| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HCV-1 with insulin resistance |
| epatite C genotipo 1 con insulino resistenza |
|
| E.1.1.1 | Medical condition in easily understood language |
| HCV-1 with insulin resistance |
| epatite C genotipo 1 con insulino resistenza |
|
| 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 | 14.1 |
| 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 |
| Sustained Virological Response (24w SVR) with a triple combination therapy consisting of PEG-IFN plus Ribavirin Plus Boceprevir in “ difficult to retreat HCV-1 patients” who have failed previous treatment with PEG-IFN and Ribavirin and have insulin resistance at baseline. SVR will be defined as undetectable serum HCV-RNA 24 weeks after cessation of antiviral therapy |
| valutare il tasso di risposta virologica sostenuta ottenuta a 24 settimane (24w SVR), che si ottiene con una triplice terapia con PEG-IFN più Ribavirina più Boceprevir in pazienti affetti da HCV-1 e con resistenza insulinica, già risultati non responsivi ad un precedente trattamento con duplice terapia con PEG-IFN e Ribavirina |
|
| E.2.2 | Secondary objectives of the trial |
1.assessment of the evolution and selection of Boceprevir resistant variants during retreatment with triple therapy in HCV-1 infected patients with baseline insulin resistance,
2.assessment of the effect of several variables, including baseline HOMA-IR levels, BMI, liver disease stage and the pattern of previous response to dual PEG-IFN plus Ribavirin therapy, on early and SVR to retreatment with triple therapy,
3.assessment of the effect of insulin resistance at baseline on the virological response during the 4 week lead-in phase and at week 8 after adding Boceprevir |
1.valutare l’evoluzione e la selezione di mutanti virali con resistenza a BOC durante il trattamento con triplice terapia in pazienti con resistenza insulinica.
2.valutare le variabili che influenzano la risposta alla triplice terapia, inclusi i livelli basali di HOMA-IR, IMC, stato di malattia del fegato e il modello di risposta alla precedente terapia duale con PEG-IFN più Ribavirina
3.valutare l'effetto della resistenza insulinica al basale sulla risposta virologica precoce durante le 4 settimane di lead-in e alla settimana 8 dopo l'aggiunta di Boceprevir . |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Each subject must have >= 18 years of age.
2.Each subject must have quantifiable serum HCV-RNA
3.Each subject must have infection with HCV-1
4.Each subject must have HOMA IR > 2.5 in two determinations made 4 weeks apart
5.Each subject must have previous failure to achieve SVR with PEG-IFN plus Ribavirin given for a minimum of 12 weeks without dose reduction below 80% of the adequate doses of the two drugs.
6.Each subject must be with no/partial response or relapser
7.Each subject must have compensated liver disease with or without histologic or non-invasive evidence of liver cirrhosis
8.Each subject must have no contraindications to PEG-IFN or to Ribavirin as defined in the labels of the drugs to be used in combination with Boceprevir
9.If heterosexually active, a female subject of childbearing potential and a non vasectomized male subject who has a female partner of childbearing potential must agree to use 2 effective contraceptives until 6 months after therapy has ended (7 months for male subject)
10.Each subject must be able to adhere to dose and visit schedules |
1.Soggetti con età >= 18 anni
2.Soggetti con livelli misurabili di HCV-RNA serico
3.Soggetti infetti da HCV-1
4.Soggetti con HOMA IR > 2.5 in due misurazioni effettuate a 4 settimane di distanza
5.Soggetti che non hanno precedentemente raggiunto SVR con PEG-IFN più Ribavirina dopo un trattamento di almeno 12 settimane senza riduzione del dosaggio al di sotto dell'80%
6.Soggetti con nessuna risposta, parziale risposta o recidivi
7. Soggetti con epatopatia compensata, con o senza evidenza di cirrosi (istologica o non invasiva)
8. Soggetti senza controindicazione a PEG-IFN o a Ribavirina
9. I soggetti femminili eterosessualmente attivi, in grado di procreare, e soggetti maschili non vasectomizzati con una partner femmina in grado di procreare, devono accettare di utilizzare un metodo contraccettivo a doppia barriera fino alla fine del 6° mese post-terapia (7° mese per soggetti maschi)
10.Soggetti in grado di aderire al piano visite e terapeutico. |
|
| E.4 | Principal exclusion criteria |
1.Subject with coinfection with HCV genotypes other than HCV-1
2.Subject with Evidence of decompensated liver disease
3.Subject with history of ascites, hepatic encephalopathy or of bleeding varices or of severe portal hypertension
4.Subject with history or signs or symptoms or evidence of HCC.
5.Subject with other important comorbidities (Cardiovascular diseases, Type 1 diabetes or indaquately controlled type 2 diabetes, malignancies , etc)
6.Subject with Haemoglobin < 12 g/dL for females and < 13 g/dL for males
7.Subject with Neutrophils < 1500 mm3
8.Subject with Platelets < 100000 mm3
9.Subject with organ transplant
10.Subject with coinfection with HBV or HIV
11.Subject with severe psychiatric disease
12.Subject with inadequately controlled thyroid function
13.Subject with substances abuse
14.Subject with alcohol intake > 20 gr/day for females and > 30 gr/day for males
15.Subject with hypersensitivity or any other contraindication to PEG-IFN or RIBAVIRIN or to any component of the Boceprevir formulation
16.Subject with evidence of severe adverse events during previous treatment with PEG-IFN plus RIBAVIRIN, including discontinuation of therapy for severe anemia or haematologic toxicity. |
1.Soggetti con co-infezione con genotipi di HCV diversi da G1
2.Soggetti con evidenza di epatopatia scompensata
3.Soggetti con anamnesi di asciti,encefalopatia epatica o sanguinamento da varici o grave ipertensione portale
4.Soggetti con anmnesi o segni o sintomi o evidenza di HCC
5. Soggetti con altre comorbidità importanti (mal. cardiovascolari, diabete tipo 1 o tipo 2 non adeguatamente controllato, neoplasie, ecc.)
6. soggetti con Hgb < 12 g/dL (femmine) o < 13 g/dL (maschi)
7.Soggetti con neutrofili < 1500/mm3
8.Soggetti con Piastrine < 100000/mm3
9.Soggetti con trapianto d'organo
10.Soggetti co-infetti con HBV o HIV
11.Soggetti con malattie psichiatriche gravi
12.Soggetti con funzione tiroidea non adeguatamente controllata
13.Soggetti che abusano di sostanze
14.Soggetti con consumo di alcool > 20 g/giorno (femmine) o >30 g/giorno (maschi)
15.Soggetti con ipersensibilità o altre controindicazioni a PEG-IFN o ribavirina o a componenti del farmaco Boceprevir
16.Soggetti con evidenza di eventi avversi gravi durante precedente trattamento con PEG-IFN + Ribavirina, inclusa l'interruzione di trattamento per anemia grave o tossicità ematologica |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The achievement of Sustained Virological Response (24w SVR) defined as undetectable serum HCV-RNA 24 weeks after cessation of antiviral therapy |
| Raggiungimento di risposta virologica sostenuta (SVR) definita come non rilevabilità dell’HCV-RNA plasmatico alla settimana 24 di follow-up |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Raggiungimento di risposta virologica sostenuta (SVR) definita come non rilevabilità dell’HCV-RNA plasmatico alla settimana 24 di follow-up |
| Raggiungimento di risposta virologica sostenuta (SVR) definita come non rilevabilità dell’HCV-RNA plasmatico alla settimana 24 di follow-up |
|
| E.5.2 | Secondary end point(s) |
1.Analysis of Boceprevir resistance variants
2.Changes in HOMA-IR |
1.analisi delle varianti di resistenza del Boceprevir
2.cambiamenti in HOMA-IR |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.Baseline, week 4, weekly while treated with Boceprevir, monthly after stopping Boceprevir, at end of therapy, every 3 months after stopping therapy
2.At baseline and at different timepoints during and after therapy |
1. Al Basale, alla settimana 4,settimanalmente durante il trattamento con Boceprevir, mensilmente dopo l'interruzione di Boceprevir, alla fine della terapia, ogni 3 mesi dopo la fine della terapia
2. al basale e a diversi tempi durante e dopo la terapia |
|
| 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) | 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| 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 | No |
| 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 | 24 |
| E.8.9.1 | In the Member State concerned days | 0 |
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