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

Launched by TAKEDA · Sep 13, 2023

Keywords

ClinConnect Summary

This clinical trial is investigating the effects of a treatment called vedolizumab, given through an IV, combined with two other medications, adalimumab or ustekinumab, in adults with moderate to severe Crohn's Disease. The goal is to see how well this combination works compared to using vedolizumab alone after the combined treatment. The study is divided into two parts: in the first part, participants will receive the dual treatments, and in the second part, only vedolizumab will be given to those who show improvement after the first part. Participants will be followed for at least 26 weeks after their last treatment.

To be eligible for this trial, participants must have a confirmed diagnosis of Crohn's Disease for at least three months and experience moderate to severe symptoms. They should also have not responded well to at least one previous treatment for Crohn's Disease. The trial is open to adults aged 18 and older, regardless of gender. It’s important to note that individuals with certain medical conditions, such as active infections or previous serious reactions to similar treatments, may not qualify. Participants can expect regular check-ups and monitoring of their health throughout the study.

Gender

ALL

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 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 agents 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.