E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative colitis |
Colitis ulcerosa |
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E.1.1.1 | Medical condition in easily understood language |
Ulcerative colitis |
Fekélyes vastagbélgyulladás (kolitisz ulceróza) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this prospective open label study is to assess the ability of vedolizumab to promote clinical, endoscopic and histological remission in patients with active ulcerative colitis in an 'early' and a 'late' disease population after 54 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
Measures of clinical disease activity (including clinical response and remission) over the 1 year study period will be described. The mucosal healing capacity of vedolizumab treatment will be observed by assessing the endoscopic and histopathologic response to treatment over the 1 year study period. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal exclusion criteria |
1. Previous exposure to any anti-integrin antibodies including vedolizumab, α4β7 antibodies, β7 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients with clinical and endoscopic remission at Week 26 and 52-54, defined as a Mayo Clinic score ≤2 and no subscore >1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Proportion of patients with endoscopic response (decrease of 1 point or more in the Mayo endoscopic score) at Weeks 26 and 52 - Proportion of patients with clinical response (defined as reduction in Mayo clinic score of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1) at all time points - Proportion of patients with clinical remission (Mayo Clinic score ≤2 and no subscore >1) at all other time points - Proportion of patients with corticosteroid-free clinical remission (Mayo Clinic score ≤2 and no subscore >1) at all other time points - Proportion of patients with normalized serum CRP at all time points - Proportion of patients with 25%, 50% and 75% reduction in the Geboes histology score at Weeks 26 and 52 - Proportion of patients with sustained clinical response (response at all time points after week 10) - Proportion of patients with sustained clinical remission (remission at all time points after week 10) - Proportion of patients that need to be hospitalized - Quality of life measured by IBDQ and Euroquol - Work productivity Index - Serum concentrations of vedolizumab and antibodies to vedolizumab before every infusion |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 19 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |