E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Sclerosing Cholangitis (PSC) Inflammatory Bowel Disease (IBD) |
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E.1.1.1 | Medical condition in easily understood language |
Liver disease Inflammatory bowel disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036732 |
E.1.2 | Term | Primary sclerosing cholangitis |
E.1.2 | System Organ Class | 100000004871 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021972 |
E.1.2 | Term | Inflammatory bowel disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021973 |
E.1.2 | Term | Inflammatory bowel disease NOS |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy and safety of vedolizumab IV in non?end-stage PSC subjects with underlying IBD |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of vedolizumab IV on inflammation and alkaline phosphatase (ALP) in non?end-stage PSC subjects with underlying IBD |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
An Magnetic Resonance Elastography (MRE) sub-study will be conducted at selected qualified sites, in a maximum of approximately 50% of subjects. Only subjects from the preselected sites will be included in this study; these subjects will undergo an MRE assessment at Screening, Week 54, and Week 106 or early termination (ET) visit, unless they have contraindications to the procedure. |
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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 or, when applicable, the subject?s legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. The subject has chronic cholestatic liver disease, of at least 6 months duration, with a subsequent diagnosis of PSC, based on cholangiographic findings of intrahepatic and/or extrahepatic bile duct irregularities consistent with PSC. 4. The subject has a diagnosis of IBD (either UC, CD, or IBDU), established at least 3 months prior to enrollment by clinical and endoscopic evidence and corroborated by a histopathology report. 5. The subject is male or female and aged 18 years and older, inclusive. 6. A male subject who is non-sterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of the informed consent throughout the duration of the study and for 18 weeks after last dose. 7. A female subject of childbearing potential* who is sexually active with a non-sterilized male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study and for 18 weeks after the last dose. 8. The subject has had a colorectal cancer screen within 12 months of the Screening Visit with no signs of malignancy, dysplasia, or neoplasia. |
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E.4 | Principal exclusion criteria |
1. The subject has had previous exposure to vedolizumab 2. The subject has a history of hypersensitivity or allergies to vedolizumab 3. The subject has had previous exposure to natalizumab, efalizumab, rituximab or any other integrin antagonist 4. The subject has received any investigational or approved biologic or biosimilar agent 5. The subject has received any of the following for the treatment of underlying disease within 30 days of screening: ? Nonbiologic therapies other than those specifically listed in the protocol Section 7.3.1 Permitted Medications for the Treatment of IBD ? An approved nonbiologic therapy in an investigational protocol 6. The subject has, in the judgment of the investigator, clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes 7. The subject has any history of malignancy, except for (a) adequately treated nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has not recurred for at least 1 year prior to randomization; and (c) history of cervical carcinoma in situ that has not recurred for at least 3 years prior to randomization 8. The subject has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demylelinating or neurodegenerative disease 9. The subject has a positive response on the PML subjective symptom checklist prior to the administration of study drug |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with no worsening in Ishak fibrosis staging score, from Baseline to the Week 106 visit |
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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 subjects with a ?35% reduction in serum ALP from Baseline to the Week 106 visit. ? Change in Ishak necroinflammatory grading score from the Baseline visit to the Week 106 visit. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Bulgaria |
Canada |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Netherlands |
Poland |
Russian Federation |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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End of trial will be the date of the last visit of the last subject at the Week 120 Safety follow-up visit |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |