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A Study of Vedolizumab Intravenous (IV) and Adalimumab or Vedolizumab and Ustekinumab in Adults With Crohn's Disease

NCT06045754 · Takeda
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Official title
An Open-Label, Phase 4 Study to Evaluate the Efficacy and Safety of Dual Targeted Therapy With Vedolizumab Intravenous (IV) and Adalimumab Subcutaneous (SC) or Vedolizumab IV and Ustekinumab IV/SC in Moderate to Severe Crohn's Disease (CD)
About this study
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.
Eligibility criteria
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: 1. 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
Enrollment target: 100 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-04-18
Estimated completion: 2027-06-28
Last updated: 2026-03-18
Interventions
Drug: VedolizumabDrug: AdalimumabDrug: UstekinumabDrug: Ustekinumab
Primary outcomes
  • Part A: Percentage of Participants With an Endoscopic Response Based on the Simple Endoscopic Score for (SES-CD) at Week 26 (At Week 26)
  • Part B: Percentage of Participants With an Endoscopic Response Based on the SES-CD at Week 52 (At Week 52)
Sponsor
Takeda · industry
Contacts & investigators
ContactTakeda Contact · contact · medinfoUS@takeda.com · +1-877-825-3327
InvestigatorStudy Director · study_director, Takeda
All locations (54)
Digestive Health SpecialsitsRecruiting
Dothan, Alabama, United States
GI Alliance Sun CityRecruiting
Sun City, Arizona, United States
University of California San Diego Health (UCSD)Recruiting
La Jolla, California, United States
Cedars-Sinai Medical CenterRecruiting
Los Angeles, California, United States
Hoag Hospital Newport BeachRecruiting
Newport Beach, California, United States
Medical Research Center of Connecticut, LLCRecruiting
Hamden, Connecticut, United States
Clinical Research of OsceolaRecruiting
Kissimmee, Florida, United States
Endoscopic Research IncRecruiting
Orlando, Florida, United States
University of South FloridaNot Yet Recruiting
Tampa, Florida, United States
Alliance Clinical Research of Tampa, LLCRecruiting
Tampa, Florida, United States
Gastroenterology Consultants, P.C.Recruiting
Roswell, Georgia, United States
University of Chicago MedicineRecruiting
Chicago, Illinois, United States
GI Alliance - Illinois Gastroenterology Group - GlenviewRecruiting
Glenview, Illinois, United States
GI Alliance - Illinois Gastroenterology Group LLC - GurneeRecruiting
Gurnee, Illinois, United States
University of Kansas Medical CenterRecruiting
Kansas City, Kansas, United States
Cotton ONeil Clinical Research CenterRecruiting
Topeka, Kansas, United States
University of LouisvilleRecruiting
Louisville, Kentucky, United States
GI AllianceRecruiting
Metairie, Louisiana, United States
Tulane UniversityRecruiting
New Orleans, Louisiana, United States
Huron Gastroenterology Associates, P.C.Recruiting
Ypsilanti, Michigan, United States
Mid-America Gastro-Intestinal ConsultantsRecruiting
Kansas City, Missouri, United States
BVL Clinical ResearchRecruiting
Liberty, Missouri, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
NYU Langone HealthRecruiting
New York, New York, United States
University of CincinnatiRecruiting
Cincinnati, Ohio, United States
Ohio Gastroenterology group, Inc.Recruiting
Columbus, Ohio, United States
Great Lakes Gastroenterology Research, LLCRecruiting
Mentor, Ohio, United States
Gastro Intestinal Research Institute of Northern Ohio, LLC.Recruiting
Westlake, Ohio, United States
Digestive Disease Specialists, Inc.Recruiting
Oklahoma City, Oklahoma, United States
Allegheny Health NetworkRecruiting
Wexford, Pennsylvania, United States
University GastroenterologyRecruiting
Providence, Rhode Island, United States
Rapid City Medical Center, LLPRecruiting
Rapid City, South Dakota, United States
Texas Digestive Disease Consultants Cedar ParkRecruiting
Cedar Park, Texas, United States
GI Alliance - Digestive Health Associates of TexasRecruiting
Dallas, Texas, United States
The University of Texas Health Science Center at HoustonRecruiting
Houston, Texas, United States
Texas Digestive Disease Consultants LubbockRecruiting
Lubbock, Texas, United States
GI Alliance - MansfieldRecruiting
Mansfield, Texas, United States
Gastroenterology Research of San Antonio, LLCRecruiting
San Antonio, Texas, United States
Southern Star Research Institute, LLC.Recruiting
San Antonio, Texas, United States
Texas Digestive Disease Consultants (TDDC), SouthlakeRecruiting
Southlake, Texas, United States
Tyler Research Institute, LLCRecruiting
Tyler, Texas, United States
GI Alliance - WebsterRecruiting
Webster, Texas, United States
University of Utah HealthRecruiting
Salt Lake City, Utah, United States
Washington Gastroenterology- GIAWithdrawn
Bellevue, Washington, United States
Washington Gastroenterology- GIARecruiting
Tacoma, Washington, United States
Covenant HealthRecruiting
Edmonton, Alberta, Canada
London Health Sciences CentreRecruiting
London, Ontario, Canada
West GTA Endoscopy Inc.Recruiting
Mississauga, Ontario, Canada
Viable Clinical Research - North BayRecruiting
North Bay, Ontario, Canada
Toronto Immune and Digestive Health Institute Inc. (TIDHI)Recruiting
North York, Ontario, Canada
ABP Research Services Corp.Recruiting
Oakville, Ontario, Canada
Taunton Surgical CentreWithdrawn
Oshawa, Ontario, Canada
Toronto Digestive Disease Associates (TDDA) Inc.Recruiting
Vaughan, Ontario, Canada
The Research Institute of the McGill University Health CentreRecruiting
Montreal, Quebec, Canada
A Study of Vedolizumab Intravenous (IV) and Adalimumab or Vedolizumab and Ustekinumab in Adults With Crohn's Disease · TrialPath