Vedolizumab Intravenous (IV) Dose Optimization in Ulcerative Colitis

• Register: ClinicalTrials.gov
• Last refreshed on: 7 September 2021
• Main ID: NCT03029143
• Date of registration: 20/01/2017
• Prospective Registration: Yes
• Primary sponsor: Takeda
• Public title: Vedolizumab Intravenous (IV) Dose Optimization in Ulcerative Colitis ENTERPRET
• Scientific title: 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)
• Date of first enrolment: March 29, 2017
• Target sample size: 278
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03029143
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 4

Countries of recruitment

Canada, United States

Contacts

• Name: Medical Director Clinical Science
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Has a diagnosis of UC established at least 1 month prior to Screening by clinical and
endoscopic evidence and corroborated by a histopathology report.

2. 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.

3. Has evidence of UC proximal to the rectum (=15 cm of involved colon) prior to start of
vedolizumab IV dosing.

4. Has been determined to be suitable for vedolizumab IV for routine management of UC by
their physician.

5. Has 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).

6. Has demonstrated an inadequate response with, lost response to, or intolerance of at
least 1 of the following agents: immunomodulators, corticosteroids, or tumor necrosis
factor-alpha (TNF-a) antagonists. Subject who are naive to 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

7. Following Lead-in Period, the subject is assessed as having high vedolizumab drug
clearance based on a predefined Week 5 serum vedolizumab concentration threshold (<50
microg/mL).

8. Following Lead-in Period, the subject is a non-responder based on partial Mayo score
at Week 6.

Exclusion Criteria:

1. Has clinical evidence of abdominal abscess or toxic megacolon at the Screening Visit.

2. Has had an extensive colonic resection, subtotal or total colectomy.

3. Has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.

4. Has a diagnosis of Crohn's colitis or indeterminate colitis, ischemic colitis,
radiation colitis, diverticular disease associated with colitis, or microscopic
colitis.

5. Has received any of the following for the treatment of underlying disease within 30
days of screening:

1. Non-biologic therapies (eg. cyclosporine, tacrolimus, thalidomide)

2. An approved non-biologic therapy in an investigational protocol.

6. Has received any investigational or approved biologic or biosimilar agent within 60
days or 5 half-lives prior to screening (whichever is longer).

7. Has previously had prior exposure to approved or investigational anti-integrin
antibodies (e.g. natalizumab, efalizumab, etrolizumab, AMG-181, anti-MAdCAM-1
antibodies or rituximab).

8. Has previously received approved or investigational vedolizumab.

9. The subject currently requires or is anticipated to require surgical intervention for
UC during the study.

10. Has history or evidence of adenomatous colonic polyps that have not been removed, or
colonic mucosal dysplasia.

11. Has any evidence of an active infection during Screening (eg, sepsis, cytomegalovirus,
or listeriosis).

12. Has a clinically significant infection (eg, pneumonia, pyelonephritis) within 30 days
prior to screening, or ongoing chronic infection.

13. 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.

14. Has a known history of infection with human immunodeficiency virus (HIV), hepatitis B
(HBV), or chronic HBV (HBV immune subjects (ie, being hepatitis B surface antigen
[HBsAg] negative and hepatitis B antibody positive) may, however, be included), or
hepatitis C virus (HCV) infection. Subjects with documented successful treatment of
HCV with sustained virological response (SVR) at 26 weeks can be enrolled.

15. 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.

16. Has any identified congenital or acquired immunodeficiency (eg, common variable
immunodeficiency, HIV infection, organ transplantation).

17. Has any live vaccination within 30 days prior to Screening or is planning to receive
any live vaccination during participation in the study.

18. Has used a topical (rectal) treatment with (5-ASA) or corticosteroid
enemas/suppositories within 2 weeks prior to Screening.

19. Has a history of hypersensitivity or allergies to vedolizumab IV or its components.

20. Has received total parenteral nutrition (TPN) or albumin in the last 30 days prior to
screening.

21. 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 subject safety.

22. 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.

23. Has a history of malignancy, except for the following: adequately-treated
non-metastatic 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. Subjects 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.

24. Has a history of any major neurological disorders, including stroke, multiple
sclerosis, brain tumor, demyelinating, or neurodegenerative disease.

25. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom
checklist during Screening or prior to the administration of the first dose of study
drug on Day 1.

26. H


Age minimum: 18 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Colitis, Ulcerative

Intervention(s)

Drug: Vedolizumab IV

Primary Outcome(s)

Proportion of Subjects Achieving Mucosal Healing [Time Frame: Week 30]

Secondary Outcome(s)

Proportion of Subjects Achieving Clinical Response [Time Frame: Week 30]

Proportion of Subjects Achieving Clinical Response Based on Partial Mayo Score [Time Frame: Week 14]

Proportion of Subjects With Corticosteroid-Free Remission [Time Frame: Week 30]

Proportion of Subjects Achieving Durable Clinical Response [Time Frame: Weeks 14 and 30]

Proportion of Subjects Achieving Clinical Remission [Time Frame: Week 30]

Secondary ID(s)

Vedolizumab-4014

U1111-1183-0451

Source(s) of Monetary Support

Please refer to primary and secondary sponsors