Chronic Genotype 2 or 3 HCV Infection MedDRA version: 14.1 Level: LLT Classification code 10019752 Term: Hepatitis C virus (HCV) System Organ Class: 10022891 - Investigations
Conditions
Sponsors
Gilead Sciences Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Males or females at least 18 years old, or the legal age of consent, whichever is older, at Screening. Subjects or their heterosexual partner(s) must either be of non-childbearing potential or they must use effective contraception from 2 weeks before the initiation of therapy until 6 months (or the duration recommended locally for ribavirin if longer) after the last dose of study medication. 2) Chronic Genotype 2 or 3 HCV-infection documented by at least one measurement of serum HCV RNA = 10,000 IU/mL 3) Patients with Childs A cirrhosis may be included (up to 20% of patients randomized) 4) Subjects must be naïve to all HCV antiviral treatment(s), including but not limited to immunomodulatory and nucleoside/tide treatments for chronic HCV infection. 5) A body mass index (BMI) of =18kg/m2 6) Otherwise suitable for participation as determined by the medical history, physical examination, ECG, and clinical laboratory measurements performed at Screening 7) Able to effectively communicate with the Investigator and other center personnel. Willing to give written informed consent and comply with the study restrictions and requirements Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 450 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1) Positive test at Screening for HBsAg, anti-HBc IgM Ab, or anti-HIV Ab. 2) History of any other clinically significant chronic liver disease. 3) A history of consistent with decompensated liver disease including ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome and hepatopulmonary syndrome, among others. 4) History or current evidence of psychiatric illness, immunologic disorder, hemoglobinopathy, pulmonary disease (including pneumonia or pneumonitis), cardiac disease, seizure disorder or anticonvulsant use, poorly controlled diabetes, cancer, or a history of malignancy that in the opinion of the investigator makes the patient unsuitable for the study. Chronic medical conditions, especially if treated with medications (such as hypertension), must be stable at the time of screening. No new therapies should be started prior to the study that may confound the assessment of study drug safety. 5) Clinical signs and symptoms of acute pancreatitis with elevated lipase 6) Clinically significant ECG findings at screening, screening QTc = 450 ms (non-cirrhotic) or = 500 ms (cirrhotic), or a personal or family history of Torsades de pointes. 7) History of major organ transplantation with an existing functional graft. 8) Active substance abuse which, in the opinion of the investigator, would make the candidate inappropriate for participation in this study. 9) History of uncontrolled thyroid disease or abnormal TSH levels as defined 1.2 x ULN at Screening (subjects will be eligible with an abnormal TSH if the T3 and T4 are within normal limits). 10) Abnormal haematological and biochemical parameters. 11) Donation or loss of more than 400 mL blood within 2 months prior to first dose administration. 12) History of clinically significant drug allergy to nucleoside/nucleotide analogs. 13) History of having received any systemic antineoplastic or radiation therapy within 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study. 14) Subjects receiving oral or intravenous strong p-glycoprotein inhibitors (including cyclosporine, quinidine, dronedarone, itraconazole, verapamil or ritonavir) within 28 days of dosing. Additional concomitant medications disallowed in this study are outlined in Table 14 of the protocol. 15) Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to first dose administration. 16) Pregnant/Breastfeeding women or males whose partners are currently pregnant. 17) Poor venous access making the patient unable to complete the required laboratory testing schedule.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of PSI-7977 in combination with RBV administered for 12 weeks compared with PEG/RBV administered for 24 weeks in treatment-naïve patients with HCV genotype 2 or 3 as assessed by the rate of SVR12 (HCV RNA <LOQ 12 weeks after cessation of therapy);Secondary Objective: 1) To assess the safety and tolerability of PSI-7977/RBV administered for 12 weeks as measured by the frequency of deaths, serious adverse events (SAEs), discontinuations due to AEs, and Grade 3 or 4 laboratory abnormalities 2) To determine the SVR at Week 24 (SVR24) following completion of treatment for each investigational arm (HCV RNA <LOQ 24 and 48 weeks after cessation of therapy) 3) To evaluate the change in circulating HCV RNA in patients over 12 or 24 weeks of dosing 4) To determine the proportion of patients with HCV RNA below the lower limit of quantitation (LOQ) and lower limit of detection (LOD) at various time points thoughout the study 5) To determine the proportion of patients whose ALT normalizes during therapy 6) To describe rates of virologic failure 7) To characterize HCV drug resistance substititions at baseline, during, and after therapy with PSI-7977;Primary end point(s): The primary efficacy endpoint is sustained viral response 12 weeks post last dose of any treatment (HCV RNA <LOQ 12 weeks after cessation of therapy) in the ITT population (SVR12).;Timepoint(s) of evaluation of this end point: 12 weeks post last treatment dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Safety: Adverse events (AE), safety labs, electrocardiograms (ECGs) and vital signs. 2) Sustained viral response 24 weeks post last dose of any treatment (HCV RNA <LOQ 24 weeks after cessation of therapy) in the ITT population (SVR24). ;Timepoint(s) of evaluation of this end point: Safety and tolerability will be assessed throughout the study. SVR24 will be assessed 24 weeks post the last treatment dose. | — |
Countries
Australia, Canada, Estonia, Italy, Netherlands, New Zealand, Puerto Rico, Spain, Sweden, United States
Contacts
Public ContactMedical Monitor
Gilead Sciences Inc
Outcome results
None listed