E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 14.0 |
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 |
Offer patients with virological failure in the placebo controls of the Phase III trials 1220.7, 1220.30 and 1220.47 open label treatment with BI 201335, PegIFN and RBV. |
Ofrecer a los pacientes con fracaso virológico de los grupos controles con placebo de los ensayos de fase III 1220.7, 1220.30 y 1220.47 la posibilidad de recibir tratamiento en abierto con BI 201335, PegIFN y RBV. |
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E.2.2 | Secondary objectives of the trial |
To collect additional evidence for the safety of 24 weeks of treatment with BI 201335 240 mg once daily in combination with 48 of PegIFN and RBV in HCV genotype 1 infected treatment-experienced patients. |
Recoger datos adicionales sobre la seguridad de 24 semanas de tratamiento con BI 201335 240 mg una vez al día en combinación con 48 semanas de PegIFN y RBV en pacientes con infección por el VHC de genotipo 1 y experiencia previa de tratamiento. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients from trials 1220.7, 1220.30 and 1220.47 of BI 201335 who have failed treatment with PegIFN/RBV in the placebo groups due to protocol-defined criteria of treatment failure (i.e. either non-response on treatment or relapse after end of treatment [EOT]). 2. Patients must have received at least 4 weeks of assigned trial medication and been compliant with all study procedures. 3. Female patients: a) with documented hysterectomy, b) who have had both ovaries removed, c) with documented tubal ligation, d) who are post-menopausal with last menstrual period at least 12 months prior to screening, or e) of childbearing potential with a negative serum pregnancy test at screening and Day 1, that, if sexually active, agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of RBV in addition to the consistent and correct use of a condom. Patients must agree not to breast-feed at any time from the date of screening until 7 months after the last dose of RBV. f) Medically accepted methods of contraception for females in this trial are ethinyl estradiol-containing contraceptives, diaphragm with spermicide substance, intra-uterine device and cervical cap. Male patients: a) who are documented to be sterile, or b) who are without pregnant female partner(s) and consistently and correctly use a condom while their female partner(s) (if of child-bearing potential) agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin. It is in the responsibility of the male patient to ensure that his partner(s) is not pregnant prior to screening into the study or becomes pregnant during the treatment and the observation phase. Female partners of childbearing potential must perform monthly pregnancy tests from the date of screening until 7 months after the last dose of ribavirin (tests will be provided by the sponsor). 4. Signed informed consent form prior to trial participation. |
. Pacientes de los ensayos 1220.7, 1220.30 y 1220.47 de BI 201335 en los que ha fracasado el tratamiento con PegIFN/RBV en los grupos placebo conforme a los criterios de fracaso del tratamiento definidos en el protocolo (es decir, sin respuesta durante el tratamiento o recidiva después del final del tratamiento [EOT]). 2. Los pacientes deben haber recibido al menos 4 semanas de la medicación del ensayo asignada y haber cumplido todos los procedimientos del estudio. 3. Mujeres: - con histerectomía demostrada, - con doble ovariectomía, - con ligadura de trompas demostrada, - que son posmenopáusicas con un período desde la última menstruación de al menos 12 meses antes de la selección, o - en edad fértil con prueba de embarazo en suero negativa durante el proceso de selección y en el día 1, que, si son sexualmente activas, aceptan utilizar uno de los métodos anticonceptivos médicamente aceptables adecuados desde la fecha de la selección hasta 7 meses después de la última dosis de ribavirina, además del uso sistemático y correcto de un preservativo. Las pacientes deben estar de acuerdo en no dar el pecho en ningún momento desde la fecha de la selección hasta 7 meses después de la última dosis de ribavirina. - Los métodos de anticoncepción médicamente aceptados para las mujeres en este estudio son los anticonceptivos que contengan etinilestradiol, diafragma con sustancia espermicida, dispositivo intrauterino y capuchón cervical. Hombres: - que demuestren ser estériles, o - que no tienen una pareja femenina embarazada y que utilicen sistemática y correctamente un preservativo mientras su pareja (o parejas) (si están en edad fértil) acepte utilizar un método anticonceptivo médicamente aceptable adecuado desde la fecha de la selección hasta 7 meses después de la última dosis de ribavirina. El varón es responsable de asegurarse de que su pareja (o parejas) no está embarazada antes del proceso de selección en el estudio ni se queda embarazada durante las fases de tratamiento y observación. Las parejas femeninas en edad fértil deberán realizar una prueba de embarazo mensual desde la fecha de la selección hasta 7 meses después de la última dosis de ribavirina (el promotor suministrará las pruebas).
4. Documento de consentimiento informado firmado antes de participar en el estudio |
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E.4 | Principal exclusion criteria |
1. Evidence of acute or chronic liver disease due to causes other than chronic HCV infection. 2. HIV co-infection. 3. Hepatitis B virus (HBV) infection based on presence of HBs-Ag. 4. Active malignancy, or history of malignancy within the last 5 years prior to screening (with an exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix). 5. Active or, history of alcohol or illicit drug abuse other than cannabis within the past 12 months. 6. A condition that is defined as one which in the opinion of investigator may put the patient at risk because of participation in this study, may influence the results of this study, or limit the patient’s ability to participate in this study. 7. Usage of any investigational drugs within 30 days prior to screening, or planned usage of an investigational drug during the course of this study. 8. Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 30 days prior to screening. Patients being treated with oral antivirals such as acyclovir, famiclovir or valacyclovir for recurrent herpes simplex infection; or with oseltamivir or zanamivir for influenza A infection, may be screened. 9. Received silymarin (milk thistle), glycyrrhizin, or Sho-saiko-to (SST) within 28 days prior to screening. 10. Patients who have been previously treated with at least one dose of any antiviral or immunomodulatory drug other than interferon alfa or ribavirin for acute or chronic HCV infection including and not restricted to protease or polymerase inhibitors. 11. Known hypersensitivity to any ingredient of the study drugs. 12. Alpha fetoprotein value > 100 ng/mL at screening; if > 20 ng/mL and ≤ 100 ng/mL, patients may be included if there is no evidence of liver cancer in an appropriate imaging study (e.g., ultrasound, CT scan, or Magnetic Resonance Imaging [MRI] within last six months prior to randomization (Visit 2). 13. Decompensated liver disease, or history of decompensated liver disease, as defined by the presence of: hepatic encephalopathy, ascites, or esophageal variceal bleeding, and/or any laboratory results of any of the following: -. International normalized ratio (INR) of ≥ 1.7. -. Serum Albumin ≤ 3.5 g/dL. -. Serum total bilirubin ≥ 2.0 mg/dL (except when the increase is predominately due to unconjugated bilirubin related to Gilbert’s syndrome). 14. Pre-existing psychiatric condition that could interfere with the subject’s participation in and completion of the study including but not limited to prior suicidal attempt, schizophrenia, major depression syndrome, severe anxiety, severe personality disorder, a period of disability or impairment due to a psychiatric disease within the past five years. 15. Clinical evidence of significant or unstable cardiovascular disease, including angina, myocardial infarction within six months, pulmonary hypertension, cardiomyopathy, congestive heart failure, uncontrolled hypertension, significant arrhythmia or clinically significant abnormalities on ECG at screening. 16. Clinical evidence of chronic pulmonary disease (e.g. chronic obstructive pulmonary disease) associated with functional impairment. 17. Active autoimmune disease, including autoimmune hepatitis. 18. History or evidence of retinopathy or clinically significant ophthalmological disorder including diabetic or hypertensive retinopathy, retinal haemorrhages, cotton wool spots, papilloedema, optic neuropathy, or retinal artery/vein obstruction. An eye examination performed within 6 months prior to randomization (Visit 2) is required. 19. Organ transplant history other than cornea or hair. 20. Require chronic systemic corticosteroids (nasal or pulmonary steroids will be allowed). 21. Active seizure disorder within the last 2 years (Note: Patients may be enrolled if on stable medication and without seizures for more than 2 years prior to screening). 22. Red blood cell disorders which include but are not limited to thalassemia major, sickle cell anemia or G6PD deficit. Patients with traits or minor diseases (e.g. sickle cell trait or thalassemia minor) may be enrolled if the disease does not result in anemia, according to the investigator’s clinical judgment. 23. Body weight < 40 or > 125 kg. 24. Hemoglobin < 12 g/dL for women and < 13 g/dL for men. 25. Poorly controlled diabetes mellitus, defined as HbA1c ≥ 8.5%. 26. White blood cell count < 2,000 cells/mm3 27. Absolute neutrophil count < 1,500 cells/mm3 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Sustained Virological Response (SVR): Plasma HCV RNA level < 25 IU/mL, undetected 24 weeks after the originally planned treatment duration |
Respuesta virológica mantenida (SVR): HCV-RNA < 25 UI/ml en plasma indetectable a las 24 semanas después de la duración del tratamiento prevista originalmente. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
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 | Information not present in EudraCT |
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.8.3 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 110 |
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 |
Austria |
Belgium |
France |
Germany |
Japan |
Korea, Republic of |
Portugal |
Romania |
Russian Federation |
Spain |
Switzerland |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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Last visit of last subject undergoing the trial |
Última visita del último paciente del ensayo. |
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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 | 3 |
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 |