Triple Combination Therapy in High Risk Crohn's Disease (CD)
An Open-Label, Phase 4 Study to Evaluate the Efficacy and Safety of Triple Combination Therapy With Vedolizumab IV, Adalimumab SC, and Oral Methotrexate in Early Treatment of Subjects With Crohn's Disease Stratified at Higher Risk for Developing Complications
2 other identifiers
interventional
55
2 countries
32
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_4
Started Apr 2017
Longer than P75 for phase_4
32 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 5, 2016
CompletedFirst Posted
Study publicly available on registry
May 6, 2016
CompletedStudy Start
First participant enrolled
April 18, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 22, 2020
CompletedResults Posted
Study results publicly available
October 21, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
July 5, 2022
CompletedJuly 14, 2023
June 1, 2023
3.4 years
May 5, 2016
September 22, 2021
June 27, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants Achieving Endoscopic Remission at Week 26
Endoscopic remission was defined as simple endoscopic score for Crohn's Disease (SES-CD) scale score from 0-2. The SES-CD evaluated 4 endoscopic variables: ulcer size, proportion of the surface area that was ulcerated, proportion of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was the sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.
Week 26
Secondary Outcomes (19)
Percentage of Participants Achieving Endoscopic Healing at Week 26
Week 26
Percentage of Participants Achieving Endoscopic Response at Week 26
Week 26
Change From Baseline in SES-CD Score at Week 26
Baseline and Week 26
Percentage of Participants Achieving Deep Remission at Week 26
Week 26
Percentage of Participants Achieving Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 26
Week 26
- +14 more secondary outcomes
Study Arms (1)
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)
EXPERIMENTALIn 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.
Interventions
Vedolizumab intravenous infusion.
Adalimumab injection for subcutaneous use.
Methotrexate oral tablets.
Eligibility Criteria
You may qualify if:
- 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.
- 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).
You may not qualify if:
- Has a diagnosis of ulcerative colitis (UC) or indeterminate colitis.
- Has clinical evidence of a current abdominal abscess or a history of prior abdominal abscess.
- Has a known perianal fistula with abscess. (The participant may have a perianal fistula without abscess.)
- Has a known fistula (other than perianal fistula).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (32)
Digestive Health Specialists of the Southeast
Dothan, Alabama, 36305, United States
Gastro Florida
Clearwater, Florida, 33761, United States
Atlanta Gastroenterology Associates
Atlanta, Georgia, 30342-5000, United States
Grand Teton Research Group, PLLC
Idaho Falls, Idaho, 83404, United States
Northshore University HealthSystem
Evanston, Illinois, 60201, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Cotton O'Neil Clinical Research
Topeka, Kansas, 66606, United States
Texas Digestive Disease Consultants Baton Rouge
Baton Rouge, Louisiana, 70809, United States
Louisana Research Center, LLC
Shreveport, Louisiana, 71105, United States
Center for Digestive Health
Troy, Michigan, 48098, United States
Huron Gastroenterology Associates
Ypsilanti, Michigan, 48197, United States
Minnesota Gastroenterology, PA - Plymouth
Plymouth, Minnesota, 55446, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Las Vegas Medical Research
Las Vegas, Nevada, 89113, United States
Icahn School of Medicine at Mt. Sinai
New York, New York, 10029, United States
Digestive Health Partners, PS
Asheville, North Carolina, 28801, United States
Carolinas HealthCare System Digestive Health
Charlotte, North Carolina, 28204, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210, United States
Digestive Disease Specialists, Inc.
Oklahoma City, Oklahoma, 73112, United States
Options Health Research, LLC
Tulsa, Oklahoma, 74104, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Pinnacle Clinical Research
San Antonio, Texas, 78229, United States
Texas Digestive Disease Consultants Southlake
Southlake, Texas, 76092, United States
Tyler Research Institute, LLC
Tyler, Texas, 75701, United States
Texas Digestive Disease Consultants, Webster
Webster, Texas, 77598, United States
University of Utah Health Sciences Center
Salt Lake City, Utah, 84132, United States
Digestive Health Specialists
Tacoma, Washington, 98405, United States
Covenant Health
Edmonton, Alberta, T6L 6K3, Canada
PerCuro Clinical Research Ltd
Victoria, British Columbia, V8V 3M9, Canada
LHSC - Victoria Hospital
London, Ontario, N6A 5W9, Canada
Toronto Digestive Disease Associates Inc
Vaughan, Ontario, L4L 4Y7, Canada
CIUSSS de I'Estrie-CHUS
Sherbrooke, Quebec, J1G 2E8, Canada
Related Publications (1)
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.
PMID: 37743037DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 5, 2016
First Posted
May 6, 2016
Study Start
April 18, 2017
Primary Completion
September 22, 2020
Study Completion
July 5, 2022
Last Updated
July 14, 2023
Results First Posted
October 21, 2021
Record last verified: 2023-06
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.
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.