequent bowel movementsGastrointestinal disorders
InfluenzaInfections and infestations
GastroenteritisInfections and infestations
DyspnoeaRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Pouchitis, Abdominal pain, Intestinal obstruction, Gastroenteritis, Basal cell carcinoma.

Data from ClinicalTrials.gov NCT02790138 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Perspectives on Current and Novel Treatments for Inflammatory Bowel Disease.
    Na SY, Moon W. · · 2019 · cited 99× · PMID 31195433 · DOI 10.5009/gnl19019
  2. Vedolizumab for the Treatment of Chronic Pouchitis.
    Travis S, Silverberg MS, Danese S, Gionchetti P, et al · · 2023 · cited 81× · PMID 36988594 · DOI 10.1056/nejmoa2208450
  3. Outcome of biological therapies in chronic antibiotic-refractory pouchitis: A retrospective single-centre experience.
    Verstockt B, Claeys C, De Hertogh G, Van Assche G, et al · · 2019 · cited 40× · PMID 31700634 · DOI 10.1177/2050640619871797
  4. Medical treatment of pouchitis: a guide for the clinician.
    Rabbenou W, Chang S. · · 2021 · cited 11× · PMID 34249146 · DOI 10.1177/17562848211023376
  5. Mucosal Healing With Vedolizumab in Patients With Chronic Pouchitis: EARNEST, a Randomized, Double-Blind, Placebo-Controlled Trial.
    Jairath V, Feagan BG, Silverberg MS, Danese S, et al · · 2025 · cited 7× · PMID 39025255 · DOI 10.1016/j.cgh.2024.06.037
  6. Chronic Antibiotic-Refractory Pouchitis: Management Challenges.
    Outtier A, Ferrante M. · · 2021 · cited 6× · PMID 34163205 · DOI 10.2147/ceg.s219556
  7. UEG Week 2019 Poster Presentations.
    · 2019 · cited 5× · PMID 32213001 · DOI 10.1177/2050640619854671
  8. Ileal Pouch-Anal Anastomosis in the Older Adult: a Review of Postoperative Outcomes and Pouchitis Treatment.
    Chen SL, Faye AS, Chang S. · · 2022 · cited 3× · PMID 36844648 · DOI 10.1007/s11938-022-00405-x

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02790138.

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