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NCT06045754PHASE4Recruiting

A Study of Vedolizumab Intravenous (IV) and Adalimumab or Vedolizumab and Ustekinumab in Adults With Crohn's Disease

Takeda

Start Date

4/18/2024

Completion Date

6/28/2027

Summary

The main aim of this study is to learn about the effect of treatment with vedolizumab IV (vedolizumab) together with adalimumab or vedolizumab (VDZ) together with ustekinumab (UST) in adults with moderate to severe Crohn's Disease, and the effect of treatment with vedolizumab alone, after the dual targeted treatment. The study is conducted in two parts. In Part A, participants will receive the dual targeted treatment (vedolizumab together with either adalimumab or ustekinumab). In part B, participants will receive vedolizumab only. Part B will include participants who responded to the treatment in Part A. Each participant will be followed up for at least 26 weeks after the last dose of treatment.

Detailed Description

The drug being tested in this study is vedolizumab. Vedolizumab is being tested to treat people with moderate to severe Crohn's disease who have experienced inadequate response, loss of response or intolerance to either one prior interleukin \[IL\] antagonist, and no other biologic/small molecule (Group A); one IL antagonist and either one Janus kinase inhibitor (JAKi) or one TNFi (other than adalimumab) \[Group B\] (Cohort 1) or one prior tumor necrosis factor inhibitor \[TNFi\] and no other biologic/small molecule (Group C); one TNFi and either 1 JAKi or one IL antagonist (other than UST) (Group D) (Cohort 2). The study will look at the efficacy and safety of dual targeted therapy. The study will enroll approximately 100 participants. Participants will be assigned to one of the two treatment groups in Part A: * Part A, Cohort 1: Vedolizumab + Adalimumab * Part A, Cohort 2: Vedolizumab + Ustekinumab All participants who achieve therapeutic benefit in Part A will receive vedolizumab IV 300 mg monotherapy from Week 30 until Week 46 in Part B. Participants will be followed for a further 20-week safety follow-up period to Week 72 (or 26 weeks post-last dose of study drug). This multi-center trial will be conducted in the United States and Canada. The overall time to participate in this study is approximately 76 weeks.

Eligibility Criteria

Age Range: 18 years to 70 years

Inclusion Criteria: Part A: 1. Has a confirmed diagnosis of CD at least 3 months before screening, based on endoscopy results. 2. Has moderately to severely active CD at Screening, defined as an SES-CD \>=6 (\>=4 if isolated ileal disease). 3. Has demonstrated at least 1 of the following (a, b, or c) to at least 1 IL antagonist or at least 1 tumor necrosis factor (TNF) antagonist, at doses approved for the treatment of CD: 1. Inadequate response after completing the full induction regimen; 2. Loss of response (recurrence of symptoms during scheduled maintenance dosing after prior clinical benefit); or 3. Intolerance (a significant adverse event that precluded further use, including but not limited to serious infection including opportunistic infections, malignancy, infusion-related and hypersensitivity reactions including anaphylaxis, and liver injury). Note: Participants with an inadequate response to \>2 classes of advanced therapies or \>1 agent in the same class are not eligible. Participants who discontinued a third class of advanced therapy for reasons other than inadequate response may be eligible after discussion with the Medical Monitor. Part B: 4. In the investigator's opinion, the participant exhibits a therapeutic benefit at Week 26. Exclusion Criteria: 1. CDAI score \> 450. 2. A current diagnosis of ulcerative colitis or indeterminate colitis. 3. Clinical evidence of an abdominal abscess. 4. Known fistula (other than perianal fistula) or phlegmon. 5. Known perianal fistula with abscess. 6. Ileostomy, colostomy, or severe, or symptomatic stenosis of the intestine. 7. Previous extensive bowel resection with 2 entire segments missing, of the following: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum. 8. Short bowel syndrome. 9. Any planned surgical intervention for CD, except for seton placement for perianal fistula without abscess. 10. History or evidence of adenomatous colonic polyps that have not been removed. 11. History or evidence of colonic mucosal dysplasia. 12. Intolerance or contraindication to ileocolonoscopy. 13. Any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency infection). 14. Active or latent tuberculosis (TB), regardless of treatment history. 15. A positive test for hepatitis B virus (HBV) as defined by the presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) test. 16. A positive test for hepatitis C virus (HCV), as defined by a positive hepatitis C virus antibody (HCVAb) test and detectable HCV ribonucleic acid (RNA). 17. Received approved or investigational anti-integrin antibodies (i.e., vedolizumab, natalizumab, efalizumab, etrolizumab, abrilumab \[AMG 181\], anti- mucosal addressin cell adhesion molecule-1 \[MAdCAM-1\] antibodies, or rituximab) for the treatment of CD. 18. History of or symptoms of progressive multifocal leukoencephalopathy (PML) in the investigator's opinion. If a participant has symptoms consistent with PML, a PML checklist must be completed and submitted to the PML independent adjudication committee. If the PML IAC deems the participant to have PML, the participant is ineligible.

Interventions

DRUG

Vedolizumab

DRUG

Adalimumab

DRUG

Ustekinumab

DRUG

Ustekinumab

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Conditions

Crohn's Disease

Locations

Digestive Health Specialsits

Dothan, Alabama 36301

United States

GI Alliance Sun City

Sun City, Arizona 85351

United States

University of California San Diego Health (UCSD)

La Jolla, California 92037

United States

Cedars-Sinai Medical Center

Los Angeles, California 90048

United States

Hoag Hospital Newport Beach

Newport Beach, California 92663

United States

Medical Research Center of Connecticut, LLC

Hamden, Connecticut 06518

United States

Clinical Research of Osceola

Kissimmee, Florida 34741

United States

Endoscopic Research Inc

Orlando, Florida 32803

United States

Alliance Clinical Research of Tampa, LLC

Tampa, Florida 33615

United States

Gastroenterology Consultants, P.C.

Roswell, Georgia 30076

United States

University of Chicago Medicine

Chicago, Illinois 60637

United States

GI Alliance - Illinois Gastroenterology Group - Glenview

Glenview, Illinois 60026

United States

GI Alliance - Illinois Gastroenterology Group LLC - Gurnee

Gurnee, Illinois 60031

United States

University of Kansas Medical Center

Kansas City, Kansas 66160

United States

Cotton ONeil Clinical Research Center

Topeka, Kansas 66606

United States

University of Louisville

Louisville, Kentucky 40202

United States

GI Alliance

Metairie, Louisiana 70006

United States

Tulane University

New Orleans, Louisiana 70112

United States

Huron Gastroenterology Associates, P.C.

Ypsilanti, Michigan 48197

United States

Mid-America Gastro-Intestinal Consultants

Kansas City, Missouri 64111

United States

BVL Clinical Research

Liberty, Missouri 64068

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

NYU Langone Health

New York, New York 10016

United States

University of Cincinnati

Cincinnati, Ohio 45627

United States

Ohio Gastroenterology group, Inc.

Columbus, Ohio 43202

United States

Great Lakes Gastroenterology Research, LLC

Mentor, Ohio 44060

United States

Gastro Intestinal Research Institute of Northern Ohio, LLC.

Westlake, Ohio 44145

United States

Digestive Disease Specialists, Inc.

Oklahoma City, Oklahoma 73114

United States

Allegheny Health Network

Wexford, Pennsylvania 15090

United States

University Gastroenterology

Providence, Rhode Island 02094

United States

Sanford Health Research

Rapid City, South Dakota 57701

United States

Texas Digestive Disease Consultants Cedar Park

Cedar Park, Texas 78613

United States

GI Alliance - Digestive Health Associates of Texas

Dallas, Texas 75044

United States

The University of Texas Health Science Center at Houston

Houston, Texas 77030

United States

Texas Digestive Disease Consultants Lubbock

Lubbock, Texas 79410

United States

GI Alliance - Mansfield

Mansfield, Texas 76063

United States

Gastroenterology Research of San Antonio, LLC

San Antonio, Texas 78229

United States

Southern Star Research Institute, LLC.

San Antonio, Texas 78229

United States

Texas Digestive Disease Consultants (TDDC), Southlake

Southlake, Texas 76092

United States

Tyler Research Institute, LLC

Tyler, Texas 75701

United States

GI Alliance - Webster

Webster, Texas 77598

United States

University of Utah Health

Salt Lake City, Utah 84108

United States

Washington Gastroenterology- GIA

Bellevue, Washington 98004

United States

Washington Gastroenterology- GIA

Tacoma, Washington 98405

United States

Covenant Health

Edmonton, Alberta T5K 2K4

Canada

London Health Sciences Centre

London, Ontario N6A 5A5

Canada

West GTA Endoscopy Inc.

Mississauga, Ontario L5M 7N4

Canada

Viable Clinical Research - North Bay

North Bay, Ontario P1B 2H3

Canada

Toronto Immune and Digestive Health Institute Inc. (TIDHI)

North York, Ontario M6A3B4

Canada

ABP Research Services Corp.

Oakville, Ontario L6L 5L7

Canada

Taunton Surgical Centre

Oshawa, Ontario L1J 0C7

Canada

Toronto Digestive Disease Associates (TDDA) Inc.

Vaughan, Ontario L4L 4Y7

Canada

The Research Institute of the McGill University Health Centre

Montreal, Quebec H3G 1A4

Canada