A Study of Vedolizumab With and Without Upadacitinib in Adults With Crohn's Disease

Crohn's Disease Clinical Trial

— VICTRIVA  

Official title:

A Randomized, Double-Blind, Placebo-Controlled Phase 3b Study to Evaluate the Short- and Long-Term Efficacy and Safety of Dual Targeted Therapy With Intravenous Vedolizumab and Oral Upadacitinib Compared With Intravenous Vedolizumab Monotherapy for the Treatment of Adult Participants With Moderately to Severely Active Crohn's Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06227910
• Other study ID #: Vedolizumab-3043
• Secondary ID: 2023-509391-42
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 22, 2024
• Est. completion date: August 1, 2028

Study information

• Verified date: February 2024
• Source: Takeda
• Contact: Takeda Contact
• Phone: +1-877-825-3327
• Email: medinfoUS[@]takeda.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main aim of this study is to learn whether vedolizumab and upadacitinib given together (also called dual targeted therapy or DTT) reduces bowel inflammation and ulcers in the bowel compared to vedolizumab only (also called monotherapy) in adults with moderately or severely active Crohn's Disease (CD) after 12 weeks of treatment. Other aims are to learn how safe and effective DTT is compared to monotherapy for these participants. All participants will receive DTT (either vedolizumab and upadacitinib or vedolizumab and placebo) for 12 weeks. Participants responding to the treatment will then receive vedolizumab only (monotherapy) for an additional 40 weeks. During the study, participants will visit their study clinic 15 times.

Description:

The drug being tested in this study is vedolizumab. Vedolizumab is being tested to treat people with moderately to severely active CD. The study will look at the efficacy and safety of vedolizumab with and without upadacitinib. The study will enroll approximately 396 patients. Participants will be assigned in a 1:1 ratio to one of the two treatment groups in the 12-week Induction Period: - Induction Period: Vedolizumab + Upadacitinib - Induction Period: Vedolizumab + Placebo Participants who achieve a Crohn's disease activity index (CDAI) reduction of ≥70 points from baseline at Week 12 will progress into the 40-week Maintenance Period of the study to receive vedolizumab monotherapy. Participants will be followed for a further 18-week safety follow-up period up to Week 70. This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 70 weeks.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 396
• Est. completion date: August 1, 2028
• Est. primary completion date: June 8, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. The participant has a diagnosis of CD established at least 3 months before screening by clinical and endoscopic evidence and corroborated by a histopathology report.

2. The participant has a confirmed diagnosis of moderately to severely active CD as assessed by CDAI of 220-450.

3. The participant has evidence of mucosal inflammation based on the SES-CD: SES-CD score (excluding the presence of narrowing component) of =6 (or =4 for participants with isolated ileal disease), as confirmed by a central reader.

4. The participant has demonstrated an inadequate response to, loss of response to, or intolerance to corticosteroids, immunomodulators, or biologic therapy.

Exclusion Criteria:

1. The participant has a current diagnosis of ulcerative colitis or indeterminate colitis.

2. The participant has previously failed >2 classes of either biological or small molecule therapy for CD.

3. The participant has infection(s) requiring treatment with IV anti-infectives within 30 days prior to baseline or oral/intramuscular anti-infectives within 14 days prior to baseline.

4. The participant has evidence of an active infection during the screening period, or clinically significant infection within 30 days prior to screening, or ongoing chronic infection.

5. The participant has a history of recurrent or disseminated (including a single episode) herpes zoster, or disseminated (including a single episode) herpes simplex.

6. The participant has any of the following ongoing known complications of CD: abscess (abdominal or peri-anal); symptomatic bowel strictures; 2 entire missing segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum; fulminant colitis; toxic megacolon; or any other manifestation that might require surgery while enrolled in the study.

7. The participant has an ostomy or ileoanal pouch.

8. The participant has severe renal impairment, defined as an estimated glomerular filtration rate of <30 milliliters per minute per 1.73 square meters (mL/min/1.73 m^2).

9. The participant has severe (Child-Pugh C) hepatic impairment.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• Vedolizumab
Vedolizumab IV infusion.
• Upadacitinib
Upadacitinib over-encapsulated tablets.
• Placebo
Upadacitinib matched placebo capsules.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Clinical Remission Based on the CDAI at Week 12	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.	Week 12
Primary	Percentage of Participants Exhibiting an Endoscopic Response Based on Simple Endoscopic Score for CD (SES-CD) at Week 12	Endoscopic response as per SES-CD is defined as SES-CD reduction by =50% from Baseline as scored by a central reviewer. 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.	Week 12
Secondary	Percentage of Participants Achieving 2-item Patient-reported Outcome Measure (PRO2) Based Clinical Remission at Week 12	Clinical remission based on PRO2 is defined as 7-day average of very soft or liquid stool frequency (SF) =2.8, 7-day average of abdominal pain (AP) score =1.0, and neither worse than baseline. The PRO2 is comprised of the stool frequency and abdominal pain components of the CDAI.	Week 12
Secondary	Percentage of Participants Achieving Endoscopic Remission Based on SES-CD at Week 12	Endoscopic remission as per SES-CD is defined as SES-CD score of =4 with no mucosal ulceration in the colon or ileum as assessed by centrally read video ileocolonoscopy. 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.	Week 12
Secondary	Percentage of Participants Exhibiting Corticosteroid-free Clinical Remission in Participants who Were Taking Corticosteroids at Baseline Based on the CDAI at Week 12	Percentage of participants using oral corticosteroids at Baseline who have discontinued corticosteroids and are in clinical remission per CDAI at Week 12 will be reported. 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.	Week 12
Secondary	Percentage of Participants Exhibiting a Clinical Response Based on the CDAI at Week 12	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.	Week 12
Secondary	Percentage of Participants Achieving Clinical Remission Based on the CDAI at 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 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.	Week 52
Secondary	Percentage of Participants Exhibiting an Endoscopic Response Based on SES-CD at Week 52	Endoscopic response as per SES-CD is defined as SES-CD reduction by =50% from Baseline as scored by a central reviewer. 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.	Week 52
Secondary	Percentage of Participants Achieving 2-item PRO2 Based Clinical Remission at Week 52	Clinical remission based on PRO2 is defined as 7-day average of very soft or liquid stool frequency (SF) =2.8, 7-day average of abdominal pain (AP) score =1.0, and neither worse than baseline. The PRO2 is comprised of the stool frequency and abdominal pain components of the CDAI.	Week 52
Secondary	Percentage of Participants Achieving Endoscopic Remission Based on SES-CD at Week 52	Endoscopic remission as per SES-CD is defined as SES-CD score of =4 with no mucosal ulceration in the colon or ileum as assessed by centrally read video ileocolonoscopy. 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.	Week 52
Secondary	Percentage of Participants Exhibiting Corticosteroid-free Clinical Remission in Participants who Were Taking Corticosteroids at Baseline Based on the CDAI at Week 52	Percentage of participants using oral corticosteroids at Baseline who have discontinued corticosteroids and are in clinical remission at Week 52 per CDAI will be reported. 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.	Week 52
Secondary	Percentage of Participants Exhibiting a Clinical Response Based on the CDAI at Week 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.	Week 52

External Links

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