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    Summary
    EudraCT Number:2015-001483-19
    Sponsor's Protocol Code Number:MK-3682-021
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2016-01-11
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2015-001483-19
    A.3Full title of the trial
    A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-3682B (MK-5172 + MK-3682 + MK-8408 Fixed Dose Combination (FDC)) in Subjects with Chronic HCV GT1 or GT3 Infection who have failed a Direct Acting Antiviral Regimen
    Ensayo clínico de fase II, abierto y aleatorizado para estudiar la eficacia y la seguridad del tratamiento combinado MK-3682B (MK-5172 + MK-3682 + MK-8408 en combinación de dosis fijas (CDF)) en sujetos con infección crónica por el VHC de GT1 o GT3 que no han respondido a un tratamiento antiviral de acción directa
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    MK-3682B (MK-5172 + MK-3682 + MK-8408 Fixed Dose Combination (FDC)) in HCV GT1 or GT3 DAA Failures
    MK3682B (combinación de dosis fijas de MK5172 + MK3682 + MK8408) en la infección por VHC de GT1 o de GT3 sin respuesta a AAD
    A.3.2Name or abbreviated title of the trial where available
    MK-3682B (MK-5172 + MK-3682 + MK-8408 Fixed Dose Combination (FDC)) in HCV GT1 or GT3 DAA Failures
    MK3682B (combinación de dosis fijas de MK5172 + MK3682 + MK8408) en la infección por VHC
    A.4.1Sponsor's protocol code numberMK-3682-021
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck Sharp & Dohme de España S.A.
    B.5.2Functional name of contact pointInvestigación Clínica
    B.5.3 Address:
    B.5.3.1Street AddressC/ Josefa Valcárcel, 38
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28037
    B.5.3.4CountrySpain
    B.5.4Telephone number+34913210600
    B.5.5Fax number+34913210590
    B.5.6E-mailensayos_clinicos@merck.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameMK-3682B (Fixed dose combination of MK-5172 (50mg); MK-3682 (225 mg); Mk-8408 (30 mg) per tablet)
    D.3.2Product code MK-3682B
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMK-5172
    D.3.9.2Current sponsor codeMK-5172
    D.3.9.3Other descriptive nameMK-5172
    D.3.9.4EV Substance CodeSUB30825
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMK-8408
    D.3.9.2Current sponsor codeMK-8408
    D.3.9.3Other descriptive nameMK-8408
    D.3.9.4EV Substance CodeSUB126012
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMK-3682
    D.3.9.2Current sponsor codeMK-3682
    D.3.9.3Other descriptive nameMK-3682
    D.3.9.4EV Substance CodeSUB168240
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number225
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Rebetol
    D.2.1.1.2Name of the Marketing Authorisation holderMerck, Sharp & Dohme Corp.
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRebetol
    D.3.2Product code Rebetol
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRibavirin
    D.3.9.1CAS number 36791-04-5
    D.3.9.3Other descriptive nameRebetol
    D.3.9.4EV Substance CodeSUB10297MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Hepatitis C infection
    Infeccion por Hepatitis C
    E.1.1.1Medical condition in easily understood language
    Hep-C
    Hepatitis C
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    (1)To evaluate the efficacy of the combination regimen of MK-5172, MK-3682 and MK-8408 with or without ribavirin as assessed by the proportion of subjects in each arm achieving SVR12 (Sustained Virologic Response 12 weeks after the end of all study therapy), defined as HCV RNA <LLOQ (either TD[u] or TND) 12 weeks after the end of all study therapy.
    (2)Objective: To evaluate the safety and tolerability of the combination regimen of MK-5172, MK-3682 and MK-8408 with or without ribavirin to subjects in each arm.
    (1) Evaluar la eficacia del régimen de combinación de MK 5172, MK 3682 y MK8408 con o sin Rivabirina mediante la proporción de sujetos de cada grupo que logren una RVS12 (respuesta virológica sostenida 12 semanas después del final de todo del tratamiento del estudio), definida como un ARN del VHC <LIC [OD(nc) u OND] 12 semanas después de concluir la totalidad del tratamiento del estudio.
    (2) Evaluar la seguridad y la tolerabilidad del régimen de combinación de MK 5172, MK 3682 y MK 8742 con o sin Ribavirina para los sujetos de cada grupo.
    E.2.2Secondary objectives of the trial
    (1) To evaluate the efficacy of the combination regimen of MK-5172, MK-3682 and MK-8408 + ribavirin as assessed by the proportion of subjects in each arm achieving SVR4 (Sustained Virologic Response 4 weeks after the end of all study therapy)
    (2) Objective: To evaluate the efficacy of the combination regimen of MK-5172, MK-3682 and MK-8408 + ribavirin as assessed by the proportion of subjects in each arm achieving SVR24 (Sustained Virologic Response 24 weeks after the end of all study therapy)
    (3) Objective: Among HIV-1 co-infected patients, to evaluate the proportion of subjects who develop HIV-1 virologic failure (HIV-1 RNA 200 copies/mL, confirmed on two consecutive tests at least 2 weeks apart, in subjects compliant with their HIV antiretroviral therapy
    (4) Objective: Among HIV-1 co-infected patients, to evaluate the effect of the study regimens on CD4 + T-cell counts.
    (1) Evaluar la eficacia del régimen de combinación de MK 5172, MK 3682 y MK8408 con Rivabirina mediante la proporción de sujetos de cada grupo que logren una RVS4 (respuesta virológica sostenida 4 semanas después del final de todo del tratamiento del estudio)
    (2)Evaluar la eficacia del régimen de combinación de MK 5172, MK 3682 y MK8408 con Rivabirina mediante la proporción de sujetos de cada grupo que logren una RVS24 (respuesta virológica sostenida 24 semanas después del final de todo del tratamiento del estudio)
    (3) En pacientes coinfectados por el VIH-1, evaluar la proporción de sujetos que desarrollan fracaso virológico ante VIH 1 (ARN del VIH 1 200 copias/ml, confirmado en dos pruebas consecutivas con al menos 2 semanas de diferencia, en sujetos que cumplen el tratamiento antirretroviral contra el VIH).
    (4) En pacientes coinfectados por el VIH 1, evaluar el efecto de los regímenes del estudio en el recuento de linfocitos T CD4+.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time
    El promotor realizará investigaciones biomédicas en el futuro utilizando las muestras de ADN obtenidas durante este ensayo clínico. Estas investigaciones tendrán por objeto el análisis de biomarcadores para abordar preguntas emergentes que no se describen en otras partes del protocolo (como parte del ensayo principal) y solo se llevarán a cabo en muestras de los pacientes que hayan otorgado el consentimiento correspondiente. El objetivo de la obtención de muestras para investigación biomédica futura consiste en estudiar e identificar biomarcadores que proporcionen información a los científicos sobre las enfermedades y sus tratamientos.
    El objetivo último es utilizar tal información para desarrollar vacunas y fármacos más seguros y eficaces o para garantizar que los pacientes reciban la dosis correcta del fármaco en el momento preciso.
    E.3Principal inclusion criteria
    1.Be > 18 years of age on day of signing informed consent.
    2.HCV RNA (≥10,000 IU/mL in peripheral blood) at the time of screening.
    3.have documented chronic HCV GT1 or HCV GT3 infection (with no evidence of non-typeable or mixed genotype)
    4. have documented relapse, defined as having HCV RNA target not detected at end-oftreatment, but HCV RNA quantifiable (≥LLOQ) during follow-up, after treatment with one of the following direct-acting antiretroviral (DAA) regimens either by approved dosage and duration or by completion of a clinical trial:
    GT1:
    -SOF/LDV ± RBV
    -MK-5172/MK-8742 ± RBV
    GT3:
    -SOF + RBV
    -SOF + PR
    -SOF + DCV ± RBV
    -SOF/LDV ± RBV
    5. be otherwise healthy as determined by the medical history, physical examination, ECG, and clinical laboratory measurements performed at the time of screening
    6. have liver disease staging assessment as follows:
    Absence of cirrhosis is defined as any one of the following:
    -Liver biopsy performed within 24 months of Day 1 of this study showing
    absence of cirrhosis
    -Fibroscan performed within 12 months of Day 1 of this study with a result of
    -12.5 kPa
    -A Fibrosure® (Fibrotest®) score of ≤ 0.48 and Aspartate Aminotransferase to
    Platelet Ratio Index (APRI) of ≤ during Screening
    Compensated cirrhosis is defined as any one of the following:
    -A liver biopsy performed prior to Day 1 of this study showing cirrhosis (F4)
    -Fibroscan performed within 12 calendar months of Day 1 of this study with a
    result >12.5 kPa
    -A FibroSure® (Fibrotest®) performed during Screening with a score of >0.75
    and an aspartate aminotransferase (AST): platelet ratio index (APRI) of >2.
    APRI formula: AST÷lab upper limit of normal (ULN) for AST x 100÷
    (platelet count÷100) (APRI calculation to be provided by the central
    laboratory.)
    7. meet one of the following categories:
    a. The subject is a male who is not of reproductive potential, defined as a male
    who has azoospermia (whether due to having had a vasectomy or due to an
    underlying medical condition).
    b. The subject is a female who is not of reproductive potential, defined as a
    female who either: (1) is postmenopausal (defined as at least 12 months with
    no menses in women ≥45 years of age) and have a documented follicle
    stimulating hormone (FSH) level in the postmenopausal range at pretrial
    (screening); (2) has had a hysterectomy and/or bilateral oophorectomy,
    bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks
    prior to screening; OR (3) has a congenital or acquired condition that prevents
    childbearing.
    c. The subject is a female or a male who is of reproductive potential and agrees
    to avoid becoming pregnant or impregnating a partner beginning at least 2
    weeks prior to administration of the initial dose of study drug, through 6
    months after taking the last dose of study drug (or longer if dictated by local
    regulations), by complying with one of the following: (1) practice
    abstinence† from heterosexual activity OR (2) use (or have their partner use)
    two forms of acceptable contraception during heterosexual activity.
    8. understand the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
    9. provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.

    Refer to protocol for a complete list
    1. Tener una edad mínima de 18 años el día de la firma del consentimiento informado.
    2. Tener una concentración de ARN del VHC (≥10.000 UI/ml en sangre periférica) en el momento de la selección.
    3. Presentar una infección crónica documentada por el VHC de GT1 o GT3 (sin datos de genotipo mixto o no tipificable)
    4. Presentar recidiva documentada, definida como la no detección de ARN del VHC al final del tratamiento, pero con ARN del VHC cuantificable (≥ LIC) durante el seguimiento, tras el tratamiento con una de las siguientes pautas de antirretrovirales de acción directa (AAD), ya sea conforme a la dosis y duración aprobadas o por la finalización de un ensayo clínico:
    GT1:
    -SOF/LDV ± RBV
    -GZR/EBR ± RBV
    GT3:
    -SOF + RBV
    -SOF + PR
    -SOF + DCV ± RBV
    -SOF/LDV ± RBV
    5. Estar, por lo demás, sano, conforme a lo determinado mediante los antecedentes médicos, exploración física, ECG y parámetros analíticos evaluados en el momento de la selección.
    6. Disponer de una de las evaluaciones del estadio de la hepatopatía indicadas a continuación:
    La ausencia de cirrosis se define como cualquiera de las circunstancias siguientes:
    -Biopsia hepática practicada en los 24 meses anteriores al día 1 de este estudio que indique ausencia de cirrosis.
    -Evaluación mediante Fibroscan realizada en los 12 meses anteriores al día 1 de este estudio con un resultado ≤12,5 kPa.
    -Puntuación obtenida en la prueba ®FibroSure (Fibrotest®) ≤0,48 e índice de aspartato aminotransferasa/plaquetas (APRI) ? 1 durante la selección.
    La cirrosis compensada se define como cualquiera de las circunstancias siguientes:
    -Biopsia hepática practicada antes del día 1 de este estudio que indique cirrosis (F4).
    -Evaluación mediante Fibroscan realizada en los 12 meses anteriores al día 1 de este estudio con un resultado > 12,5 kPa.
    -Evaluación mediante FibroSure® (Fibrotest®) realizada durante la selección con una puntuación > 0,75 e índice de aspartato aminotransferasa (AST)/plaquetas (APRI) > 2. Fórmula APRI: AST ÷ límite superior de la normalidad (LSN) del laboratorio para la AST x 100 ÷ {recuento de plaquetas÷100} (el cálculo del APRI será facilitado por el laboratorio central.)
    7.Cumplir una de las condiciones siguientes:
    a. El sujeto es un varón sin capacidad reproductiva, definido como todo aquel con azoospermia (ya sea por haberse sometido a vasectomía o por un trastorno médico subyacente).
    b. El sujeto es una mujer sin capacidad reproductiva, definida como toda aquella que: (1) es posmenopáusica (es decir, ausencia de menstruación durante al menos 12 meses en mujeres de edad ≥45 años) y presenta una concentración documentada de folitropina (FSH) en el intervalo posmenopáusico antes del ensayo (en la selección), (2) se ha sometido a una histerectomía u ovariectomía bilateral, salpingectomía bilateral o ligadura/oclusión de trompas bilateral al menos 6 semanas antes de la selección O (3) presenta un trastorno congénito o adquirido que impide la concepción.
    c. El sujeto es una mujer o un varón con capacidad reproductiva que se compromete a evitar quedarse embarazada o a dejar embarazada a su pareja desde al menos dos semanas antes de administrar la primera dosis del fármaco del estudio y hasta seis meses después de recibir la última dosis del fármaco del estudio (o más tiempo cuando así lo establezca la normativa local), cumpliendo para ello alguna de las medidas siguientes: (1) practicar abstinencia† de relaciones heterosexuales O (2) utilizar (o hacer que su pareja utilice) al menos dos métodos anticonceptivos aceptables durante las relaciones heterosexuales.
    8. Comprender los procedimientos del estudio, los tratamientos alternativos disponibles y los riesgos que entraña el estudio y aceptar voluntariamente participar otorgando su consentimiento informado por escrito.
    9. Otorgar el consentimiento informado por escrito para el ensayo. Podrán otorgar también su consentimiento para investigaciones biomédicas futuras. No obstante, podrán participar en el ensayo principal sin necesidad de hacerlo en las investigaciones biomédicas futuras.

    Consulte el protocolo para la lista completa
    E.4Principal exclusion criteria
    1. is under the age of legal consent, is mentally or legally incapacitated, has significant emotional problems at the time of pre-study screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, would interfere with the study procedures .
    2. has previously received a DAA containing regimen other than the permitted regimens listed in Inclusion Criterion nº4. Examples of exclusionary regimens include, but are not limited to:
    -SOF + PR or SOF + RBV for GT1
    -SIM + SOF ± RBV
    -OBV/PTV/r and DSV ± RBV
    3. did not complete their prior DAA therapy due to intolerance to the DAA regimen or who discontinued the DAA regimen for reasons other than virologic failure (e.g., non-compliance, lost to follow-up, withdrew consent).
    NOTE: The trial is limited to those who have documented virologic relapse with a properly administered DAA regimen.
    4. has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease.
    5. For cirrhotics, subjects that are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >6, must be excluded. NOTE: To calculate the Child-Pugh score, refer to the following website: http://www.mdcalc.com/child-pugh-score-for-cirrhosis-mortality.
    6. is coinfected with hepatitis B virus (e.g. HBsAg positive).
    7. For subjects with HIV, has a history of opportunistic infection in the preceding 6 months prior to screening. A list of these events may be found in Appendix B of the following document: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm
    8. has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy.
    9. has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of
    hepatocellular carcinoma (HCC) or is under evaluation for HCC.
    NOTE: If liver imaging within 6 months of Day 1 is not available, imaging is
    required during screening.
    10. is taking or plans to take any of the prohibited medications listed in the protocol or is taking herbal supplements, including but not limited to St. John´s Wort (Hypericum perforatum) from 2 weeks prior to Day 1 through 2 weeks after the study treatment period.
    11. Is currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study. (Subjects participating in MK-5172 Protocol 017 may be enrolled in this study, MK- 3682 Protocol 021).
    12. has clinically-relevant drug or alcohol abuse within 12 months of screening
    13. is a female and is pregnant or breastfeeding or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 through at least 6 months after last dose of study drug, or longer if dictated by local regulations, OR is a male subject who is expecting to donate sperm or planning to impregnate female partner(s) from at least two weeks prior to Day 1 through at least 6 months after last dose of study drug, or longer if dictated by local regulations.
    NOTE: After randomization, those female subjects randomized to a regimen that
    does not contain ribavirin should avoid conceiving or donating eggs and those male subjects randomized to a regimen that does not contain ribavirin should avoid impregnating a partner or donating sperm for at least 14 days after taking the last dose of study drug.
    14. is a male whose female partner(s) is/are pregnant.
    Refer to protocol for a complete list of exclusion criteria
    1. No tienen la edad de consentimiento legal, están incapacitados mental o legalmente, presentan problemas emocionales importantes en el momento de la visita de selección previa al estudio o pueden tenerlos previsiblemente durante la realización del estudio, o tienen antecedentes de un trastorno psiquiátrico clínicamente importante que, en opinión del investigador, podría interferir en los procedimientos del estudio.
    2. Han recibido previamente un tratamiento AAD distinto de los permitidos e indicados en el criterio de inclusión n.º 4. Algunos ejemplos de tratamiento que serán motivo de exclusión son, entre otros, los siguientes:
    -SOF + PR o SOF + RBV para tratar el GT1.
    -SIM + SOF ± RBV.
    -OBV/PTV/r y DSV ± RBV.
    3. No completaron el tratamiento AAD previo por intolerancia del tratamiento AAD o no han tenido respuesta al tratamiento AAD por motivos distintos de la recidiva (por ejemplo, recaída virológica, rebote o falta de respuesta, incumplimiento, pérdida para el seguimiento, retirada del consentimiento).
    NOTA: El ensayo se encuentra limitado a sujetos con recidiva después del tratamiento con una pauta AAD correctamente administrada.
    4. Presentan indicios de hepatopatía descompensada, manifestada por la presencia o los antecedentes de ascitis, hemorragia por varices esofágicas o gástricas, encefalopatía hepática u otros signos o síntomas de hepatopatía avanzada.
    5. For cirrhotics, subjects that are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >6, must be excluded. NOTE: To calculate the Child-Pugh score, refer to the following website: http://www.mdcalc.com/child-pugh-score-for-cirrhosismortality.
    6. Presentan una infección simultánea por el virus de la hepatitis B (por ejemplo, HBsAg positivo).
    7. En los sujetos infectados por el VIH, antecedentes de infección oportunista en los 6 meses anteriores a la selección. Se puede consultar una lista de estos episodios en el apéndice B del siguiente documento: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm.
    8. Tienen antecedentes de neoplasias malignas ≤5 años antes de firmar el consentimiento informado, salvo carcinoma basocelular o espinocelular de piel o cáncer in situ de cuello uterino debidamente tratado o carcinoma in situ, o se encuentran en evaluación por otra neoplasia maligna activa o presunta.
    9. Presentan cirrosis y cuentan con estudios de imagen realizados en los 6 meses previos al día 1 con datos de carcinoma hepatocelular (CHC) o se encuentran en evaluación por CHC.
    NOTA: Cuando no se disponga de un estudio de imagen del hígado realizado en los 6 meses previos al día 1, tendrá que realizarse uno durante la selección.
    10. Están tomando o tienen previsto tomar alguno de los medicamentos prohibidos indicados en este protocolo o están tomando suplementos de herbolario, como por ejemplo hipérico (Hypericum perforatum), desde 2 semanas antes del día 1 hasta 2 semanas después del período de tratamiento del estudio.
    11. Están participando o han participado en un estudio sobre un compuesto experimental en los 30 días previos a la firma del consentimiento informado y no están dispuestos a abstenerse de participar en otro estudio durante el transcurso de este estudio. (Los sujetos que estén participando en el protocolo 017 de MK-5172 podrán participar en este estudio, el protocolo 021 de MK-3682).
    12. Presentan un consumo excesivo y clínicamente importante de drogas o alcohol en los 12 meses previos a la selección.
    13. El sujeto es una mujer embarazada o en período de lactancia o tiene previsto concebir o donar óvulos desde al menos 2 semanas antes del día 1 hasta al menos 6 meses después de la última dosis del fármaco del estudio, o más tiempo cuando así lo establezca la normativa local, O es un varón que tiene previsto donar semen o dejar embarazada a su pareja desde al menos dos semanas antes del día 1 hasta al menos 6 meses después de la última dosis del fármaco del estudio, o más tiempo cuando así lo establezca la normativa local.
    NOTA: Después de la aleatorización, las mujeres aleatorizadas a recibir una pauta que no contenga ribavirina deberán evitar quedarse embarazadas o donar óvulos y los varones aleatorizados a recibir una pauta que no contenga ribavirina deberán evitar dejar embarazada a su pareja y donar semen durante al menos 14 días después de tomar la última dosis del fármaco del estudio.
    14. Son varones y su pareja está embarazada.
    Consulte el protocolo para la lista completa
    E.5 End points
    E.5.1Primary end point(s)
    1) Proportion of subjects achieving SVR12.
    La proporción de sujetos que logren una RVS12
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 weeks after the end of treatment
    12 semanas después de concluir el tratamiento.
    E.5.2Secondary end point(s)
    1) The proportion of subjects achieving SVR4
    2) The proportion of subjects achieving SVR24.
    3) The proportion of subjects who develop HIV-1 virologic failure during protocol therapy for HIV co-infected population;
    4) Change from baseline in CD4+ T-cell counts for HIV co-infected population.
    1) La proporción de sujetos que logren una RVS4
    2) La proporción de sujetos que logren una RVS24
    3) 2La proporción de sujetos que desarrollen fracaso virológico del VIH 1 durante el tratamiento por protocolo de la población coinfectada por el VIH
    4) La variación del recuento de linfocitos CD4+ respecto al valor basal en la población coinfectada por el VIH
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) 4 weeks after the end of treatment 2) 24 weeks after the end of treatment
    2) 2) 24 weeks after the end of treatment
    1) 4 semanas después de concluir el tratamiento.
    2) 24 semanas después de concluir el tratamiento.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    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.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA19
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    France
    Germany
    Spain
    Sweden
    United Kingdom
    United States
    E.8.7Trial 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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days21
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days21
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 180
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 97
    F.4.2.2In the whole clinical trial 200
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    Ninguno
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-12-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-11-23
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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