Chronic Hepatitis C Virus Genotype 1 Infection in Treatment Naïve Subjects MedDRA version: 9.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C
Conditions
Interventions
Product Code: BMS-790052-05
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: BMS-790052-05
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceu
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent 2) Target Population a) Subjects chronically infected with HCV genotype 1; b) HCV RNA viral load of = 10(5) IU/mL (100,000 IU/mL) at screening; c) Less than 4 weeks of total therapy with either IFN, pegIFNa, or RBV at any time and with no exposure to IFN, pegIFNa or RBV in the 24 weeks prior to randomization; d) Results of a biopsy obtained = 24 months prior to randomization; e) No evidence of cirrhosis based on liver biopsy or clinical criteria; f) No evidence of HCC documented by ultrasound (U/S), computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 12 months of randomization; g) Absence of co-infection with hepatitis B virus (HBV), HIV-1 or HIV-2 at screening; h) Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2 at screening. 3) Age and Sex a) Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) and men, ages 18 to 70; Women are considered surgically sterile only if they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy. Post menopause is defined as: • Amenorrhea = 12 consecutive months without another cause or • For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Sex and Reproductive Status a) Women of Childbearing Potential (WOCBP) b) Women who are pregnant or breastfeeding; c) Women with a positive pregnancy test on enrollment or prior to administration of investigational product; d) Sexually active fertile men not using effective birth control if their partners are WOCBP; e) Sexually active fertile men whose partners are pregnant at screening are excluded from this study (a contraindication for RBV use). 2) Medical History and Concurrent Diseases a) Evidence of a medical condition associated with chronic liver disease other than HCV (such as but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures); b) History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis; c) Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment; d) Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug; e) Any other medical, psychiatric and/or social reason which, in the opinion of the investigator, would make the candidate inappropriate for participation in this study; f) Inability to tolerate oral medication; g) Poor venous access. 3) Physical and Laboratory Test Findings at Screening a) ALT = 5 × ULN; b) Total bilirubin = 34 µmol/L (or = 2 mg/dL); c) INR = 1.7; d) Albumin = 3.5 g/dL (35 g/L); e) Any ECG finding which in the opinion of the investigator, would make the candidate inappropriate for participation in this study (ie corrected QT value > 450 msec, second/third degree bundle branch block). 4) Medical History or Laboratory Findings that Exclude Subject from pegIFNa or RBV Therapy: The following exclusion criteria are based on guidelines or recommendations from the pegIFNa22 and RBV23 package inserts. a) Severe psychiatric disease, especially untreated or unstable depression, that would prohibit use of pegIFNa as judged by investigator; b) History of hemoglobinopathies (ie, thalassemia major or sickle cell anemia), diagnoses associated with an increased baseline risk for anemia (eg, spherocytosis), hemolytic anemia, or diseases in which anemia would be medically problematic; c) History of thyroid dysfunction not adequately controlled or screening thyroid function tests that indicate abnormal thyroid function; d) History of chronic pulmonary disease associated with functional limitation; e) History of cardiomyopathy, coronary artery disease (including angina), interventive procedure for coronary artery disease (including angioplasty, stent procedure, or cardiac bypass surgery), ventricular arrhythmia, or other clinically significant cardiac disease; f) Pre-existing ophthalmologic disorders considered clinically significant on eye or retinal exam (all subjects with history of diabetes or hypertension must have a documented eye exam within 12 months prior to randomization); g) Platelets = 90 × 109 cells/L; h) ANC = 1.5 × 109 cells/L; i) Hemoglobin = 12 g/dL (120 g/L) for women and = 13 g/dL (130 g/L) for men; j) Creatinine clearance (CrCl) as (as estimated by Cockcroft and Gault) = 50 mL/min; k) Any known contraindication to pegIFNa or RBV, not otherwise specified. 5) Allergies and Adverse Drug Reactions a) History of hypersensitivity to drugs with a similar biochemical structure to BMS-790052, pegIFNa, or RBV. 6) Prohi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To describe: • Safety, as measured by the frequency of SAEs, discontinuations due to AEs, and Grade 3 - 4 laboratory abnormalities and, • Antiviral activity as determined by the proportion of subjects with extended rapid virologic response (eRVR) defined as HCV RNA < 10 IU/mL at both Weeks 4 and 12.;Secondary Objective: To describe: • Proportion of subjects with rapid virologic response (RVR), defined as HCV RNA < 10 IU/mL at Week 4; • Proportion of subjects with early virologic response (EVR), defined as = 2 log(10) decrease in HCV RNA from baseline at Week 12 (or HCV RNA < 10 IU/mL for subjects with baseline HCV RNA < 1000 IU/mL); • Proportion of subjects with a sustained virologic response (SVR), defined as HCV RNA < 10 IU/mL at follow-up Week 12 (SVR12) and Week 24 (SVR24), respectively. Additional exploratory objectives: • Identification and quantitation of resistant variants associated with clinical failure; • Relationship between measures of safety or antiviral activity and exposure to BMS-790052 when co-administered with pegIFNa/RBV; • To describe the pharmacokinetics of BMS-790052, RBV, and PegIFNa; • To explore the effect of BMS-790052 on expression of IFN stimulated genes (ISGs) when co-administered with PegIFNa and RBV.;Primary end point(s): • Safety, as measured by the frequency of SAEs, discontinuations due to AEs, and Grade 3 - 4 laboratory abnormalities and, • Antiviral activity as determined by the proportion of subjects with eRVR | — |
Countries
France
Outcome results
None listed