An open-label study to evaluate the efficacy, safety and the healing of the mucosa of the bowel of vedolizumab in subject with early onset of ulcerative colitis versus subject with longer exisiting ulcerative colitis

Phase 1

• Conditions: lcerative colitis; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2014-005443-40-HU
• Lead Sponsor: Academic Medical Center, Gastroenterology

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-08-30
• Last Update Posted: 8 January 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 120

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 endscopies 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 4 weeks before baseline.
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 since diagnosis
or: steroid dependency at any dose
and additionally, but not mandatory, lack of efficacy of thiopurines or intolerance to thiopurines (any duration). Patients who are using thiopurines (azathioprine, 6-mercaptopurine or 6-thioguanine) at screening must have used them for > 3 months (last 4 weeks at stable dose).

GROUP 2 (LATE UC)
1. Diagnosis of UC > 4 years 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 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 IBD incl. aminosalicylates and thiopurines and corticosteroids. Steroids will be tapered by protocol by week 26. Anti-TNF must be discontinued for > 4 weeks before baseline.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1. Previous exposure to any anti-integrin antibodies including vedolizumab, a4ß7 antibodies, ß7 antibodies, anti-MADCAM-1.
2. Contraindication for endoscopy.
3. History of colonic dysplasia or colonic cancer.
4. Subjects with a pouch.
5. Extensive colonic resection, i.e. subtotal or total colectomy with <15 cm colon remaining.
6. Received other biologics within the last 4 weeks of the baseline visit.
7. Use of 5-ASA or corticosteroid enemas/suppositories within 2 weeks of enrollment.
8. Chronic hepatitis B or C infection.
9. Subjects with ALT or AST 3x the upper limit of normal measured at screening.
10. Evidence of or treatment for C. difficile infection or other intestinal pathogen at screening within 4 weeks prior to enrollment.
11. Active or latent tuberculosis.
12. Conditions which in the opinion of the investigator may interfere with the subject’s ability to comply with the study procedures.
13. Received any investigational drug in the past 30 days or 5 half-lives, whichever is longer.
14. Positive PML subjective symptom checklist before enrollment.
15. Cancer (other than resected cutaneous basal cell or squamous cell carcinoma that has been treated with no evidence of recurrence). Subject with a history of cancer and a documented 2-year disease free period before screening, may enter the study.
16. Early UC group: previous exposure to any anti-TNF.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified