A Study of Vedolizumab Intravenous (IV) and Adalimumab or Vedolizumab and Ustekinumab in Adults With Crohn's Disease
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)
Takeda
100 participants
Apr 18, 2024
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria10
- Part A:
- Has a confirmed diagnosis of CD at least 3 months before screening, based on endoscopy results.
- Has moderately to severely active CD at Screening, defined as an SES-CD \>=6 (\>=4 if isolated ileal disease).
- 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:
- Inadequate response after completing the full induction regimen;
- Loss of response (recurrence of symptoms during scheduled maintenance dosing after prior clinical benefit); or
- 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:
- In the investigator's opinion, the participant exhibits a therapeutic benefit at Week 26.
Exclusion Criteria18
- CDAI score \> 450.
- A current diagnosis of ulcerative colitis or indeterminate colitis.
- Clinical evidence of an abdominal abscess.
- Known fistula (other than perianal fistula) or phlegmon.
- Known perianal fistula with abscess.
- Ileostomy, colostomy, or severe, or symptomatic stenosis of the intestine.
- Previous extensive bowel resection with 2 entire segments missing, of the following: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum.
- Short bowel syndrome.
- Any planned surgical intervention for CD, except for seton placement for perianal fistula without abscess.
- History or evidence of adenomatous colonic polyps that have not been removed.
- History or evidence of colonic mucosal dysplasia.
- Intolerance or contraindication to ileocolonoscopy.
- Any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency infection).
- Active or latent tuberculosis (TB), regardless of treatment history.
- 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.
- 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).
- 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.
- 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.
Interventions
Vedolizumab intravenous infusion.
Adalimumab subcutaneous injection.
Ustekinumab intravenous infusion.
Ustekinumab subcutaneous injection.
Locations(54)
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NCT06045754