Dual Targeted Therapy in Moderate to Severe Crohn's Disease

What is the Purpose of this Study?

The purpose of this study is to determine whether combining approved treatments (dual therapy) for Crohn’s disease is safe and improves patient outcomes. The treatment combinations referred to as “dual targeted therapy” are vedolizumab given by intravenous (IV) infusion plus adalimumab given by subcutaneous (SC- under the skin) injection, or vedolizumab given by IV infusion plus ustekinumab given by IV infusion for the first dose and SC injection for the rest of the doses. Treatment will consist of a 26-week dual therapy period and then, for some participants, a 26 week vedolizumab monotherapy (single therapy) treatment period. Study visits will consist of physical exams, laboratory tests, endoscopies, and completion of questionnaires. The combined use of vedolizumab, with either adalimumab or ustekinumab, as dual targeted therapy for the treatment of Crohn's disease is investigational.

Eligibility

Part A:
1. Has a confirmed diagnosis of CD at least 3 months before baseline, based on endoscopy results.
2. Has moderately to severely active CD at Screening, defined as a CDAI score ≥220 and a SES-CD ≥6 (≥4 if isolated ileal disease).

Inclusion Criteria:

Part A:
1. Has a confirmed diagnosis of CD at least 3 months before baseline, based on endoscopy results.
2. Has moderately to severely active CD at Screening, defined as a CDAI score ≥220 and a 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 primary nonresponse to ≥2 agents are not eligible. Participants with intolerance to 2 agents may be eligible at the investigator's discretion.
Part B:
4. Participant is in clinical remission at Week 26. Note: Participants exhibiting a clinical response (defined as a ≥ 100-point decrease in CDAI) at Week 26 may enter Part B at the investigator's discretion.

Exclusion Criteria:

1. A current diagnosis of ulcerative colitis or indeterminate colitis.
2. Clinical evidence of a current abdominal abscess or a history of prior abdominal abscess.
3. Known fistula (other than perianal fistula) or phlegmon.
4. Known perianal fistula with abscess.
5. Ileostomy, colostomy, or severe, or symptomatic stenosis of the intestine.
6. Previous extensive colon resection with ≥2 colonic segments remaining, performed ≥ 6 months prior to screening.
7. Short bowel syndrome.
8. Any planned surgical intervention for CD, except for seton placement for perianal fistula without abscess.
9. History or evidence of adenomatous colonic polyps that have not been removed.
10. History or evidence of colonic mucosal dysplasia.
11. Intolerance or contraindication to ileocolonoscopy.
12. Any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus \[HIV\] infection).
13. Active or latent tuberculosis (TB), regardless of treatment history.
14. 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.
15. 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).
16. Primary nonresponse to ≥2 IL antagonists (Cohort 1) or ≥2 TNF antagonists (Cohort 2) for the treatment of CD.
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).
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 (IAC). If the PML IAC deems the participant to have PML, the participant is ineligible.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

An Open-Label, Phase 4 Study to Evaluate the Efficacy and Safety of Dual Targeted Therapy with Vedolizumab Intravenous and Adalimumab Subcutaneous or Vedolizumab IV and Ustekinumab IV/SC in Moderate to Severe Crohn's Disease

Study Details

Disease Type/Condition

Other

Principal Investigator

Yarur, Andres

Co-Investigators

Andrea Banty, Gil Melmed, Susie Lee, Teddy Solomon

Age Group

Adult

Phase

IRB Number

STUDY00002820

ClinicalTrials.gov ID

NCT06045754

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org