E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Clostridium Difficile Infection (CDI) also known as C. difficile-associated diarrhoea (CDAD) |
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E.1.1.1 | Medical condition in easily understood language |
Infection of the gut caused by bacteria called Clostridium difficile |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022661 |
E.1.2 | Term | Intestinal infection due to clostridium difficile |
E.1.2 | System Organ Class | 100000004862 |
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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 |
The primary objective of the study is to evaluate whether the extended duration fidaxomicin therapy is superior to the standard vancomycin therapy in sustained clinical cure of CDI at 30 days after end of treatment (Day 40 for vancomycin group or Day 55 for fidaxomicin group). Sustained clinical cure is defined as clinical response at Test of Cure (TOC) and no recurrence of CDI from TOC until time of assessment. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: - to compare sustained clinical cure of CDI at Day 40*, Day 55* and Day 90* - to compare clinical response of CDI at 2 days after end of treatment (Day 12 or Day 27) - to compare clinical response of CDI at Day 12* - to compare the rate of relapse at Day 90 as determined by whole genome sequencing of C. Difficile isolates from subjects who have documented recurrence after TOC* - to compare TTROD in hours - to compare recurrence rate of CDI at Day 40, Day 55 and Day 90 - to compare time to recurrence after end of treatment (only for subjects with clinical response) - to compare disease-free survival after Day 10 (only for subjects with clinical response) - to compare incidence of mortality and severity of adverse events at Day 90 - to assess change in Health Related Quality of Life from baseline to Day 12, Day 27, Day 40, Day 55 and recurrence using the EQ-5D-5L questionnaire - to compare readmissions and length of hospital stay a |
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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 |
There are two sub-studies: • Pharmacokinetic (Blood) Analysis Sub-Study involving approximately 10 patients, and • Stool Microbiome & Fecal Fidaxomicin Concentration Analysis Sub-Study involving approximately 80 patients
The sub-study objectives are as follows • To assess plasma and stool levels of fidaxomicin with extended dose regimen • To assess the comparative impact of fidaxomicin versus vancomycin on the microbiome and the lifecycle of C. difficile |
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E.3 | Principal inclusion criteria |
• Subject is 60 years of age or over. • CDI is confirmed by clinical symptoms (either >3 unformed bowel movements or ≥200ml of unformed stool (for subjects having rectal collection devices)) in the 24 hours prior to randomization and CDI test confirmed positive for presence of C. difficile toxin A or B in stool within 48 hr prior to randomization. • Independent Ethics Committee (IEC) approved written Informed Consent and privacy language as per national regulations must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). • Subject agrees not to participate in another interventional study whilst participating in this study. |
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E.4 | Principal exclusion criteria |
• Subject is taking or requiring to be treated with prohibited medications • Subject has received more than one day of dosing of any therapy for CDI within the last 48 hours • Subject has experienced more than 2 previous episodes of CDI in the 3 months prior to study enrolment • Subject is unable to swallow oral study medication. • Subject has a current diagnosis of toxic megacolon. • Subject is not willing to adhere to the provisions of treatment and observation specified in the protocol. • Subject has been randomized into this study previously, has taken any investigational drug within 28 days or 5 half lives, whichever is longer, prior to enrollment, or is currently participating in another clinical study which may influence the assessment of efficacy and/or safety endpoints of this study, in the opinion of the Sponsor. • Subject has previously participated in a CDI vaccine study • Subject has hypersensitivity to fidaxomicin, vancomycin or any of its components. • Any clinical condition which, in the opinion of the Investigator, would not allow safe completion of this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is sustained clinical cure of CDI at 30 days after end of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
30 days after end of treatment (Day 40 for vancomycin group or Day 55 for fidaxomicin group) |
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E.5.2 | Secondary end point(s) |
• Sustained clinical cure of CDI at Day 40, Day 55 and Day 90 • Clinical response of CDI at 2 days after EOT (Day 12 or Day 27) • Clinical response of CDI at Day 12 • TTROD in hours • Recurrence rate of CDI at Day 40, Day 55 and Day 90 • Time to recurrence after end of treatment (only for subjects with clinical response) • Disease-free survival after Day 10 (only for subjects with clinical response) • Rate of relapse at Day 90 as determined by whole genome sequencing of C.difficile isolates from Subjects who have documented recurrence after TOC |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 12, 27, 40 , 55, 90 depending on treatment and endpoint |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
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
| 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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 130 |
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 |
Croatia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Ireland |
Italy |
Norway |
Poland |
Portugal |
Romania |
Russian Federation |
Slovenia |
Spain |
Sweden |
Switzerland |
Turkey |
United Kingdom |
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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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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |