E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C virus infection |
Infezione cronica da virus dell’epatite C |
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E.1.1.1 | Medical condition in easily understood language |
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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 | PT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
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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 |
PK Lead-in phase is: To evaluate the steady state pharmacokinetics (PK) and confirm the dose of sofosbuvir/velpatasvir (SOF/VEL) in pediatric subjects with chronic hepatitis C virus (HCV) infection
Treatment Phase is: To evaluate the safety and tolerability of SOF/VEL for 12 weeks in paediatric subjects with chronic HCV |
L’obiettivo primario della fase di lead-in (iniziale) di farmacocinetica (pharmacokinetics, PK) è: - Valutare la farmacocinetica (PK) allo stato costante e confermare la dose di sofosbuvir/velpatasvir (SOF/VEL) nei soggetti pediatrici con infezione cronica da virus dell’epatite C (HCV)
L’obiettivo primario della fase di trattamento del presente studio è: - Valutare la sicurezza e la tollerabilità di SOF/VEL per 12 settimane nei soggetti pediatrici con HCV cronica |
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E.2.2 | Secondary objectives of the trial |
PK Lead-in Phase is: To evaluate the safety, tolerability, and antiviral activity of 7 days of dosing of SOF/VEL in paediatric subjects with chronic HCV
Treatment Phase is: Determine the efficacy of SOF/VEL for 12 weeks in paediatric subjects with chronic HCV infection, as assessed by the proportion of subjects with SVR 12 weeks after cessation of treatment; Determine the proportion of subjects with SVR 4 and 24 weeks; Evaluate the proportion of subjects with virologic failure; Evaluate the kinetics of circulating HCV RNA during treatment and after cessation of treatment; Evaluate the emergence of viral resistance to SOF and VEL during treatment and after cessation of treatment; Evaluate the effect of treatment with SOF/VEL on QoL; Evaluate the effect of SOF/VEL on growth and development of paediatric subjects during and after treatment; Evaluate the acceptability, including palatability, of formulations used |
Gli obiettivi secondari della fase di trattamento dello studio sono: - Determinare l’efficacia di SOF/VEL per 12 settimane nei soggetti pediatrici con infezione cronica da HCV, valutata in base alla percentuale di soggetti con risposta virologica sostenuta (sustained virological response, SVR) 12 settimane dopo la cessazione del trattamento (SVR12) - Determinare la percentuale di soggetti con SVR a 4 e a 24 settimane dopo la cessazione del trattamento (SVR4 e SVR24) - Valutare la percentuale di soggetti con fallimento virologico, tra cui episodi virali/mancata risposta e recidiva - Valutare la cinetica dell’RNA HCV circolante durante il trattamento e dopo la cessazione del trattamento - Valutare l’insorgenza della resistenza virale a SOF e VEL durante il trattamento e dopo la cessazione del trattamento - Valutare l’effetto del trattamento con SOF/VEL sulla qualità della vita misurata mediante il questionario pediatrico sulla qualità della vita PedsQL™ - Valutare l’effetto di SOF/VEL s |
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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 |
Amend#1-Tue Sep 20 00:00:00 CEST 2016-Pharmacogenomics substudy-To identify or validate genetic markers that may be predictive of the natural history of disease, response to therapy, and/or tolerability of medical therapies through genetic discovery research in subjects who provide their separate and specific consent for the Pharmacogenomics substudy |
Amend#1-Tue Sep 20 00:00:00 CEST 2016-Sottostudio di farmacogenomica-Identificare o convalidare i marcatori genetici che potrebbero essere predittivi della storia naturale della malattia, della risposta alla terapia e/o della tollerabilità delle terapie mediche tramite un’indagine di ricerca genetica nei soggetti che forniscono il proprio consenso specifico e separato per il sottostudio farmacogenomico |
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E.3 | Principal inclusion criteria |
1) Parent or legal guardian able to provide written informed consent prior to any screening evaluations and willing to comply with study requirements. Subjects will provide assent if possible, in accordance with IRB/IEC/local requirements and the Investigator's discretion. 2) 3 years to < 18 years of age as determined at Day 1 3) Chronic HCV-infection (≥ 6 months) as documented by prior medical history or liver biopsy 4) HCV RNA ≥ 1000 IU/mL at Screening 5) Subjects must have a determination of prior treatment status: a) Treatment-naïve is defined as having never been exposed to an approved or experimental HCV-specific direct acting antiviral agents or prior treatment of HCV with interferon or ribavirin. b) Treatment-experienced is defined as prior treatment failure or intolerance to a regimen containing interferon with or without RBV and with or without a protease inhibitor that was completed at least 8 weeks prior to Day 1. c) Interferon intolerant: Subject who discontinued therapy (≤ 12 weeks total) due to ≥ 1 adverse event 6) A negative serum pregnancy test is required at screening and a negative urine test is required at Day 1 for female subjects of child bearing potential. 7) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception. 8) Lactating females must agree to discontinue nursing before the IMP is administered. 9) Subject must be able to comply with the dosing instructions for study drug administration and be able to complete the study schedule of assessments. |
Si veda sezione 4.2 del Protocollo |
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E.4 | Principal exclusion criteria |
1) Prior use of an HCV NS5A inhibitor 2) Current or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage) 3) Any of the following laboratory parameters at screening: a) INR > 1.2 x ULN b) Platelets < 50,000/mm3 c) albumin < 3.5 g/dL d) ALT > 10 x the upper limit of normal (ULN) e) AST > 10 x ULN f) Direct bilirubin > 1.5 x ULN g) Estimated glomerular filtration rate < 90 mL/min/1.73m2, as calculated by the Schwartz Formula 4) Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency) 5) Evidence of hepatocellular carcinoma (HCC) or other malignancy (with the exception of certain resolved skin cancers) 6) Co-infection with HIV, acute HAV, or HBV 7) Current or prior history of any of the following: a) Significant cardiovascular, pulmonary, or neurological disease b) Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications c) History of solid organ or bone marrow transplantation d) Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years. 8) Clinically-relevant alcohol or drug abuse within 12 months of screening. 9) Sexually-active males or females of childbearing potential who are |
Si veda sezione 4.3 del Protocollo |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the PK Lead-in Phase is to determine steadystate PK, is AUCtau of VEL, SOF, and its major metabolite (GS-331007). The primary endpoint of the Treatment Phase is assessment of any AEs with a focus on AEs that lead to discontinuation of study drug. |
Per la fase di lead-in di PK, i parametri di PK plasmatici principali sono AUCtau per SOF, GS-331007, e VEL.
Per la fase di trattamento, l’endpoint di sicurezza primario è l’analisi di tutti gli EA, in particolare sugli eventi che determinano l'interruzione del tratameno |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PK lead in phase - Day 7 Treatment phase - SVR 12 weeks |
Fase di lead-in di PK - Giorno 7 Fase di trattamento - SVR 12 settimane |
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E.5.2 | Secondary end point(s) |
The secondary endpoints of the PK Lead-in Phase are: - Antiviral activity measurements, including assessment of HCV RNA from baseline through Day 7. - Any AE leading to permanent discontinuation of study drug.
The secondary endpoints of the Treatment Phase are: - The proportion of subjects with sustained virological response (SVR) 12 weeks after cessation of treatment (SVR12). SVR12 is the key efficacy endpoint. - The proportion of subjects with HCV RNA < LLOQ at 4 or 24 weeks after cessation of treatment (SVR4 and SVR24). - The proportion of subjects with virologic failure, including breakthrough/nonresponse and relapse - The proportion of subjects with HCV RNA < LLOQ on treatment - Emergence of viral resistance to SOF and /or VEL during treatment and treatment is discontinued - HCV RNA change from Baseline/Day 1 - Quality of life endpoints and neuropsychiatric assessments as measured by PedsQL™ Pediatric Quality of Life survey - Growth and development measurements including height and weight percentiles, Tanner Stage, parental height, and bone age - Acceptability assessed by swallowability and palatability
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Gli endpoint secondari della fase di lead-in PK sono: - Misurazioni di attività antivirale, compresa la valutazione di HCV RNA dal basale a 7 giorni. - Qualsiasi AE che ha portato alla sospensione permanente del farmaco in studio.
Gli endpoint secondari della fase di trattamento sono: - La percentuale di soggetti con risposta virologica sostenuta (SVR) 12 settimane dopo la fine del trattamento (SVR12). SVR12 è l'endpoint chiave di efficacia. - La percentuale di soggetti con HCV RNA <LLOQ a 4 o 24 settimane dopo l'interruzione del trattamento (SVR4 e SVR24). - La percentuale di soggetti con fallimento virologico, compresi breakthrough / mancata risposta e ricaduta - La percentuale di soggetti con HCV RNA <LLOQ sul trattamento - Insorgenza di resistenza virale per SOF e / o VEL durante il trattamento e il trattamento viene interrotto - Cambiamento di HCV RNA dal basale / Giorno 1 - Endpoint sulla qualità della vita e valutazioni neuropsichiatriche come misurato da PedsQL™ Pediatric Quality of Life survey - le misure di crescita e di sviluppo, tra cui altezza e peso percentili, stadio di Tanner, l'altezza dei genitori, e l'età ossea - Accettabilità valutata da deglutibilità e appetibilità
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
SVR 4, 12 and 24 weeks |
SVR 4, 12 e 24 Settimane |
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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 | No |
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 | 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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | Information not present in EudraCT |
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 |
Belgium |
Italy |
United Kingdom |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |