A Phase 4 Open-Label Study to Evaluate Vedolizumab IV Dose Optimization on Treatment Outcomes In Nonresponders With Moderately to Severely Active Ulcerative Colitis (ENTERPRET)

  • STATUS
    Recruiting
  • sponsor
    Takeda
Updated on 25 March 2021

Summary

A Phase 4 Open-Label Study to Evaluate Vedolizumab IV Dose Optimization on Treatment Outcomes In Nonresponders With Moderately to Severely Active Ulcerative Colitis (ENTERPRET)

Description

The drug being tested in this study is called Vedolizumab. Vedolizumab will be administered as an IV infusion. It is being tested in this study with new doses. This study will investigate the efficacy and safety of dose optimization of vedolizumab IV, compared with standard dosing of vedolizumab IV, over a 30-week treatment period.

The study will enroll approximately 200 moderately to severely active patients with ulcerative colitis in order to randomize 100 nonresponder patients. Participants will receive induction therapy of vedolizumab IV 300 mg on Day 1 and Week 2 (Lead-in Period). At Week 5, serum vedolizumab concentration will be measured. At Week 6, participants will be assessed for clinical response based on partial Mayo score.

Results of both Week 5 vedolizumab concentration and Week 6 clinical response will determine the treatment pathway. Those who are non-responders based on partial Mayo score at Week 6 and who are assessed as having high vedolizumab clearance, based on a predefined Week 5 serum vedolizumab concentration threshold (>50 µg/mL) will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:

  1. Vedolizumab IV Standard Treatment
  2. Vedolizumab IV Dose Optimized

All randomized participants will receive vedolizumab IV either 300 mg or 600 mg every 4 or 8 weeks.

This multi-center trial will be conducted in United States of America and Canada. The overall time to participate in this study is 56 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone, 6 months after last dose of study drug for a long term follow-up safety survey.

Details
Condition Ulcerative Colitis
Clinical Study IdentifierTX153812
SponsorTakeda
Last Modified on25 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Has a diagnosis of ulcerative colitis (UC) established at least 1 month prior to Screening by clinical and endoscopic evidence and corroborated by a histopathology report
Has moderately to severely active UC as determined by a complete Mayo score of 6 to 12 with an endoscopic subscore ≥2 within 28 days prior to enrollment
Has evidence of UC proximal to the rectum (=15 cm of involved colon) prior to start of vedolizumab intravenous (IV) dosing
Has been determined to be suitable for vedolizumab IV for routine management of UC by their physician
The participant with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance (may be performed during screening)
Has had an inadequate response with, lost response to, or intolerance of at least 1 of the following agents: immunomodulators, corticosteroids, or TNF-a antagonists. Participants who are naive to tumor necrosis factor- alfa (TNF-a) antagonist therapy or who have previously failed TNF-a antagonist therapy (including primary and secondary non-responders or intolerant) may be included
Week 6 Randomized Treatment Period Inclusion Criteria
Following Lead-in Period, the participant is assessed as having high vedolizumab drug clearance based on a predefined Week 5 serum vedolizumab concentration threshold (<50 µg/mL). Following Lead-in Period, the participant is a non-responder based on partial Mayo score at Week 6

Exclusion Criteria

Has clinical evidence of abdominal abscess or toxic megacolon at the Screening Visit
Has had an extensive colonic resection, subtotal or total colectomy
Has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
Has a diagnosis of Crohn's colitis or indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis
Has received any of the following for the treatment of underlying disease within 30 days of screening
Non-biologic therapies (eg. cyclosporine, tacrolimus, thalidomide)
An approved non-biologic therapy in an investigational protocol
Has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half lives prior to screening (whichever is longer)
Has previously received natalizumab, efalizumab, etrolizumab, AMG-181, MAdCAM-1 antibodies or rituximab
Has previously received vedolizumab IV
The participant currently requires or is anticipated to require surgical intervention for UC during the study
Has history or evidence of adenomatous colonic polyps that have not been removed, or colonic mucosal dysplasia
Has any evidence of an active infection (eg, sepsis, cytomegalovirus, or listeriosis)
Has a clinically significant infection (eg, pneumonia, pyelonephritis) within 30 days prior to screening, or ongoing chronic infection
Has evidence of active C. difficile as evidenced by positive C. difficile toxin or is having treatment for C. difficile infection or other intestinal pathogens during Screening
Has a known history of infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or chronic HBV (HBV immune participants (ie, being hepatitis B surface antigen [HBsAg] negative and hepatitis B antibody positive) may, however, be included), or hepatitis C virus (HCV) infection. Participants with documented successful treatment of HCV with sustained virological response (SVR) at 26 weeks can be enrolled
Has active or latent tuberculosis (TB), as evidenced by the following
a. A diagnostic TB test performed within 30 days of screening or during the Screening Period that is positive, defined as: i. Positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR ii. A TB skin test reaction ≥ 5 mm OR, b. Chest X-ray within 3 months of screening that is suspicious for pulmonary TB, and a positive or 2 successive indeterminate QuantiFERON tests within 30 days prior to Screening or during the Screening Period
Has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, HIV infection, organ transplantation)
Has any live vaccination within 30 days prior to Screening or is planning to receive any live vaccination during participation in the study
Has used a topical (rectal) treatment with (5-ASA) or corticosteroid enemas/suppositories within 2 weeks of the administration of the first dose of study drug
Has a history of hypersensitivity or allergies to vedolizumab IV or its components
Has received total parenteral nutrition (TPN) or albumin in the last 30 days prior to screening
Has any unstable or uncontrolled cardiovascular disorder, heart failure moderate to severe (New York Class Association III or IV), any pulmonary, hepatic, renal, GI, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise participant safety
Has had a surgical procedure requiring general anesthesia within 30 days prior to screening or is planning to undergo major surgery during the study period
Has a history of malignancy, except for the following: adequately-treated nonmetastatic basal cell skin cancer; squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to Screening; and history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to screening. Participant with remote history of malignancy (eg, >10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received and must be discussed with the sponsor on a case by-case basis prior to Screening
Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating, or neurodegenerative disease
Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of the first dose of study drug
Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening Visit
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