An Open Label Phase 4 Study to Evaluate Efficacy of Early Versus Late Use of Vedolizumab in Ulcerative Colitis

• Status: Completed
• Trial end date: 2020-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This multi-centre open label study will involve a minimum of 120 patients in 2 cohorts: 60 patients with 'early UC' defined as disease duration < 4 years and no other treatments than aminosalicylates and/or corticosteroids and 60 patients with 'late UC' defined as active disease despite treatment with immunosuppressives (IS) and/or anti-TNF. Patients wih intolerance to IS AND anti-TNF will also be allowed in the latter group. Participants will be treated with 12 months of open label vedolizumab and undergo monitoring of endoscopic, histological and clinical disease parameters. No randomization or blinding will be performed but the study management will make sure recruitment in either study group is comparable for number and profile of patients (extent of disease and on/off corticosteroids).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Geert D'Haens
• Collaborator: Takeda
• Treatments: Vedolizumab

Criteria

Inclusion Criteria:

1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.

2. The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

3. Age 18 to 80

4. Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]).

5. Established diagnosis of ulcerative colitis with histopathological confirmation available in the record of the patient.

6. Moderate to severe active UC (total Mayo score > 6) with objective evidence of inflammation that can be visualized on endoscopy. All endoscopies will be video-taped for later review, rereading and quality assurance. Patients must have an endoscopic Mayo score of 2 or 3.

7. Anti-TNF discontinued for at least 6 weeks

8. Written informed consent must be obtained and documented

GROUP 1 (EARLY UC)

1. Diagnosis of UC < 4 years prior to enrollment confirmed by clinical, endoscopic and histopathological evidence.

2. Demonstrated failure to respond to aminosalicylates or intolerance to aminosalicylates and: failure to respond to topical or systemic corticosteroids or intolerance to corticosteroids or: need for > 1 course of steroids per year or: steroid dependency at any dose and additionally, but not mandatory, lack of efficacy of thiopurines or intolerance to thiopurines (azathioprine, 6-mercaptopurine or 6-thioguanine) (any duration). Patients who are using thiopurines at screening must have used them for > 3 months (last 4 weeks at stable dose).

GROUP 2 (LATE UC)

1. Diagnosis of UC confirmed by clinical, endoscopic and histopathological evidence.

2. Demonstrated failure to respond to aminosalicylates or intolerance to aminosalicylates and: failure to respond to at least 3 months of thiopurines (TP) or intolerance to TP and: failure to respond to at least 1 anti-TNF or intolerance to anti-TNF or loss of response to at least 1 anti-TNF. Loss of response to anti-TNF is defined as recurrence of symptoms during maintenance dosing following prior clinical benefit.

May continue stable dose of conventional therapies for Inflammatory Bowel Disease ( IBD) including aminosalicylates and thiopurines and corticosteroids. Steroids will be tapered by protocol by week 14. Anti-TNF must be discontinued for > 6 weeks.

Exclusion Criteria:

1. Prior treatment with vedolizumab.

2. Contraindication for endoscopy.

3. History of colonic dysplasia/cancer

4. Extensive colonic resection, i.e. subtotal or total colectomy with <15 cm colon remaining

5. Received other biologics within the last 4 weeks of baseline

6. Use of 5-ASA or corticosteroid enemas/suppositories within 2 weeks of enrollment

7. Chronic hepatitis B or C infection

8. Evidence of or treatment for C. difficile infection or other intestinal pathogen at screening within 4 weeks prior to enrollment

9. Active or latent tuberculosis

10. Conditions which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures.

11. Received any investigational drug in the past 30 days or 5 half-lives, whichever is longer.

12. Positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist before enrollment