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

NCT06045754 | Recruiting Phase 4 DMC FDA Drug

• 3 other identifiers: Vedolizumab-4051MACS-2022-120102EXPLORER 2.0
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 54

Brief 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.

Conditions

Crohn's Disease

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (2)

• Part A: Percentage of Participants With an Endoscopic Response Based on the Simple Endoscopic Score for (SES-CD) at Week 26

  Endoscopic response is defined by a \>=50 percent (%) reduction from baseline in the SES-CD. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of surface area (SA) that is ulcerated, percentage of SA affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is most severe case, with sum of scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease.

  At Week 26

• Part B: Percentage of Participants With an Endoscopic Response Based on the SES-CD at Week 52

  Endoscopic response is defined by a \>=50 reduction from baseline in the SES-CD. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of surface area (SA) that is ulcerated, percentage of SA affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is most severe case, with sum of scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease.

  At Week 52

Secondary Outcomes (16)

• Percentage of Participants in Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) (CDAI <150) at Week 12, Week 26, and Week 52

  At Weeks 12, 26, and 52

• Percentage of Participants in Clinical Remission at Both Week 26 and Week 52

  At Weeks 26 and 52

• Percentage of Participants in 2-item Patient-reported Outcome Measure (PRO2) Remission at Weeks 12, 26, and 52

  At Weeks 12, 26 and 52

• Change in PRO2 Score from Week 26 to 52

  From Week 26 up to Week 52

• Percentage of Participants in Stool Frequency Remission

  At Weeks 12, 26, and 52

Study Arms (3)

Part A, Cohort 1: Vedolizumab + Adalimumab

EXPERIMENTAL

Participants will receive vedolizumab IV 300 mg, at Weeks 0, 2, and 6, then every 8 weeks (Q8W) until Week 22 and adalimumab SC 160, 80, and 40 mg at Weeks 0, 2, and 4, respectively, then 40 mg every 2 weeks (Q2W) until Week 26.

Drug: Vedolizumab; Drug: Adalimumab

Part A, Cohort 2: Vedolizumab + Ustekinumab

EXPERIMENTAL

Participants will receive vedolizumab IV 300 mg, at Weeks 0, 2, and 6, then Q8W until Week 22 and ustekinumab IV 520, 390, or 260 mg (weight-based), then SC 90 mg 8 weeks after initial IV dose, then Q8W until Week 24.

Drug: Vedolizumab; Drug: Ustekinumab

Part B: Vedolizumab Monotherapy

EXPERIMENTAL

Participants who achieve therapeutic benefit in Part A will receive vedolizumab IV 300 mg monotherapy, Q8W from Week 30 until Week 46 and will be followed up to Week 52.

Drug: Vedolizumab

Interventions

Vedolizumab DRUG

Vedolizumab intravenous infusion.

Also known as: Entyvio

Part A, Cohort 1: Vedolizumab + Adalimumab; Part A, Cohort 2: Vedolizumab + Ustekinumab; Part B: Vedolizumab Monotherapy

Adalimumab DRUG

Adalimumab subcutaneous injection.

Also known as: Humira

Part A, Cohort 1: Vedolizumab + Adalimumab

Ustekinumab DRUG

Ustekinumab intravenous infusion.

Also known as: Stelara

Part A, Cohort 2: Vedolizumab + Ustekinumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part A:
• Has a confirmed diagnosis of CD at least 3 months before screening, based on endoscopy results.
• Has moderately to severely active CD at Screening, defined as an SES-CD \>=6 (\>=4 if isolated ileal disease).
• 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:
• Inadequate response after completing the full induction regimen;
• Loss of response (recurrence of symptoms during scheduled maintenance dosing after prior clinical benefit); or
• 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:
• In the investigator's opinion, the participant exhibits a therapeutic benefit at Week 26.

You may not qualify if:

• CDAI score \> 450.
• A current diagnosis of ulcerative colitis or indeterminate colitis.
• Clinical evidence of an abdominal abscess.
• Known fistula (other than perianal fistula) or phlegmon.
• Known perianal fistula with abscess.
• Ileostomy, colostomy, or severe, or symptomatic stenosis of the intestine.
• Previous extensive bowel resection with 2 entire segments missing, of the following: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum.
• Short bowel syndrome.
• Any planned surgical intervention for CD, except for seton placement for perianal fistula without abscess.
• History or evidence of adenomatous colonic polyps that have not been removed.
• History or evidence of colonic mucosal dysplasia.
• Intolerance or contraindication to ileocolonoscopy.
• Any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency infection).
• Active or latent tuberculosis (TB), regardless of treatment history.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (54)

Digestive Health Specialsits

Dothan, Alabama, 36301, United States

RECRUITING

GI Alliance Sun City

Sun City, Arizona, 85351, United States

RECRUITING

University of California San Diego Health (UCSD)

La Jolla, California, 92037, United States

RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Hoag Hospital Newport Beach

Newport Beach, California, 92663, United States

RECRUITING

Medical Research Center of Connecticut, LLC

Hamden, Connecticut, 06518, United States

RECRUITING

Clinical Research of Osceola

Kissimmee, Florida, 34741, United States

RECRUITING

Endoscopic Research Inc

Orlando, Florida, 32803, United States

RECRUITING

University of South Florida

Tampa, Florida, 33612, United States

NOT YET RECRUITING

Alliance Clinical Research of Tampa, LLC

Tampa, Florida, 33615, United States

RECRUITING

Gastroenterology Consultants, P.C.

Roswell, Georgia, 30076, United States

RECRUITING

University of Chicago Medicine

Chicago, Illinois, 60637, United States

RECRUITING

GI Alliance - Illinois Gastroenterology Group - Glenview

Glenview, Illinois, 60026, United States

RECRUITING

GI Alliance - Illinois Gastroenterology Group LLC - Gurnee

Gurnee, Illinois, 60031, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Cotton ONeil Clinical Research Center

Topeka, Kansas, 66606, United States

RECRUITING

University of Louisville

Louisville, Kentucky, 40202, United States

RECRUITING

GI Alliance

Metairie, Louisiana, 70006, United States

RECRUITING

Tulane University

New Orleans, Louisiana, 70112, United States

RECRUITING

Huron Gastroenterology Associates, P.C.

Ypsilanti, Michigan, 48197, United States

RECRUITING

Mid-America Gastro-Intestinal Consultants

Kansas City, Missouri, 64111, United States

RECRUITING

BVL Clinical Research

Liberty, Missouri, 64068, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45627, United States

RECRUITING

Ohio Gastroenterology group, Inc.

Columbus, Ohio, 43202, United States

RECRUITING

Great Lakes Gastroenterology Research, LLC

Mentor, Ohio, 44060, United States

RECRUITING

Gastro Intestinal Research Institute of Northern Ohio, LLC.

Westlake, Ohio, 44145, United States

RECRUITING

Digestive Disease Specialists, Inc.

Oklahoma City, Oklahoma, 73114, United States

RECRUITING

Allegheny Health Network

Wexford, Pennsylvania, 15090, United States

RECRUITING

University Gastroenterology

Providence, Rhode Island, 02905, United States

RECRUITING

Rapid City Medical Center, LLP

Rapid City, South Dakota, 57701, United States

RECRUITING

Texas Digestive Disease Consultants Cedar Park

Cedar Park, Texas, 78613, United States

RECRUITING

GI Alliance - Digestive Health Associates of Texas

Dallas, Texas, 75044, United States

RECRUITING

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

Texas Digestive Disease Consultants Lubbock

Lubbock, Texas, 79410, United States

RECRUITING

GI Alliance - Mansfield

Mansfield, Texas, 76063, United States

RECRUITING

Gastroenterology Research of San Antonio, LLC

San Antonio, Texas, 78229, United States

RECRUITING

Southern Star Research Institute, LLC.

San Antonio, Texas, 78229, United States

RECRUITING

Texas Digestive Disease Consultants (TDDC), Southlake

Southlake, Texas, 76092, United States

RECRUITING

Tyler Research Institute, LLC

Tyler, Texas, 75701, United States

RECRUITING

GI Alliance - Webster

Webster, Texas, 77598, United States

RECRUITING

University of Utah Health

Salt Lake City, Utah, 84108, United States

RECRUITING

Washington Gastroenterology- GIA

Bellevue, Washington, 98004, United States

WITHDRAWN

Washington Gastroenterology- GIA

Tacoma, Washington, 98405, United States

RECRUITING

Covenant Health

Edmonton, Alberta, T5K 2K4, Canada

RECRUITING

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

RECRUITING

West GTA Endoscopy Inc.

Mississauga, Ontario, L5M 7N4, Canada

RECRUITING

Viable Clinical Research - North Bay

North Bay, Ontario, P1B 2H3, Canada

RECRUITING

Toronto Immune and Digestive Health Institute Inc. (TIDHI)

North York, Ontario, M6A3B4, Canada

RECRUITING

ABP Research Services Corp.

Oakville, Ontario, L6L 5L7, Canada

RECRUITING

Taunton Surgical Centre

Oshawa, Ontario, L1J 0C7, Canada

WITHDRAWN

Toronto Digestive Disease Associates (TDDA) Inc.

Vaughan, Ontario, L4L 4Y7, Canada

RECRUITING

The Research Institute of the McGill University Health Centre

Montreal, Quebec, H3G 1A4, Canada

RECRUITING

Related Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.

MeSH Terms

Conditions

Crohn Disease

Interventions

vedolizumab; Adalimumab; Ustekinumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Central Study Contacts

Takeda Contact

CONTACT

+1-877-825-3327; medinfoUS@takeda.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2023
• First Posted: September 21, 2023
• Study Start: April 18, 2024
• Primary Completion (Estimated): June 28, 2027
• Study Completion (Estimated): June 28, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

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 (45); CA (9)