Triple Combination Therapy in High Risk Crohn's Disease (CD)

NCT ID: NCT02764762

Last Updated: 2023-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-18
• Study Completion Date: 2022-07-05

Brief Summary

The purpose of this study is to determine the effect of triple combination therapy with an anti-integrin (vedolizumab intravenous [IV]), a tumor necrosis factor (TNF) antagonist (adalimumab subcutaneously [SC]), and an immunomodulator (oral methotrexate) on endoscopic remission in participants with newly-diagnosed CD stratified at higher risk for complications.

Detailed Description

The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have CD. This study will look at the endoscopic remission and mucosal healing of gastrointestinal tract of people who take vedolizumab as triple combination therapy with adalimumab and methotrexate.

The study will enroll approximately 60 participants. Participants will receive triple combination therapy which includes:

• Vedolizumab 300 mg (intravenous)
• Adalimumab 160/80/40 mg (subcutaneous)
• Methotrexate 15 mg (oral)

All participants will receive vedolizumab intravenous infusion on Weeks 0, 2, 6, 14 and 22 along with adalimumab 160 mg, subcutaneous injection at Week 0, 80 mg at Week 2, then 40 mg once at Week 4 and every 2 weeks thereafter until Week 26 along with methotrexate tablets orally, once weekly from Weeks 0 up to Week 34. In monotherapy phase, all participants will receive vedolizumab intravenous infusion once at Weeks 30, 38, 46, 54, 62, 70, 78, 86, 94 and 102.

This multi-center trial will be conducted in the United States and Canada. The overall time to participate in this study is 128 weeks. Participants will make multiple visits to the clinic, plus a final visit 18 weeks after last dose of study drug for a safety follow-up assessment. Participants will also participate in a long-term safety questionnaire, by phone, at 26 weeks (6 months) from the last dose of study drug.

Conditions

Crohn Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)

In Triple Combination Therapy Phase, vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2, 6, 14 and 22, with adalimumab 160 mg subcutaneously (SC), once at Week 0, then 80 mg once at Week 2, then 40 mg once at Week 4 and every 2 weeks thereafter until Week 26 along with oral methotrexate 15 mg tablets orally once weekly from Weeks 0 up to Week 34. In Monotherapy Phase, vedolizumab 300 mg IV infusion once at Weeks 30, 38, 46, 54, 62, 70, 78, 86, 94 and 102.

Group Type: EXPERIMENTAL

Vedolizumab

Intervention Type: DRUG

Vedolizumab intravenous infusion.

Adalimumab

Intervention Type: DRUG

Adalimumab injection for subcutaneous use.

Methotrexate

Intervention Type: DRUG

Methotrexate oral tablets.

Interventions

Vedolizumab

Vedolizumab intravenous infusion.

Intervention Type: DRUG

Adalimumab

Adalimumab injection for subcutaneous use.

Intervention Type: DRUG

Methotrexate

Methotrexate oral tablets.

Intervention Type: DRUG

Other Intervention Names

Entyvio; MLN0002 IV; Humira

Eligibility Criteria

Inclusion Criteria

1. Has an initial diagnosis of CD established within 24 months prior to screening with involvement of the ileum and/or colon that can be assessed by ileocolonoscopy.

2. Has moderate to severely active CD during Screening defined by a centrally assessed simple endoscopic score for Crohn disease (SES-CD) score >=7 (or >=4 if isolated ileal disease).

Exclusion Criteria

1. Has a diagnosis of ulcerative colitis (UC) or indeterminate colitis.

2. Has clinical evidence of a current abdominal abscess or a history of prior abdominal abscess.

3. Has a known perianal fistula with abscess. (The participant may have a perianal fistula without abscess.)

4. Has a known fistula (other than perianal fistula).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Digestive Health Specialists of the Southeast

Dothan, Alabama, United States

Gastro Florida

Clearwater, Florida, United States

Atlanta Gastroenterology Associates

Atlanta, Georgia, United States

Grand Teton Research Group, PLLC

Idaho Falls, Idaho, United States

Northshore University HealthSystem

Evanston, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Cotton O'Neil Clinical Research

Topeka, Kansas, United States

Texas Digestive Disease Consultants Baton Rouge

Baton Rouge, Louisiana, United States

Louisana Research Center, LLC

Shreveport, Louisiana, United States

Center for Digestive Health

Troy, Michigan, United States

Huron Gastroenterology Associates

Ypsilanti, Michigan, United States

Minnesota Gastroenterology, PA - Plymouth

Plymouth, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Las Vegas Medical Research

Las Vegas, Nevada, United States

Icahn School of Medicine at Mt. Sinai

New York, New York, United States

Digestive Health Partners, PS

Asheville, North Carolina, United States

Carolinas HealthCare System Digestive Health

Charlotte, North Carolina, United States

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Digestive Disease Specialists, Inc.

Oklahoma City, Oklahoma, United States

Options Health Research, LLC

Tulsa, Oklahoma, United States

Baylor College of Medicine

Houston, Texas, United States

Pinnacle Clinical Research

San Antonio, Texas, United States

Texas Digestive Disease Consultants Southlake

Southlake, Texas, United States

Tyler Research Institute, LLC

Tyler, Texas, United States

Texas Digestive Disease Consultants, Webster

Webster, Texas, United States

University of Utah Health Sciences Center

Salt Lake City, Utah, United States

Digestive Health Specialists

Tacoma, Washington, United States

Covenant Health

Edmonton, Alberta, Canada

PerCuro Clinical Research Ltd

Victoria, British Columbia, Canada

LHSC - Victoria Hospital

London, Ontario, Canada

Toronto Digestive Disease Associates Inc

Vaughan, Ontario, Canada

CIUSSS de I'Estrie-CHUS

Sherbrooke, Quebec, Canada

Countries

United States; Canada

References

Colombel JF, Ungaro RC, Sands BE, Siegel CA, Wolf DC, Valentine JF, Feagan BG, Neustifter B, Kadali H, Nazarey P, James A, Jairath V, Qasim Khan RM. Vedolizumab, Adalimumab, and Methotrexate Combination Therapy in Crohn's Disease (EXPLORER). Clin Gastroenterol Hepatol. 2024 Jul;22(7):1487-1496.e12. doi: 10.1016/j.cgh.2023.09.010. Epub 2023 Sep 22.

Reference Type: DERIVED

PMID: 37743037 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1175-9094

Identifier Type: REGISTRY

Identifier Source: secondary_id

Vedolizumab-4006

Identifier Type: -

Identifier Source: org_study_id