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
Overview
- Phase
- Phase 4
- Intervention
- Vedolizumab
- Conditions
- Crohn Disease
- Sponsor
- Takeda
- Enrollment
- 55
- Locations
- 32
- Primary Endpoint
- Percentage of Participants Achieving Endoscopic Remission at Week 26
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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).
Exclusion Criteria
- •Gastrointestinal (GI) Exclusion Criteria
- •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).
Arms & Interventions
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.
Intervention: Vedolizumab
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.
Intervention: Adalimumab
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.
Intervention: Methotrexate
Outcomes
Primary Outcomes
Percentage of Participants Achieving Endoscopic Remission at Week 26
Time Frame: 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.
Secondary Outcomes
- Change From Baseline in SES-CD Score at Week 26(Baseline and Week 26)
- Percentage of Participants Using Oral Corticosteroids at Baseline Who Have Discontinued Corticosteroids and Are in Clinical Remission at Weeks 10, 26, and 102(Weeks 10, 26 and 102)
- Percentage of Participants Maintaining Clinical Remission at Weeks 52, 78, and 102(Weeks 52, 78 and 102)
- Percentage of Participants Maintaining Clinical Response at Weeks 52, 78, and 102(Weeks 52, 78 and 102)
- Percentage of Participants Maintaining Endoscopic Remission at Week 102(Week 102)
- Percentage of Participants Achieving Endoscopic Healing at Week 26(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)
- Percentage of Participants Achieving Clinical Remission at Weeks 10 and 26(Weeks 10 and 26)
- Percentage of Participants Achieving Clinical Response at Weeks 10 and 26(Weeks 10 and 26)
- Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 10 and 26(Baseline, Weeks 10 and 26)
- Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102(Baseline, Weeks 10, 14, 26, 52, 78 and 102)
- Percentage of Participants Achieving Clinical Remission and CRP <5 Milligram Per Liter (mg/L) at Weeks 26, 52, 78, and 102(Weeks 26, 52, 78 and 102)
- Percentage of Participants Achieving Endoscopic Response at Week 26(Week 26)
- Percentage of Participants Maintaining Deep Remission at Week 102(Week 102)
- Percentage of Participants Maintaining Endoscopic Healing at Week 102(Week 102)
- Percentage of Participants Maintaining Endoscopic Response at Week 102(Week 102)
- Percentage of Participants Maintaining Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 102(Week 102)
- Percentage of Participants With First Exacerbation of CD(After 26 Weeks up to Week 120)