E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative Colitis and Crohn’s Disease |
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E.1.1.1 | Medical condition in easily understood language |
Ulcerative colitis is an inflammatory disease of the large bowel. Crohn’s disease is an inflammatory disease of the gastrointestinal tract. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013099 |
E.1.2 | Term | Disease Crohns |
E.1.2 | System Organ Class | 100000004856 |
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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 |
To monitor ongoing safety in subjects with ulcerative colitis and Crohn´s disease and to provide access to vedolizumab for qualifying subjects who, in the opinion of the investigator, continue to derive benefit from vedolizumab and for whom continued treatment with vedolizumab is desired because there is no other comparable product available or the subject may be expected to develop worsening of disease if they were to modify treatment |
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E.2.2 | Secondary objectives of the trial |
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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 |
XAP-PK Substudy (Protocol Amendment 5, 07-Feb-17): Subjects entering the Vedolizumab-4013 extended access program (XAP) from the C13008 clinical study will undergo a decrease in dosing frequency from every 4-week (Q4W) dosing to an every 8-week (Q8W) dosing regimen. Subjects making the transition between the two studies and moving to Q8W dosing may consent to take part in a pharmacokinetic (PK) sub-study (XAP-PK). The XAP-PK sub-study will assess the PK of vedolizumab (serum vedolizumab concentration and anti-vedolizumab antibodies [AVAs]) in subjects who move from Q4W dosing to Q8W dosing. Trough PK samples will be drawn immediately before the last dose in the C13008 study (T0), and in addition, before the first Q8W dose at Week 8 (T+1) and the second Q8W dose (T+2) at Week 16 to quantify PK at the new steady state for Q8W dosing. Should the subject lose clinical response to vedolizumab over time after the transition to Q8W dosing, further trough blood samples will be drawn for PK immediately prior to first dose after decision to return to Q4W dosing (T’0) and in addition before the next 2 doses (T’+1, T’+2), to quantify PK at the new steady state for Q4W dosing. The XAP-PK sub-study will also assess the proportion of subjects who move from Q4W dosing to Q8W dosing and remain on Q8W dosing through to Week 56. Vedolizumab PK will also be described based on trough concentrations by baseline subject factors influencing variability in subjects who remain on Q8W dosing, as well as those who return to Q4W dosing, either regaining response or not.
XAP-PK Substudy Objectives: * To assess drug concentration during changes in dosing regimens. * To understand the effects of AVAs on a subject’s ability to maintain or regain clinical response during changes in dosing regimens. * To understand the proportion of subjects who maintain clinical response during a change in dosing regimen . * To describe vedolizumab PK based on trough concentrations by baseline subject characteristics influencing variability. * To assess pre-dose serum drug concentration and AVA in relation to efficacy and safety. |
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E.3 | Principal inclusion criteria |
Any subject who meets the inclusion criteria for the qualifying vedolizumab clinical studies and meets any of the following criteria will qualify for entry into the study: 1. Received vedolizumab (excluding comparator or placebo subjects) during participation in a qualifying vedolizumab study. 2. In the opinion of the investigator, the subject is continuing to derive benefit from vedolizumab and continued treatment with vedolizumab is desired because there is no other comparable product available or the subject may be expected to develop worsening of disease if they were to modify treatment. 3. A male subject who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose. 4. A female subject of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
PK Substudy: 5. Received vedolizumab during participation in the C13008 protocol. 6. The subject will start the main XAP study on Q8W dosing. 7. The subject or, when applicable, the subject’s legally acceptable representative, has signed and dated a written ICF for the procedures related to the XAP-PK substudy. |
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E.4 | Principal exclusion criteria |
Any subject who meets any of the exclusion following criteria will not qualify for entry into the study: 1. For the subject’s particular clinical scenario, vedolizumab is currently available to the subject through commercial channels, including reimbursement. 2. Subject has any clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements or poses a risk to the subject being in the study. 3. If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 18 weeks after participating in this study; or intending to donate ova during such time period. 4. If male, the subject intends to donate sperm during the course of this study or for 18 weeks thereafter. 5. Subject has received a live vaccine in the last 18 weeks or is in need of a live vaccine during the study or up to 18 weeks after the last study dose. |
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E.5 End points |
E.5.1 | Primary end point(s) |
* Number and percentage of subjects with adverse events (AEs) and serious AEs (SAEs) * Number and percentage of subjects with adverse events of special interest (AESIs) |
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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) |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Continue to provide access to vedolizumab for qualifying subjects (extended access program) |
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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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 81 |
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 |
Australia |
India |
Korea, Republic of |
Malaysia |
New Zealand |
Russian Federation |
Serbia |
South Africa |
Taiwan |
Turkey |
Ukraine |
Bulgaria |
Estonia |
Hungary |
Italy |
Latvia |
Poland |
Romania |
Slovakia |
Czechia |
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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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Subjects will remain in the study until vedolizumab is available to the subject through commercial channels, including reimbursement, for the subject’s clinical scenario or until subject withdrawal, whichever is sooner. Subjects will return 18 weeks after their final study infusion for a safety follow-up visit regardless of whether they remain on vedolizumab after the study (ie, they left the study due the availability of vedolizumab or they withdrew from the study for other reasons). |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |