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

Vedolizumab-3043

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.

2024-07-22

2027-06-08

2028-08-01

Not yet recruiting

Early phase I

396

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.

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2024-02-08