Chronic Hepatitis C Virus Infection (Genotypes 1 and 4) in Treatment-Naive Subjects MedDRA version: 9.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C
Conditions
Interventions
Product Name: HCV NS3 Protease Inhibitor
Product Code: BMS-650032-01
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: BMS-650032-01
Other descriptive name: HCV NS3 Protease Inhibitor
Conc
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent a) Freely given informed consent must be obtained from subjects prior to clinical trial participation, including informed consent for any screening procedures conducted to establish subject eligibility for the study. 2) Target Population a) Subjects chronically infected with HCV genotype 1 as documented by: positive for anti-HCV antibody, HCV RNA, or a positive HCV genotype test at least 6 months prior to screening, and positive for HCV RNA and anti-HCV anti-body at the time of screening (Stages 1 and 2); b) Subjects chronically infected with HCV genotype 4 as documented by: positive for anti-HCV antibody, HCV RNA, or a positive HCV genotype test at least 6 months prior to screening, and positive for HCV RNA and anti-HCV anti-body at the time of screening (Stage 2 only); c) HCV RNA viral load of = 100,000 IU/mL at screening; d) Results of a biopsy obtained = 24 months prior to randomization showing no evidence of cirrhosis (Stage 1 only); e) Body Mass Index (BMI) of 18 to 35 kg/m², inclusive. BMI = weight (kg)/[height (m)]² at screening 3) Age and Sex a) Men and women, ages 18 to 70; b) Women of childbearing potential (WOCBP), unless non-heterosexual active or who have vasectomized male partners, and sexually active men (unless vasectomized) with female partners who are WOCBP must use two separate forms of contraception, one of which must be an effective barrier method (eg, condom with spermicide), from screening throughout the duration of the study and for 24 weeks after the last dose of ribavirin. In addition, WOCBP must agree to the pregnancy testing schedule specified in this protocol. Oral contraceptive pills (OCPs) may be used in this study, but cannot be considered one of the two effective forms of contraception required because drug interaction studies verifying the effectiveness of OCPs when used with BMS-650032 have not been completed. Men (unless vasectomized) with female partners who are WOCBP must agree to inform their female partners of the protocol-specified contraception requirements and pregnancy testing recommendations during treatment and post-treatment (monthly pregnancy testing on-treatment and following discontinuation of RBV for 6 months post-treatment or the duration specified in the label used for RBV in that country), and agree to adhere to these recommendations for both the on-treatment and post-treatment follow-up period. WOCBP are defined as a non-menopausal female or a female with menopause = 2 years and who has not had a hysterectomy, bilateral tubal ligation, bilateral oophorectomy or medically documented ovarian failure. Female subjects who are postmenopausal for less than two years are required to have FSH > 40 mIU/mL. If the FSH is = 40 mIU/mL, the subject must agree to use two forms of contraception to participate in the study. 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 > 40 mIU/mL. Non-menopausal women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermici
Exclusion criteria
Exclusion criteria: 1)Sex and Reproductive Status a)WOCBP unwilling or unable to use an acceptable method to avoid pregnancy (two effective forms of contraception) for the entire study period (on treatment) and for up to 24 weeks after the last dose of investigational product b)Women who are pregnant of breastfeeding c)Women with positive pregnancy test on enrollment or prior to investigational product administration 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 (contraindicated with RBV use) 2)Medical History and Concurrent Diseases a)Evidence of medical condition associated with chronic liver disease other than HCV b)Evidence of decompensated cirrhosis based on radiologic criteria or biopsy results and clinical criteria (in Stage 2) (Note: Subjects with compensated cirrhosis may be enrolled in Stage 2) c)Evidence of HCC documented by ultrasound (U/S), computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 12 months of randomization d)Co-infection with HBV, HIV-1 or HIV-2 at screening e)History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis f)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 g)Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug; h)Any other medical, psychiatric and/or social reason including active substance or alcohol abuse, as defined by DMS IV, Diagnostic Criteria for Drug and Alcohol Abuse (see Protocol Appendix 3), which in the opinion of the investigator, would make the candidate inappropriate for participation in this study i)Inability to tolerate oral medication j)Poor venous access k)Liver transplant recipients 3)Physical & Laboratory Test Findings a)ALT =5 x ULN b)Total bilirubin =2 mg/dL (or = 34 µmol/L) c)INR= 1.7 d)Albumin =3.5 g/dL (35 g/L) e)Creatinine clearance (CrCl) (as estimated by Cockcroft and Gault) =50 mL/min f)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) g)Positive HBs Antigen 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 pegIFNa and RBV package inserts. a)Severe psychiatric disease, especially untreated or unstable depression, that would prohibit use of pegIFNa as judged by the 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 signif
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Both Stage 1 and Stage 2 primary objectives will be based on their respective Week 12 analysis of safety and antiviral activity data. In addition, a co-primary objective of Stage 2 will be based on follow-up anti-viral activity data (SVR). The Week 12 analysis in Stage 1 supports dose selection decisions for Stage 2 while the analyses in Stage 2 will support the overall HCV program (add-on to SOC and combination anti-viral studies) and inform decisions on both dose (Week 12 analysis) and duration (SVR analysis).;Secondary Objective: • To assess the proportion of HCV genotype 1 subjects with rapid virologic response (RVR), defined as undetectable HCV RNA at Week 4; • To assess the proportion of HCV genotype 1 subjects with early virologic response (EVR), defined as = 2 log10 decrease in HCV RNA from baseline at Week 12 (or undetectable HCV RNA for subjects with baseline HCV RNA < 1000 IU/mL); • To assess the proportion of HCV genotype 1 subjects with 12-week sustained virologic response (SVR12), defined as undetectable HCV RNA at follow-up Week 12; • To describe resistant variants associated with virologic failure;Primary end point(s): • Safety, as measured by the frequency of SAEs and discontinuations due to AEs; • Antiviral activity, as determined by the proportion of HCV genotype 1 subjects with extended rapid virologic response (eRVR), defined as undetectable HCV RNA at both Weeks 4 and 12; • Antiviral activity, as determined by the proportion of HCV genotype 1 subjects with 24-week sustained virologic response (SVR24), defined undetectable HCV RNA at follow-up Week 24 (Stage 2 only). | — |
Countries
France, Germany, Ireland, Italy, Spain, United Kingdom
Outcome results
None listed