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

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)

Overview

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.

Detailed 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.

Interventions

• Drug Vedolizumab
  Vedolizumab intravenous infusion.
• Drug Adalimumab
  Adalimumab subcutaneous injection.
• Drug Ustekinumab
  Ustekinumab intravenous infusion.
• Drug Ustekinumab
  Ustekinumab subcutaneous injection.

Primary outcome measures

• Part A: Percentage of Participants With an Endoscopic Response Based on the Simple Endoscopic Score for (SES-CD) at Week 26 [Time frame: At Week 26]
• Part B: Percentage of Participants With an Endoscopic Response Based on the SES-CD at Week 52 [Time frame: At Week 52]

Secondary outcome measures (12)

• Percentage of Participants in Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) (CDAI <150) at Week 12, Week 26, and Week 52 [Time frame: At Weeks 12, 26, and 52]
• Percentage of Participants in Clinical Remission at Both Week 26 and Week 52 [Time frame: At Weeks 26 and 52]
• Percentage of Participants in 2-item Patient-reported Outcome Measure (PRO2) Remission at Weeks 12, 26, and 52 [Time frame: At Weeks 12, 26 and 52]
• Change in PRO2 Score from Week 26 to 52 [Time frame: From Week 26 up to Week 52]
• Percentage of Participants in Stool Frequency Remission [Time frame: At Weeks 12, 26, and 52]
• Percentage of Participants in Abdominal Pain Remission [Time frame: At Weeks 12, 26, and 52]
• Percentage of Participants in Endoscopic Remission (SES-CD 0-2) at Week 26 and Week 52 [Time frame: At Weeks 26 and 52]
• Percentage of Participants in Endoscopic Remission at Both Week 26 and Week 52 [Time frame: At Weeks 26 and 52]
• Percentage of Participants in Deep Remission Based on the CDAI and SES-CD at Week 26 and Week 52 [Time frame: At Weeks 26 and 52]
• Percentage of Participants in Deep Remission at Both Week 26 and Week 52 [Time frame: At Weeks 26 and Week 52]
• Percentage of Participants With a Clinical Response (>=100-point Decrease from Baseline in CDAI Score) [Time frame: At Weeks 12, 26, and 52]
• Percentage of Participants With Complete Endoscopic Healing [Time frame: At Weeks 26 and 52]

Eligibility criteria

Inclusion criteria

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 criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 44 centers

• Digestive Health Specialsits — Dothan
• GI Alliance Sun City — Sun City
• University of California San Diego Health (UCSD) — La Jolla
• Cedars-Sinai Medical Center — Los Angeles
• Hoag Hospital Newport Beach — Newport Beach
• Medical Research Center of Connecticut, LLC — Hamden
• Clinical Research of Osceola — Kissimmee
• Endoscopic Research Inc — Orlando
• … and 36 more centers

Canada · 9 centers

• Covenant Health — Edmonton
• London Health Sciences Centre — London
• West GTA Endoscopy Inc. — Mississauga
• Viable Clinical Research - North Bay — North Bay
• Toronto Immune and Digestive Health Institute Inc. (TIDHI) — North York
• ABP Research Services Corp. — Oakville
• Taunton Surgical Centre — Oshawa
• Toronto Digestive Disease Associates (TDDA) Inc. — Vaughan
• … and 1 more center

Identifiers

NCT: NCT06045754 · Vedolizumab-4051 · MACS-2022-120102 · EXPLORER 2.0

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗