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

Takeda

Status and phase: Enrolling; Phase 4

Conditions: Crohn's Disease

Treatments: Drug: Vedolizumab; Drug: Adalimumab; Drug: Ustekinumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06045754

EXPLORER 2.0 (Other Identifier)

Vedolizumab-4051

MACS-2022-120102 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 3 patient groups

Part A, Cohort 1: Vedolizumab + Adalimumab

Experimental group

Description:

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.

Treatment:

Drug: Adalimumab

Drug: Vedolizumab

Part A, Cohort 2: Vedolizumab + Ustekinumab

Experimental group

Description:

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.

Treatment:

Drug: Ustekinumab

Drug: Ustekinumab

Drug: Vedolizumab

Part B: Vedolizumab Monotherapy

Experimental group

Description:

Participants who achieve clinical remission 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.

Treatment:

Drug: Vedolizumab