E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic infection with Hepatitis C virus genotype 1b with compensated cirrhosis |
Cirrosi epatica compensata HCV Genotipo 1b-correlata |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic infection with Hepatitis C virus genotype 1b with compensated cirrhosis |
Cirrosi epatica compensata HCV Genotipo 1b-correlata |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
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 | 10064844 |
E.1.2 | Term | Compensated cirrhosis |
E.1.2 | System Organ Class | 100000004871 |
|
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 | 10019744 |
E.1.2 | Term | Hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
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 assess efficacy (SVR rate) of MK5172 (Grazoprevir)/MK8742 (Elbasvir) for 12 weeks without RBV in G1b patients with compensated cirrhosis (Child-Pugh A5 to A6) previously failing first gen. PI or non responders to PR. |
Valutazione dell'efficacia (intesa come tasso SVR) di MK5172 (Grazoprevir)/MK8742 (Elbasvir) per 12 settimane senza RBV in pazientiRBV in pazienti adulti HCV positivi di Genotipo 1b, con cirrosi compensata (Child-Pugh da A5 a A6) che precedentemente abbiano fallito la terapia con PI di prima generazione o non abbiano risposto a PR. |
|
E.2.2 | Secondary objectives of the trial |
Tolerability measured by the frequency of patients with any Adverse Events or laboratory abnormalities. |
Tollerabilità misurata dalla frequenza di pazienti che presentano Eventi Avversi o anomalie di laboratorio |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent form signed, 2. Age > 18 years, 3. Chronic infection with Hepatitis C virus genotype 1b, 4. HCV RNA > 100 IU/mL, 5. HCV patients previously treated by PR with no response or previously treated with first generation PIs (boceprevir, telaprevir, simeprevir) and failing therapy, 6. Subjects with compensated cirrhosis with Child-Pugh score ranging between A5 to A6. Cirrhosis defined by liver biopsy (METAVIR F4) or non-invasive methods (transientelastography (FibroScan) > 12.5 KPa; or FibroTest or FibroSure > 0.75 with APRI >2), 7. Hepatic Venous Pressure Gradient (HVPG) > 6 mmHg (only in selected sites), 8. Albumin level ≥ 3.0 g/dl, 9. Platelet count ≥ 75 x 103/μL.
|
1. Soggetti che diano Consenso Informato Scritto, 2. Età >18 anni, 3. Infezione cronica con Virus dell’Epatite C di genotipo 1b, 4. HCV RNA > 100 IU/mL, 5. pazienti precedentemente trattati con PR senza risposta o con PI di prima generazione (boceprevir, telaprevir, simeprevir) ma che abbiano riportato un fallimento, 6. soggetti con cirrosi compensata aventi un Child-Pugh score compreso tra A5 e A6. Diagnosi di cirrosi mediante biopsia (METAVIR F4) o procedura non invasiva (Fibroscan > 12.5 KPa; FibroTest o FibroSure > 0.75 e APRI >2), 7. Hepatic Venous Pressure Gradient (HVPG) > 6 mmHg (solo in centri selezionati), 8. soggetti con Albumina ≥3.0 g/dl, 9. Conta piastrinica ≥75 x 103/μL.
|
|
E.4 | Principal exclusion criteria |
1. Child-Pugh score greater than CP-A6, 2. Patients with HCV genotype 1a, 2, 3, 4, 5, 6, 3. Have any serious or active medical illness which, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance, 4. HIV or chronic hepatitis B virus (HBV) infection (HBsAg positive), 5. Decompensated cirrhosis/previous decompensation, 6. Pregnancy, 7. Breast-feeding, 8. Known hypersensitivity to Grazoprevir, Elbasvir or any of its components, 9. Albumin level < 3.0 g/dl, 10. Platelet count < 75 x 103/Μl, 11. Concomitant participation in any clinical trial.
|
1. Soggetti con cirrosi aventi un Child-Pugh maggiore di A6, 2. pazienti HCV+ infettati da genotipo 1a,2,3,4,5,6, 3. soggetti con comorbidità attive serie che a opinione del medico interferirebbero con il trattamento o la valutazione o la compliance, 4. positività a virus dell’HIV e/o dell’HBV, 5. cirrosi scompensata in corso o pregressa, 6. gravidanza, 7. allattamento in corso, 8. nota ipersensibilità a Grazeprovir, Elbasvir o qualsiasi dei loro componenti 9. soggetti con Albumina <3.0 g/dl 10. soggetti con conta piastrinica <75 x 103/μL, 11. soggetti partecipanti ad altre sperimentazioni cliniche
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Sustained virologic response rates 12 weeks after discontinuation of therapy (SVR12). SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug. |
Tasso di Risposta Virologica sostenuta 12 settimane dopo l'interruzione del trattamento (SVR12). SVR12 é definito come HCV RNA < limite minimo di quantificazione (LLOQ) 12 settimane dopo l'ultima dose di farmaco sperimentale. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks following the last dose of study drug. |
12 settimane dopo l'ultima dose di farmaco sperimentale |
|
E.5.2 | Secondary end point(s) |
Proportion of participants experiencing viral relapse. Viral relapse is defined as HCV RNA ≥ LLOQ during the posttreatment period after having achieved HCV RNA < LLOQ at end of treatment. |
Percentuale di pazienti che vanno incontro a recidiva virale. La recidica virale è definita come HCV RNA ≥ LLOQ nel periodo successivo al trattamento dopo aver raggiunto HCV RNA < LLOQ alla fine del trattamento. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 12 to post-treatment week 12 |
dalla settimana 12 alla settimana 12 post-trattamento |
|
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 | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
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 | 21 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 15 |
E.8.9.2 | In all countries concerned by the trial days | 0 |