| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Hepatitis C Virus Infection |
| Infección crónica por el virus de la hepatitis C |
|
| E.1.1.1 | Medical condition in easily understood language |
| Hepatitis C Virus Infection |
| Infección por el virus de la hepatitis C |
|
| 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 |
1) To evaluate the efficacy of each treatment arm of MK-5172 in combination with RBV as assessed by the proportion of subjects achieving SVR12 (Sustained Virologic Response 12 weeks after the end of all study therapy), defined as HCV RNA <25 IU/mL (either TD(u) or TND) 12 weeks after the end of all study therapy.
2) To evaluate the safety and tolerability of MK-5172 in combination with RBV. |
(1) Evaluar la eficacia en cada grupo de tratamiento con MK 5172 en combinación con RBV mediante la proporción de sujetos que logren una RVS12 (respuesta virológica sostenida 12 semanas después del final del tratamiento del estudio), definida como una concentración de ARN del VHC < 25 UI/ml (OD(nc) u OND) 12 semanas después del final del tratamiento del estudio.
(2) Evaluar la seguridad y la tolerabilidad de MK 5172 en combinación con RBV. |
|
| E.2.2 | Secondary objectives of the trial |
1)Evaluate the efficacy of each treatment arm of MK5172 in combination w\RBV as assessed by the time to 1st achievement of undetectable (TND) HCV RNA
2)Evaluate the efficacy of each treatment arm of MK5172 in combination w\RBV as assessed by the proportion of subjects achieving undetectable (TND) HCV RNA and HCV RNA <25 IU/mL at Wk 2, Wk 4, Wk 12 and at the end of treatment visit
3)Evaluate the efficacy of each treatment arm of MK5172 in combination w\RBV as assessed by the proportion of subjects achieving:
-SVR4 (Sustained Virologic Response 4wks after end of all study therapy), defined as HCV RNA <25 IU/mL (either TD(u) or TND) 4wks after the end of all study therapy
-SVR24 (Sustained Virologic Response 24wks after end of all study therapy), defined as HCV RNA <25 IU/mL (either TD(u) or TND) 24wks after end of all study therapy
4)Evaluate the emergence of viral resistance-associated variants (RAV) resistant to MK5172 when administered as part of a combination regimen w\RBV |
1 Evaluar la eficacia en cada grupo de tratamiento con MK 5172 en combinación con RBV mediante el tiempo transcurrido hasta la primera consecución de una concentración indetectable (OND) de ARN del VHC.
2 Evaluar la eficacia en cada grupo de tratamiento con MK 5172 en combinación con RBV mediante la proporción de sujetos que logren una concentración indetectable (OND) de ARN del VHC y una concentración de ARN del VHC < 25 UI/ml en las semanas 2, 4 y 12 y en la visita de final del tratamiento.
(Leer objetivos 3 y 4 en el protocolo en español) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
In order to be eligible for participation in this trial, the subject must:
1. be > or = to 18 years of age on day of signing informed consent.
2. have a body weight >50 kg (111 lbs) and ? 125 kg (275 lbs).
3. have chronic, compensated HCV GT 1a infection for Part A and GT1 (1a or 1b) for Part B as defined by:
-Positive serology for HCV with HCV RNA levels > or = to 10,000 IU/mL in peripheral blood at screening, and
-Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis
4. have had no evidence of cirrhosis and/or hepatocellular carcinoma. This can be confirmed either by liver biopsy or by non-invasive methods such as fibrotest or fibroscan in countries where biopsy is not the standard method of diagnosis.
5. agree to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations (for female subject who is of childbearing potential or male subject with female sexual partner who is of childbearing potential). |
1. Tener una edad mínima de 18 años el día de firma del consentimiento informado.
2.Tener un peso corporal > 50 y < o = a 125 kg.
3.Tener una infección crónica compensada por el VHC GT1, definida como:
-Serología positiva para el VHC con una concentración de ARN del VHC > o = a 10.000 UI/ml en sangre periférica en el momento de selección y
-Ausencia (sin antecedentes médicos ni hallazgos físicos) de ascitis, varices esofágicas hemorrágicas, encefalopatía hepática u otros signos o síntomas de hepatopatía avanzada o cirrosis.
4.Haberse sometido a una biopsia hepática sin signos de cirrosis o carcinoma hepatocelular. En los países en que no se practique biopsia hepática antes del tratamiento y en los que se empleen pruebas no invasivas (por ejemplo, FibroScan o FibroTest) para estadificar la hepatopatía podrán utilizarse estos resultados para determinar la elegibilidad.
5.Have had no evidence of cirrhosis and/or hepatocellular carcinoma. This can be confirmed either by liver biopsy or by non-invasive methods such as fibrotest or fibroscan in countries where biopsy is not the standard method of diagnosis.
6.Comprometerse a utilizar dos métodos anticonceptivos aceptables desde al menos 2 semanas antes del día 1 y seguir utilizándolos hasta al menos 6 meses después de la última dosis del fármaco del estudio o durante más tiempo si así lo dictan las normativas locales (para las mujeres en edad fértil y los varones con parejas en edad fértil). |
|
| E.4 | Principal exclusion criteria |
Subject will be excluded from participating in the trial if the subject:
1) has a non-GT 1 HCV infection, including a mixed GT infection (with a non-GT 1) or a non-typeable genotype.
2) is NOT treatment naïve, i.e. subject has had previous treatment with any interferon, ribavirin, approved or experimental direct acting antiviral(s), or other investigational therapies for HCV.
3) As determined by documented records, subject is HIV positive or known to be coinfected with hepatitis B virus (HBsAg positive).
4) has evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC.
5) has pre-existing psychiatric condition(s)
6) has any known medical condition that could interfere with the subjects participation in and completion of the trial
7) has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years
8) (female) is pregnant, lactating, expecting to conceive or donate eggs, or is of childbearing potential and unwilling to commit to two methods of birth control throughout treatment and after the completion of all treatment
9) is a male whose female partner(s) are pregnant
10) has exclusionary laboratory values as listed in the protocol
i) Hemoglobin <12 g/dL for females and <13 g/dL for males.
ii) Neutrophils <1.5 x 103/uL (<1.2 x 103/uL for Blacks).
iii) Platelets <150 x 103/uL
iv) Direct bilirubin >1.5 x ULN (upper limit of normal) of the laboratory reference range
v) Serum glucose:
- For subjects not previously diagnosed with diabetes mellitus, > or = to ULN mg/dL (fasting) unless HbA1c < or = to 7%.
- For subjects previously diagnosed with diabetes mellitus, HbA1c > 8.5%.
vi) PT/PTT values > 10% above laboratory reference range
vii) Anti-nuclear antibodies (ANA) > 1:320
viii) ALT > 350IU/L
ix) AST > 350 IU/L |
Se excluirá de participar en el ensayo a un sujeto que:
1.Tenga infección por un VHC distinto del GT1, incluida una infección mixta (con un VHC distinto del GT1) o por un genotipo no tipificable.
2.NO sea NTP, es decir, el sujeto ha recibido tratamiento previo con cualquier interferón, RBV, AAD aprobados o experimentales u otros tratamientos en investigación para el VHC.
3.Según lo determinado mediante los registros documentados, el sujeto está infectado por el VIH o se sabe que presenta coinfección por el virus de la hepatitis B (positividad para el HBsAg).
4.Muestre indicios de carcinoma hepatocelular (CHC) o se encuentra en evaluación por un CHC.
5.Presente un trastorno psiquiátrico preexistente
6.Tenga signos de una neoplasia maligna activa o sospechada o antecedentes de una neoplasia maligna en los cinco años anteriores
7.(mujeres) Esté embarazada, en período de lactancia, prevea concebir o donar óvulos o esté en edad fértil y no se muestre dispuesta a utilizar dos métodos anticonceptivos durante el tratamiento y tras su finalización
8.Sea un varón cuya pareja está embarazada
9.Presente valores analíticos que sean motivo de exclusión:
-Hemoglobina < 12 g/dl en las mujeres y < 13 g/dl en los varones.
-Neutrófilos < 1,5 x 103/µl (< 1,2 x 103/µl en la raza negra).
-Plaquetas < 150 x 103/µl.
-Bilirrubina directa > 1,5 veces el límite superior de la normalidad (LSN) del intervalo de referencia del laboratorio
-Glucemia:
En sujetos sin diagnóstico previo de diabetes mellitus: > o = a LSN mg/dl (en ayunas) salvo que la HbA1c sea < o = a 7%.
-En sujetos con diagnóstico previo de diabetes mellitus, HbA1c > 8,5%.
-Valores de TP/TTP > 10% por encima del intervalo de referencia del laboratorio.
-Anticuerpos antinucleares (ANA) > 1:320.
-ALT > 350 UI/l.
-AST > 350 UI/l. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint will be the proportion of subjects achieving SVR12 in each treatment arm. |
| El objetivo principal de eficacia de este estudio consiste en calcular las tasas de RVS12 de cada uno de los grupos de tratamiento |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| SVR12 (12 weeks after completion of therapy) |
| RVS12 (12 semanas después de completar la terapia) |
|
| E.5.2 | Secondary end point(s) |
1. the time to first achievement of undetectable (TND) HCV RNA;
2. the proportion of subjects achieving undetectable (TND) HCV RNA and HCV RNA < 25 IU/mL at Week 2, Week 4, and Week 12 and End of Treatment visit.
3. the proportion of subjects achieving SVR4 and SVR24.
4. the emergence of antiviral resistance to MK-5172 when administered as part of a combination regimen with RBV |
1.Tiempo hasta la primera consecución de una concentración indetectable de ARN del VHC (OND).
2.Proporción de sujetos que logren una concentración indetectable de ARN del VHC (OND) y una concentración de ARN del VHC < 25 UI/ml en las visitas de las semanas 2, 4 y 12 y de final del tratamiento.
3.Proporción de sujetos que logren una RVS4 y RVS24.
4.Aparición de resistencia a MK 5172 cuando se administra como parte de un régimen combinado con RBV. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Week 2, Week 4, and Week 12, End of Treatment visit, SVR4 (12 weeks after completion of the therapy) and SVR24. (12 weeks after completion of the therapy) |
| Semanas 2, 4 y 12, final del tratamiento, RVS4 (12 semanas después de completar la terapia) y RVS24 (24 semanas después de completar 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 | Yes |
| 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 | 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) | 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 | 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| 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 |
| Australia |
| Israel |
| Italy |
| New Zealand |
| Spain |
| 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 | 4 |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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