A Study of Vedolizumab Intravenous (IV) and Adalimumab or Vedolizumab and Ustekinumab in Adults With Crohn's Disease
Purpose
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.
Condition
- Crohn's Disease
Eligibility
- Eligible Ages
- Between 18 Years and 70 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
Part A: 1. Has a confirmed diagnosis of CD at least 3 months before screening, based on endoscopy results. 2. Has moderately to severely active CD at Screening, defined as an SES-CD >=6 (>=4 if isolated ileal disease). 3. 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: 1. Inadequate response after completing the full induction regimen; 2. Loss of response (recurrence of symptoms during scheduled maintenance dosing after prior clinical benefit); or 3. 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: 4. In the investigator's opinion, the participant exhibits a therapeutic benefit at Week 26.
Exclusion Criteria
- CDAI score > 450. 2. A current diagnosis of ulcerative colitis or indeterminate colitis. 3. Clinical evidence of an abdominal abscess. 4. Known fistula (other than perianal fistula) or phlegmon. 5. Known perianal fistula with abscess. 6. Ileostomy, colostomy, or severe, or symptomatic stenosis of the intestine. 7. Previous extensive bowel resection with 2 entire segments missing, of the following: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum. 8. Short bowel syndrome. 9. Any planned surgical intervention for CD, except for seton placement for perianal fistula without abscess. 10. History or evidence of adenomatous colonic polyps that have not been removed. 11. History or evidence of colonic mucosal dysplasia. 12. Intolerance or contraindication to ileocolonoscopy. 13. Any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency infection). 14. Active or latent tuberculosis (TB), regardless of treatment history. 15. 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. 16. A positive test for hepatitis C virus (HCV), as defined by a positive hepatitis C virus antibody (HCVAb) test and detectable HCV ribonucleic acid (RNA). 17. Received approved or investigational anti-integrin antibodies (i.e., vedolizumab, natalizumab, efalizumab, etrolizumab, abrilumab [AMG 181], anti- mucosal addressin cell adhesion molecule-1 [MAdCAM-1] antibodies, or rituximab) for the treatment of CD. 18. History of or symptoms of progressive multifocal leukoencephalopathy (PML) in the investigator's opinion. If a participant has symptoms consistent with PML, a PML checklist must be completed and submitted to the PML independent adjudication committee. If the PML IAC deems the participant to have PML, the participant is ineligible.
Study Design
- Phase
- Phase 4
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part A, Cohort 1: Vedolizumab + Adalimumab |
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. |
|
|
Experimental Part A, Cohort 2: Vedolizumab + Ustekinumab |
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. |
|
|
Experimental Part B: Vedolizumab Monotherapy |
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. |
|
Recruiting Locations
Dothan, Alabama 36301
Sun City, Arizona 85351
La Jolla, California 92037
Los Angeles, California 90048
Newport Beach, California 92663
Hamden, Connecticut 06518
Orlando, Florida 32803
Tampa, Florida 33615
Site Contact
813-515-5400
crespo@allianceclinicalresearch.com, luis@allianceclinicalresearch.com
Roswell, Georgia 30076
Chicago, Illinois 60637
Glenview, Illinois 60026
Gurnee, Illinois 60031
Kansas City, Kansas 66160
Topeka, Kansas 66606
Louisville, Kentucky 40202
Metairie, Louisiana 70006
New Orleans, Louisiana 70112
Ypsilanti, Michigan 48197
Kansas City, Missouri 64111
Liberty, Missouri 64068
St Louis, Missouri 63110
New York, New York 10016
Site Contact
646-754-1899
David.Hudesman@nyulangone.org; nathasha.melukkaran@nyulangone.org
Cincinnati, Ohio 45627
Columbus, Ohio 43202
Mentor, Ohio 44060
Westlake, Ohio 44145
Oklahoma City, Oklahoma 73114
Wexford, Pennsylvania 15090
Providence, Rhode Island 02094
Rapid City, South Dakota 57701
Cedar Park, Texas 78613
Dallas, Texas 75044
Houston, Texas 77030
Lubbock, Texas 79410
Mansfield, Texas 76063
Site Contact
817-877-0888
moustafa.youssef@dhat.com; Tamara.Marshall@GIAlliance.com; Olufemi.Oludotun@GiAlliance.com
San Antonio, Texas 78229
San Antonio, Texas 78229
Southlake, Texas 76092
Tyler, Texas 75701
Site Contact
903-630-6211
Aaron.duvall@iterativehealth.com; Rachel.hannah@iterativehealth.com
Webster, Texas 77598
Salt Lake City, Utah 84108
Tacoma, Washington 98405
More Details
- Status
- Recruiting
- Sponsor
- Takeda
Detailed Description
The drug being tested in this study is vedolizumab. Vedolizumab is being tested to treat people with moderate to severe Crohn's disease who have experienced inadequate response, loss of response or intolerance to either one prior interleukin [IL] antagonist, and no other biologic/small molecule (Group A); one IL antagonist and either one Janus kinase inhibitor (JAKi) or one TNFi (other than adalimumab) [Group B] (Cohort 1) or one prior tumor necrosis factor inhibitor [TNFi] and no other biologic/small molecule (Group C); one TNFi and either 1 JAKi or one IL antagonist (other than UST) (Group D) (Cohort 2). The study will look at the efficacy and safety of dual targeted therapy. The study will enroll approximately 100 participants. Participants will be assigned to one of the two treatment groups in Part A: - Part A, Cohort 1: Vedolizumab + Adalimumab - Part A, Cohort 2: Vedolizumab + Ustekinumab All participants who achieve therapeutic benefit in Part A will receive vedolizumab IV 300 mg monotherapy from Week 30 until Week 46 in Part B. Participants will be followed for a further 20-week safety follow-up period to Week 72 (or 26 weeks post-last dose of study drug). This multi-center trial will be conducted in the United States and Canada. The overall time to participate in this study is approximately 76 weeks.