Clinical trial NCT06045754: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Crohn's Disease
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2023-09-21
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main aim of this study is to learn about the effect of treatment with vedolizumab IV (vedolizumab) together with adalimumab or vedolizumab together with ustekinumab 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 (Cohort 1) or one prior tumor necrosis factor inhibitor \[TNFi\] (Cohort 2). The study will look at the efficacy and safety of dual targeted therapy.

The study will enroll approximately 150 patients. 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 clinical remission 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Percentage of Participants Achieving Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Week 26
timeFrame: Week 26
measure: Part B: Percentage of Participants in Clinical Remission Based on the CDAI at Week 52
timeFrame: Week 52
Secondary outcomes:
measure: Percentage of Participants Achieving Clinical Remission Based on the CDAI at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving 2-item Patient-reported Outcome Measure (PRO2) Remission at Weeks 12, 26, and 52
timeFrame: Weeks 12, 26 and 52
measure: Change in PRO2 Score from Week 26 to 52
timeFrame: Weeks 26 and 52
measure: Percentage of Participants with Stool Frequency Remission at Weeks 12, 26, and 52
timeFrame: Weeks 12, 26, and 52
measure: Percentage of Participants with Abdominal Pain Remission at Weeks 12, 26, and 52
timeFrame: Weeks 12, 26, and 52
measure: Percentage of Participants Achieving Endoscopic Remission Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) at Weeks 26 and 52
timeFrame: Weeks 26 and 52
measure: Percentage of Participants Achieving Endoscopic Remission Based on SES-CD at Both Weeks 26 and 52
timeFrame: Weeks 26 and 52
measure: Percentage of Participants Exhibiting an Endoscopic Response Based on SES-CD at Weeks 26 and 52
timeFrame: Weeks 26 and 52
measure: Percentage of Participants in Deep Remission Based on the CDAI and SES-CD at Weeks 26 and 52
timeFrame: Weeks 26 and 52
measure: Percentage of Participants in Deep Remission Based on the CDAI and SES-CD at Both Weeks 26 and 52
timeFrame: Weeks 26 and 52
measure: Percentage of Participants Exhibiting a Clinical Response Based on the CDAI at Weeks 12, 26, and 52
timeFrame: Weeks 12, 26, and 52
measure: Percentage of Participants Using Oral Corticosteroids at Baseline who have Discontinued Corticosteroids and are in Clinical Remission Based on the CDAI
timeFrame: Week 30 through Week 64
measure: Percentage of Participants Achieving Complete Endoscopic Healing Based on SES-CD at Weeks 26 and 52
timeFrame: Weeks 26 and 52
measure: Change in SES-CD from Baseline to Weeks 26 and 52
timeFrame: Baseline, Weeks 26 and 52
measure: Percentage of Participants with First CD Exacerbation After 26 Weeks
timeFrame: Week 26 through Week 52
measure: Change in FCP Concentrations from Baseline to Weeks 12, 26, 42, and 52
timeFrame: Baseline, Weeks 12, 26, 42, and 52
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialsits
state: Alabama
city: Sun City
country: United States
facility: GI Alliance Sun City
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego Health (UCSD)
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Newport Beach
country: United States
facility: Hoag Hospital Newport Beach
state: California
city: Hamden
country: United States
facility: Medical Research Center of Connecticut, LLC
state: Connecticut
city: Orlando
country: United States
facility: Endoscopic Research Inc
state: Florida
city: Tampa
country: United States
facility: Alliance Clinical Research of Tampa, LLC
state: Florida
city: Roswell
country: United States
facility: Gastroenterology Consultants, P.C.
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Glenview
country: United States
facility: GI Alliance - Illinois Gastroenterology Group - Glenview
state: Illinois
city: Gurnee
country: United States
facility: GI Alliance - Illinois Gastroenterology Group LLC - Gurnee
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Topeka
country: United States
facility: Cotton ONeil Clinical Research Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Metairie
country: United States
facility: GI Alliance
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Clinton Township
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Ypsilanti
country: United States
facility: Huron Gastroenterology Associates, P.C.
state: Michigan
city: Kansas City
country: United States
facility: Mid-America Gastro-Intestinal Consultants
state: Missouri
city: Liberty
country: United States
facility: BVL Clinical Research
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Ohio Gastroenterology group, Inc.
state: Ohio
city: Mentor
country: United States
facility: Great Lakes Gastroenterology Research, LLC
state: Ohio
city: Westlake
country: United States
facility: Gastro Intestinal Research Institute of Northern Ohio, LLC.
state: Ohio
city: Oklahoma City
country: United States
facility: Digestive Disease Specialists, Inc.
state: Oklahoma
city: Wexford
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Providence
country: United States
facility: University Gastroenterology
state: Rhode Island
city: Rapid City
country: United States
facility: Rapid City Medical Center, LLP
state: South Dakota
city: Cedar Park
country: United States
facility: Texas Digestive Disease Consultants Cedar Park
state: Texas
city: Dallas
country: United States
facility: GI Alliance - Digestive Health Associates of Texas
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Lubbock
country: United States
facility: Texas Digestive Disease Consultants Lubbock
state: Texas
city: Mansfield
country: United States
facility: GI Alliance - Mansfield
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Research of San Antonio, LLC
state: Texas
city: San Antonio
country: United States
facility: Southern Star Research Institute, LLC.
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants (TDDC), Southlake
state: Texas
city: Tyler
country: United States
facility: Tyler Research Institute, LLC
state: Texas
city: Webster
country: United States
facility: GI Alliance - Webster
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Bellevue
country: United States
facility: Washington Gastroenterology- GIA
state: Washington
city: Tacoma
country: United States
facility: Washington Gastroenterology- GIA
state: Washington
city: Edmonton
country: Canada
facility: Covenant Health
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Mississauga
country: Canada
facility: West GTA Endoscopy Inc.
state: Ontario
city: North Bay
country: Canada
facility: Viable Clinical Research - North Bay
state: Ontario
city: North York
country: Canada
facility: Toronto Immune and Digestive Health Institute Inc. (TIDHI)
state: Ontario
city: Oakville
country: Canada
facility: ABP Research Services Corp.
state: Ontario
city: Oshawa
country: Canada
facility: Taunton Surgical Centre
state: Ontario
city: Vaughan
country: Canada
facility: Toronto Digestive Disease Associates (TDDA) Specialty Research
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre Montreal General Hospital
state: Quebec
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: