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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
70 Years
Healthy volunteers
No
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 an 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 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:
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.
Primary outcome measure(s)
Part A: Percentage of Participants With an Endoscopic Response Based on the Simple Endoscopic Score for (SES-CD) at Week 26 — At Week 26 Endoscopic response is defined by a \>=50 percent (%) reduction from baseline in the SES-CD. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of surface area (SA) that is ulcerated, percentage of SA affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is most severe case, with sum of scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease.
Part B: Percentage of Participants With an Endoscopic Response Based on the SES-CD at Week 52 — At Week 52 Endoscopic response is defined by a \>=50 reduction from baseline in the SES-CD. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of surface area (SA) that is ulcerated, percentage of SA affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is most severe case, with sum of scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease.
Trial sites (48)
Facility
City
Region
Status
Digestive Health Specialsits
Dothan
Alabama
Recruiting
GI Alliance Sun City
Sun City
Arizona
Recruiting
University of California San Diego Health (UCSD)
La Jolla
California
Recruiting
Cedars-Sinai Medical Center
Los Angeles
California
Recruiting
Hoag Hospital Newport Beach
Newport Beach
California
Recruiting
Medical Research Center of Connecticut, LLC
Hamden
Connecticut
Recruiting
Clinical Research of Osceola
Kissimmee
Florida
Recruiting
Endoscopic Research Inc
Orlando
Florida
Recruiting
Alliance Clinical Research of Tampa, LLC
Tampa
Florida
Recruiting
Gastroenterology Consultants, P.C.
Roswell
Georgia
Recruiting
University of Chicago Medicine
Chicago
Illinois
Recruiting
University of Kansas Medical Center
Kansas City
Kansas
Recruiting
Cotton ONeil Clinical Research Center
Topeka
Kansas
Recruiting
University of Louisville
Louisville
Kentucky
Recruiting
GI Alliance
Metairie
Louisiana
Recruiting
Tulane University
New Orleans
Louisiana
Recruiting
Huron Gastroenterology Associates, P.C.
Ypsilanti
Michigan
Recruiting
Mid-America Gastro-Intestinal Consultants
Kansas City
Missouri
Recruiting
BVL Clinical Research
Liberty
Missouri
Recruiting
Washington University School of Medicine
St Louis
Missouri
Recruiting
NYU Langone Health
New York
New York
Recruiting
University of Cincinnati
Cincinnati
Ohio
Recruiting
Ohio Gastroenterology group, Inc.
Columbus
Ohio
Recruiting
Great Lakes Gastroenterology Research, LLC
Mentor
Ohio
Recruiting
Gastro Intestinal Research Institute of Northern Ohio, LLC.
Westlake
Ohio
Recruiting
Digestive Disease Specialists, Inc.
Oklahoma City
Oklahoma
Recruiting
Allegheny Health Network
Wexford
Pennsylvania
Recruiting
University Gastroenterology
Providence
Rhode Island
Recruiting
Sanford Health Research
Rapid City
South Dakota
Recruiting
Texas Digestive Disease Consultants Cedar Park
Cedar Park
Texas
Recruiting
GI Alliance - Digestive Health Associates of Texas
Dallas
Texas
Recruiting
The University of Texas Health Science Center at Houston
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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