Effect of Intravenous (IV) Vedolizumab on Mucosal Healing in Crohn's Disease

NCT02425111 | Completed Phase 3 Results

• 4 other identifiers: MLN0002-3028U1111-1159-58062014-003509-13183974
• Study Type: interventional
• Target: 101
• Locations: 8 countries
• Sites: 79

Brief Summary

The purpose of this study is to evaluate endoscopic remission at Week 26 as assessed by ileocolonoscopy.

Conditions

Crohn's Disease

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Part A: Percentage of Participants Achieving Endoscopic Remission at Week 26

  Endoscopic remission is defined as a simple endoscopic score for Crohn's Disease (SES-CD) score of ≤4. The SES-CD evaluates 4 endoscopic variables (ulcer size, proportion of the surface area that is ulcerated, proportion of the surface area affected, and stenosis in 5 segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable is the sum of values obtained for each segment. The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

  Week 26

Secondary Outcomes (14)

• Part A: Percentage of Participants Achieving Complete Mucosal Healing at Week 26

  Week 26

• Part B: Percentage of Participants Achieving Complete Mucosal Healing at Week 52

  Week 52

• Part A: Percentage of Participants Achieving Endoscopic Remission at Week 14

  Week 14

• Part B: Percentage of Participants Achieving Endoscopic Remission at Week 52

  Week 52

• Part A: Percentage of Participants With Endoscopic Response at Week 14

  Baseline and Week 14

Study Arms (1)

Vedolizumab 300 mg

EXPERIMENTAL

Part A: Vedolizumab 300 mg, intravenously (IV), once on Day 1 and Weeks 2, 6, 14 and 22, followed by Part B: Vedolizumab 300 mg, intravenously (IV), once at Weeks 30, 38, and 46.

Drug: Vedolizumab

Interventions

Vedolizumab DRUG

Vedolizumab intravenous injection

Also known as: MLN0002

Vedolizumab 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.
• Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Has a diagnosis of moderately to severely active Crohn's disease (CD) at least 3 months prior to enrollment, with a Crohn's Disease Activity Index (CDAI) score of 220-450 during the Screening Period, a simple endoscopic score for Crohn's Disease (SES-CD) score of ≥7 and presence of at least one mucosal ulceration documented by recorded ileocolonoscopy at Screening assessed by the central reader.
• Has CD with involvement of the ileum and/or colon that can be assessed by ileocolonoscopy.
• Is male or female and aged 18 to 80 years, inclusive.
• A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
• A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
• Has demonstrated an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents as defined below:
• Immunomodulators:
• i. Has signs and symptoms of persistently active disease despite a history of at least one 12-week regimen of oral azathioprine (≥1.5 mg/kg) or 6-mercaptopurine (≥0.75 mg/kg), OR ii. Has a history of intolerance (including but not limited to nausea/vomiting, abdominal pain, pancreatitis, liver function test abnormalities, lymphopenia, thiopurine S-methyltransferase non wild type \[where wild type is defined as thiopurine S-methyltransferase (TPMT)\*1/\*1\], infection) to at least 1 immunomodulator.
• Tumor necrosis factor- alpha (TNF-α) antagonists:
• i. Has signs and symptoms of persistently active disease despite a history of at least 1 induction with:
• Infliximab: 4-week regimen of 5 mg/kg, 2 doses at 2 weeks apart, OR
• Adalimumab: 2-week regimen of 160 mg on Day 1 and 80 mg on Day 15, OR
• Certolizumab: 4-week regimen of 400 mg initially at Weeks 0, 2, 4 OR ii. Has recurrence of symptoms during maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not qualify), OR iii. Has a history of intolerance of infliximab, adalimumab, or certolizumab, including but not limited to, infusion-related reaction, demyelination, congestive heart failure, or infection.

You may not qualify if:

• Has received a diagnosis of ulcerative colitis or indeterminate colitis.
• Has clinical evidence of abdominal abscess.
• Has a history of \>3 small bowel resections or diagnosis of short bowel syndrome.
• Has extensive colonic resection, ie, subtotal or total colectomy with \<15 cm colon remaining.
• Has ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
• Has a history or evidence of adenomatous colonic polyps that have not been removed.
• Has a history or evidence of colonic mucosal dysplasia.
• Has intolerance or contraindication to undergo ileocolonoscopy.
• Has active or latent tuberculosis, regardless of treatment history, as evidenced by any of the following:
• a. History of tuberculosis (TB). b. A diagnostic TB test performed during screening that is positive, as defined by: i. A positive QuantiFERON® test or 2 successive indeterminate QuantiFERON tests OR ii. A tuberculin skin test reaction ≥10 mm (≥5 mm in participants receiving the equivalent of \>15 mg/day prednisone).
• Has chronic hepatitis B (HBV) or hepatitis C (HCV) infection.
• Has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus \[HIV\] infection, organ transplantation).
• Has evidence of active C. difficile infection or is having treatment for C. difficile infection or other intestinal pathogens during Screening.
• Has evidence of an active infection during Screening.
• Currently requires or has a planned surgical intervention for CD during the study.

Sponsors & Collaborators

• Takeda: lead

Study Sites (79)

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La Jolla, California, United States

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Hamden, Connecticut, United States

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Gainesville, Florida, United States

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Inverness, Florida, United States

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Maitland, Florida, United States

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Miami, Florida, United States

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Winter Park, Florida, United States

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Macon, Georgia, United States

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Suwanee, Georgia, United States

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Topeka, Kansas, United States

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Baton Rouge, Louisiana, United States

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Columbia, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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St Louis, Missouri, United States

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Manhasset, New York, United States

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Poughkeepsie, New York, United States

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Winston-Salem, North Carolina, United States

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Cleveland, Ohio, United States

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Tulsa, Oklahoma, United States

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Portland, Oregon, United States

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Germantown, Tennessee, United States

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Bonheiden, Belgium

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Brussels, Belgium

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Herentals, Belgium

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Kortrijk, Belgium

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Leuven, Belgium

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Roeselare, Belgium

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Vancouver, British Columbia, Canada

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Victoria, British Columbia, Canada

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Halifax, Nova Scotia, Canada

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London, Ontario, Canada

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Vaughan, Ontario, Canada

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Hradec Králové, Czechia

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Kladno, Czechia

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Pardubice, Czechia

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Prague, Czechia

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Nice, Alpes Maritimes, France

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Pessac, Gironde, France

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Reims, Marne, France

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Lille, Nord, France

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Saint-Étienne-de-Montluc, Pays de la Loire Region, France

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Lille, France

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Nantes, France

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Nice, France

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Pessac, France

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Reims, France

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Saint-Etienne, France

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Toulouse, France

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Békéscsaba, Hungary

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Budapest, Hungary

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Debrecen, Hungary

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Gyöngyös, Hungary

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Gyula, Hungary

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Jászberény, Hungary

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Kistarcsa, Hungary

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Miskolc, Hungary

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Mosonmagyaróvár, Hungary

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Pécs, Hungary

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Szeged, Hungary

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Szekszárd, Hungary

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Székesfehérvár, Hungary

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Vác, Hungary

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San Giovanni Rotondo, Foggia, Italy

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Rozzano, Milano, Italy

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San Donato Milanese, Milano, Italy

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Bologna, Italy

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Florence, Italy

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Napoli, Italy

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Padua, Italy

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Roma, Italy

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Rozzano, Italy

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San Donato Milanese, Italy

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San Giovanni Rotondo, Italy

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Bialystok, Poland

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Elblag, Poland

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Poznan, Poland

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Warsaw, Poland

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Wroclaw, Poland

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Related Publications (3)

• Rimola J, Colombel JF, Bressler B, Adsul S, Siegelman J, Cole PE, Lindner D, Danese S. Magnetic Resonance Enterography Assessment of Transmural Healing with Vedolizumab in Moderate to Severe Crohn's Disease: Feasibility in the VERSIFY Phase 3 Clinical Trial. Clin Exp Gastroenterol. 2024 Jan 27;17:9-23. doi: 10.2147/CEG.S429039. eCollection 2024.

  PMID: 38298861 DERIVED

• Narula N, Wong ECL, Dulai PS, Marshall JK, Jairath V, Reinisch W. Comparative Effectiveness of Biologics for Endoscopic Healing of the Ileum and Colon in Crohn's Disease. Am J Gastroenterol. 2022 Jul 1;117(7):1106-1117. doi: 10.14309/ajg.0000000000001795. Epub 2022 Apr 15.

  PMID: 35435862 DERIVED

• Danese S, Sandborn WJ, Colombel JF, Vermeire S, Glover SC, Rimola J, Siegelman J, Jones S, Bornstein JD, Feagan BG. Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn's Disease. Gastroenterology. 2019 Oct;157(4):1007-1018.e7. doi: 10.1053/j.gastro.2019.06.038. Epub 2019 Jul 4.

  PMID: 31279871 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2015
• First Posted: April 23, 2015
• Study Start: March 30, 2015
• Primary Completion: June 2, 2017
• Study Completion: February 21, 2018
• Last Updated: September 14, 2018
• Results First Posted: September 14, 2018

Record last verified: 2018-08

Locations

IT (11); BE (6); CZ (4); US (22); FR (12); CA (5); PL (5); HU (14)