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

Phase 4

Recruiting

• Conditions: Crohn's Disease
• Interventions: Drug: Vedolizumab; Drug: Adalimumab; Drug: Ustekinumab

• Registration Number: NCT06045754
• Lead Sponsor: Takeda

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 (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.

Study Timeline

• Study First Submitted: 2023-09-13
• Study First Submitted QC: 2023-09-13
• Study First Posted: 2023-09-21
• Study Start: 2024-04-18
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-04
• Last Update Posted: 2025-09-05
• Primary Completion: 2027-06-28
• Study Completion: 2027-06-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A, Cohort 1: Vedolizumab + Adalimumab	Vedolizumab	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.
Part A, Cohort 1: Vedolizumab + Adalimumab	Adalimumab	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.
Part A, Cohort 2: Vedolizumab + Ustekinumab	Vedolizumab	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.
Part A, Cohort 2: Vedolizumab + Ustekinumab	Ustekinumab	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.
Part B: Vedolizumab Monotherapy	Vedolizumab	Participants who achieve therapeutic benefit 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.

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures

Name	Time	Method
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	At Weeks 12, 26, and 52	Clinical remission is defined as a CDAI score of \<150 points. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit and body weight. CDAI consists of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity. Percentage of participants in clinical remission based on CDAI at either Week 12, Week 26, or Week 52 will be reported in this outcome measure.
Percentage of Participants in Clinical Remission at Both Week 26 and Week 52	At Weeks 26 and 52	Clinical remission is defined as a CDAI score of ≤150 points. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit and body weight. CDAI consists of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity. Percentage of participants in clinical remission at both Week 26 and Week 52 will be reported in this outcome measure.
Percentage of Participants in 2-item Patient-reported Outcome Measure (PRO2) Remission at Weeks 12, 26, and 52	At Weeks 12, 26 and 52	Clinical remission based on PRO2 is defined as PRO2 score \<=8 from baseline. The PRO2 is comprised of the stool frequency and abdominal pain components of the CDAI. The PRO-2 score is the sum of the abdominal pain and stool frequency subscores of the CDAI score. The average daily number of liquid or very soft stools and abdominal pain score (with 0 indicating no pain and 3 indicating severe pain) are weighted according to the CDAI multiplication factors (2 for stool frequency and 5 for abdominal pain). A higher score indicates more frequent stools and more severe abdominal pain.
Change in PRO2 Score from Week 26 to 52	From Week 26 up to Week 52	The PRO2 is comprised of the stool frequency and abdominal pain components of the CDAI. The PRO-2 score is the sum of the abdominal pain and stool frequency subscores of the CDAI score. The average daily number of liquid or very soft stools and abdominal pain score (with 0 indicating no pain and 3 indicating severe pain) are weighted according to the CDAI multiplication factors (2 for stool frequency and 5 for abdominal pain). A higher score indicates more frequent stools and more severe abdominal pain.
Percentage of Participants in Stool Frequency Remission	At Weeks 12, 26, and 52	Stool frequency remission is defined as an average daily stool frequency of \<=3 that is not worse than baseline.
Percentage of Participants in Abdominal Pain Remission	At Weeks 12, 26, and 52	Abdominal pain remission is defined as an abdominal pain score of \<=1 that is not worse than baseline.
Percentage of Participants in Endoscopic Remission (SES-CD 0-2) at Week 26 and Week 52	At Weeks 26 and 52	Endoscopic remission is defined as SES-CD score from 0-2. 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 sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease. Percentage of participants achieving endoscopic remission based on SES-CD at either Week 26 or Week 52 will be reported in this outcome measure.
Percentage of Participants in Endoscopic Remission at Both Week 26 and Week 52	At Weeks 26 and 52	Endoscopic remission as per SES-CD is defined as SES-CD score from 0-2. 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 sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease. Percentage of participants achieving endoscopic remission based on SES-CD at both Weeks 26 and 52 will be reported in this outcome measure.
Percentage of Participants in Deep Remission Based on the CDAI and SES-CD at Week 26 and Week 52	At Weeks 26 and 52	Deep remission:CDAI \<150 points and SES-CD 0-2. CDAI assesses CD per clinical signs such as number of liquid/soft stools,abdominal pain,general wellbeing,extra-intestinal manifestations of CD, antidiarrheal use,presence of abdominal mass, hematocrit and body weight. It has 8 factors each summed after adjustment with weighting factor; total score:0 to 600 points, higher scores=more severity. SES-CD evaluates 4 endoscopic variables(ulcer size, percentage of ulcerated surface area, percentage of affected surface area, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0=none or not severe to 3=most severe case; sum of the scores range from 0 to 15, except for narrowing. Presence of narrowing ranges from 0 to 11. Overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables. Higher scores=more severe disease. Participants achieving deep remission at either Week 26 or 52 will be assessed in this outcome measure.
Percentage of Participants in Deep Remission at Both Week 26 and Week 52	At Weeks 26 and Week 52	Deep remission: CDAI \<150 points and SES-CD 0-2. CDAI assesses CD per clinical signs such as number of liquid/soft stools,abdominal pain,general wellbeing,extra-intestinal manifestations of CD, antidiarrheal use,presence of abdominal mass, hematocrit and body weight. It has 8 factors each summed after adjustment with weighting factor; total score:0 to 600 points, higher scores=more severity. SES-CD evaluates 4 endoscopic variables(ulcer size, percentage of ulcerated surface area, percentage of affected surface area, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0=none or not severe to 3=most severe case; sum of the scores range from 0 to 15, except for narrowing. Presence of narrowing ranges from 0 to 11. Overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables. Higher scores=more severe disease. Participants achieving deep remission at both Weeks 26 and 52 will be assessed in this outcome measure.
Percentage of Participants With a Clinical Response (>=100-point Decrease from Baseline in CDAI Score)	At Weeks 12, 26, and 52	Clinical response is defined as \>=100-point decrease from Baseline in CDAI score. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit and body weight. CDAI consist of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity.
Percentage of Participants With Complete Endoscopic Healing	At Weeks 26 and 52	Complete endoscopic healing is defined as SES-CD score ≤4 with a ≥2-point decrease from baseline and no individual subscore \>1. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is the most severe case, with the sum of the 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.
Percentage of Participants Using Oral Corticosteroids at Baseline who are in Clinical Remission Based on CDAI Score and had Discontinued Corticosteroids	From Week 26 to Week 52	Percentage of participants using oral corticosteroids at Baseline who are in clinical remission based on the CDAI score and had discontinued corticosteroids within \>=30 days of Week 26 and within \>= 90 days of Week 52. Clinical remission is defined as a CDAI score of ≤150 points. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit and body weight. CDAI consist of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity.
Change in SES-CD from Baseline to Week 26 and Week 52	Baseline, Week 26 and Week 52	SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is the most severe case, with the sum of the 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.
Change in FCP Concentrations from Baseline to Week 12, Week 26, Week 42, and Week 52	Baseline, Weeks 12, 26, 42, and 52
Percentage of Participants with First CD Exacerbation After 26 Weeks	From Week 26 through Week 52	CD exacerbation is defined as a \>70-point increase in CDAI from the prior visit on 2 occasions separated by a 2-week interval, and either CRP above normal or fecal calprotectin \[FCP\] \>250 micrograms per gram (μg/g). CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit and body weight. CDAI consist of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity.

Trial Locations

Locations (53)

Digestive Health Specialsits; 🇺🇸 Dothan, Alabama, United States

GI Alliance Sun City; 🇺🇸 Sun City, Arizona, United States

University of California San Diego Health (UCSD); 🇺🇸 La Jolla, California, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Hoag Hospital Newport Beach; 🇺🇸 Newport Beach, California, United States

Medical Research Center of Connecticut, LLC; 🇺🇸 Hamden, Connecticut, United States

Clinical Research of Osceola; 🇺🇸 Kissimmee, Florida, United States

Endoscopic Research Inc; 🇺🇸 Orlando, Florida, United States

Alliance Clinical Research of Tampa, LLC; 🇺🇸 Tampa, Florida, United States

Gastroenterology Consultants, P.C.; 🇺🇸 Roswell, Georgia, United States

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