Clinical trial NCT02764762: Triple Combination Therapy in High Risk Crohn's Disease (CD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Crohn Disease
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-05-06
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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:

Gastrointestinal (GI) 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).

Primary outcomes:
measure: Percentage of Participants Achieving Endoscopic Remission at Week 26
timeFrame: Week 26
Secondary outcomes:
measure: Percentage of Participants Achieving Endoscopic Healing at Week 26
timeFrame: Week 26
measure: Percentage of Participants Achieving Endoscopic Response at Week 26
timeFrame: Week 26
measure: Change From Baseline in SES-CD Score at Week 26
timeFrame: Baseline and Week 26
measure: Percentage of Participants Achieving Deep Remission at Week 26
timeFrame: Week 26
measure: Percentage of Participants Achieving Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 26
timeFrame: Week 26
measure: Percentage of Participants Achieving Clinical Remission at Weeks 10 and 26
timeFrame: Weeks 10 and 26
measure: Percentage of Participants Achieving Clinical Response at Weeks 10 and 26
timeFrame: Weeks 10 and 26
measure: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 10 and 26
timeFrame: Baseline, Weeks 10 and 26
measure: Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102
timeFrame: Baseline, Weeks 10, 14, 26, 52, 78 and 102
measure: Percentage of Participants Achieving Clinical Remission and CRP <5 Milligram Per Liter (mg/L) at Weeks 26, 52, 78, and 102
timeFrame: Weeks 26, 52, 78 and 102
measure: Percentage of Participants Using Oral Corticosteroids at Baseline Who Have Discontinued Corticosteroids and Are in Clinical Remission at Weeks 10, 26, and 102
timeFrame: Weeks 10, 26 and 102
measure: Percentage of Participants Maintaining Clinical Remission at Weeks 52, 78, and 102
timeFrame: Weeks 52, 78 and 102
measure: Percentage of Participants Maintaining Clinical Response at Weeks 52, 78, and 102
timeFrame: Weeks 52, 78 and 102
measure: Percentage of Participants Maintaining Endoscopic Remission at Week 102
timeFrame: Week 102
measure: Percentage of Participants Maintaining Deep Remission at Week 102
timeFrame: Week 102
measure: Percentage of Participants Maintaining Endoscopic Healing at Week 102
timeFrame: Week 102
measure: Percentage of Participants Maintaining Endoscopic Response at Week 102
timeFrame: Week 102
measure: Percentage of Participants Maintaining Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 102
timeFrame: Week 102
measure: Percentage of Participants With First Exacerbation of CD
timeFrame: After 26 Weeks up to Week 120
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialists of the Southeast
state: Alabama
city: Clearwater
country: United States
facility: Gastro Florida
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Idaho Falls
country: United States
facility: Grand Teton Research Group, PLLC
state: Idaho
city: Evanston
country: United States
facility: Northshore University HealthSystem
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Topeka
country: United States
facility: Cotton O'Neil Clinical Research
state: Kansas
city: Baton Rouge
country: United States
facility: Texas Digestive Disease Consultants Baton Rouge
state: Louisiana
city: Shreveport
country: United States
facility: Louisana Research Center, LLC
state: Louisiana
city: Troy
country: United States
facility: Center for Digestive Health
state: Michigan
city: Ypsilanti
country: United States
facility: Huron Gastroenterology Associates
state: Michigan
city: Plymouth
country: United States
facility: Minnesota Gastroenterology, PA - Plymouth
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Las Vegas
country: United States
facility: Las Vegas Medical Research
state: Nevada
city: New York
country: United States
facility: Icahn School of Medicine at Mt. Sinai
state: New York
city: Asheville
country: United States
facility: Digestive Health Partners, PS
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas HealthCare System Digestive Health
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Digestive Disease Specialists, Inc.
state: Oklahoma
city: Tulsa
country: United States
facility: Options Health Research, LLC
state: Oklahoma
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants Southlake
state: Texas
city: Tyler
country: United States
facility: Tyler Research Institute, LLC
state: Texas
city: Webster
country: United States
facility: Texas Digestive Disease Consultants, Webster
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Tacoma
country: United States
facility: Digestive Health Specialists
state: Washington
city: Edmonton
country: Canada
facility: Covenant Health
state: Alberta
city: Victoria
country: Canada
facility: PerCuro Clinical Research Ltd
state: British Columbia
city: London
country: Canada
facility: LHSC - Victoria Hospital
state: Ontario
city: Vaughan
country: Canada
facility: Toronto Digestive Disease Associates Inc
state: Ontario
city: Sherbrooke
country: Canada
facility: CIUSSS de I'Estrie-CHUS
state: Quebec
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: