E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
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 |
Primary:
To evaluate the efficacy of V565 555 mg three times a day (TID) in subjects with active Crohn’s disease (CD) measured by the proportion of subjects achieving response to therapy. Response is defined as reduction in the Crohn's Disease Activity Index (CDAI) scores and in inflammatory markers (C-reactive protein [CRP] or faecal calprotectin [FCP] at Day 42.
|
|
E.2.2 | Secondary objectives of the trial |
Secondary:
• further characterise the efficacy of V565 in subjects with active CD assessed by changes in CDAI scores &/or inflammatory markers
• assess the effects of V565 based on changes in Abdominal Pain & Stool Frequency instrument (PRO-2) scores
• assess safety & tolerability of V565
Pharmacokinetic:
• determine the concentration of V565 in serum & urine
Exploratory Endoscopy Objectives:
• To investigate the effect of V565 on changes in endoscopic mucosal appearance, evaluated with an overall assessment and the Simple Endoscopic Score for Crohn's Disease (SES-CD), as determined by a central reader |
|
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 |
Pharmacogenetics substudy
A blood sample for exploratory genetic research will be obtained from consenting subjects pre-dose, at Visit 3 (Day 1).
This sample may be analysed only for genes involved in the drug metabolism, safety, and clinical efficacy of V565. These samples may provide information on how individuals metabolise and react to
the study drug.
|
|
E.3 | Principal inclusion criteria |
1. History of CD (confirmed by ileocolonoscopy) of at least three
months duration prior to Visit 1
2. CDAI score of ≥220 to ≤450 during Screening
3. CRP ≥5 mg/L (or, if CRP is normal, FCP≥ 250 μg/g ) at Screening
4. Active CD of ileum and/or colon as determined by the baseline
ileocolonoscopy
5. Female subjects must not be pregnant and male and female subjects must agree to use effective contraception throughout the study and for 90 days after the last dose of study drug.
6. Subject must have failed or experienced intolerance to at least
one of the following: aminosalicylates, corticosteroids; immunosuppressants |
|
E.4 | Principal exclusion criteria |
The main criteria for exclusion are:
1. CD of mouth, stomach, oesophagus or duodenum which, in the
opinion of the Investigator, is likely to be causing symptoms
2. Known history of or suspicion of ulcerative colitis, indeterminate colitis, microscopic colitis, ischaemic co litis or radiation-induced colitis, based on medical history, endoscopy and/or histological findings.
3. Any gastrointestinal (GI) manifestations of CD that might affect
the evaluation of efficacy
4. Prior primary efficacy failure of o r secondary loss of response to
anti-TNFα therapy, or any contraindication to anti-TNFα therapy
5. The use of medications prior to the study or during the study
with the potential to affect the evaluation of efficacy
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint:
• Proportion of responders at Day 42, defined as subjects achieving both CDAI ≥70-point reduction from Baseline OR CDAI score <150, AND a reduction of ≥40% fro m the baseline value of CRP or FCP |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints:
• Proportion of subjects achieving a ≥100-point reduction in CDAI score and a concomitant reduction of 50% in CRP o r FCP at Day 42
• Proportion of subjects achieving a ≥70-point reduction in CDAI score at Day 42
• Proportion of subjects achieving a ≥100-point reduction in CDAI score at Day 42
• Proportion of subjects achieving a CDAI score of <150 CDAI at Day 42
• Changes from Baseline in scores for PRO-2 at Day 14 and Day 42
Safety Endpoints:
• Evaluations of AEs, clinical laboratory results, physical examination findings, ECGs and vital signs throughout the study
Pharmacokinetic Endpoint:
• Serum and urine concentration of V565 prior to first administration of study drug and at Day 14, Day 42, and Day 56. In addition, On Day 1, a post-dose urine sample will be obtained at the site 4 to 8 hours after the first dose of study drug.
Exploratory Endoscopy Endpoints:
• Changes from Baseline in endoscopic mucosal appearance after 42 days treatment evaluated by changes in overall mucosal appearance and changes in SES-CD as determined by a central reader.
Note: this substudy will be limited to subjects with a baseline SES-CD ≥7 (if ileum and colon are involved) or ≥4 (if only ileum is involved). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 14, Day 42, Day 56 (Day 1 as well for PK ) as specified above |
|
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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
|
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 51 |
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 |
Canada |
Czech Republic |
Germany |
Hungary |
Poland |
Slovakia |
Ukraine |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |