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

Takeda

Status and phase: Enrolling; Phase 3

Conditions: Crohn's Disease

Treatments: Drug: Vedolizumab; Drug: Placebo; Drug: Upadacitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06227910

Vedolizumab-3043

2023-509391-42 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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-weeks Induction Phase:

• Induction Phase: Vedolizumab + Upadacitinib
• Induction Phase: Vedolizumab + Placebo

Participants who achieve a Crohn's disease activity index (CDAI) reduction of greater than or equal to (>=)70 points from baseline at Week 12 will enter the main study Maintenance Phase (40 weeks) 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.

Enrollment: 396 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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 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.
3. 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.
4. The participant has a history of recurrent or disseminated (including a single episode) herpes zoster, or disseminated (including a single episode) herpes simplex.
5. 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.
6. The participant has an ostomy or ileoanal pouch.
7. 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).
8. The participant has severe (Child-Pugh C) hepatic impairment.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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396 participants in 3 patient groups, including a placebo group

Double-blind Induction Phase: Vedolizumab + Upadacitinib

Experimental group

Description:

Participants will receive vedolizumab 300 mg intravenous (IV) infusion at Weeks 0, 2, 6 and 10 along with upadacitinib 45 mg, orally, once daily (QD) for 12 weeks.

Treatment:

Drug: Upadacitinib

Drug: Vedolizumab

Double-blind Induction Phase: Vedolizumab + Placebo

Placebo Comparator group

Description:

Participants will receive vedolizumab IV 300 mg infusion, at Weeks 0, 2, 6 and 10 along with upadacitinib matched placebo, orally, QD for 12 weeks.

Treatment:

Drug: Placebo

Drug: Vedolizumab

Main Study Maintenance Phase: Vedolizumab Monotherapy

Experimental group

Description:

Participants who achieve a CDAI reduction of \>=70 points from baseline at Week 12 will receive vedolizumab 300 mg IV infusion (monotherapy), every 8 weeks (Q8W) starting at Week 14 to 52. The Q8W vedolizumab monotherapy may be escalated to Q4W at the investigator's discretion.

Treatment:

Drug: Vedolizumab