Chronic Hepatitis C MedDRA version: 14.1 Level: PT Classification code 10008912 Term: Chronic hepatitis C System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: NS5A Replication Co-Factor Inhibitor
Product Code: BMS-790052-05
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Daclatasvir
Current Sponsor code: BMS-790052-05
Concentratio
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) Failure of prior pegIFNa/RBVtherapy as defined in Section 3.3.4; c) HCV RNA viral load of = 100,000 IU/mL at screening; d) Results of liver biopsy obtained = 24 months prior to randomization consistent with chronic HCV infection; for compensated cirrhotics, results of liver biopsy documenting cirrhosis can be from any time period prior to randomization (Compensated cirrhotics are capped at 25% of randomized population); e) Ultrasound (U/S), computed tomography (CT) scan, or magnetic resonance imaging (MRI) results 12 months prior to randomization that do not demonstrate evidence of HCC; f) Body Mass Index (BMI) of 18 to 35 kg/m², inclusive. BMI = weight (kg)/[height (m)]² at screening. 3) Age and Reproductive Status a) Men or women, 18 to 70 years of age; b) Contraception requirements: Men and women of childbearing potential must be using 2 separate methods of contraception to avoid pregnancy throughout the study and for up to 24 weeks after the last dose of RBV (or time specified by the country specific RBV label, whichever is longer) in such a manner that the risk of pregnancy is minimized. See Section 3.3.3 for definition of WOCBP. One (1) form of contraception must be effective barrier method (eg, condom, diaphragm, cervical cap). Oral contraceptive pills (OCPs) may be used in this study as one of the two effective forms of contraception based on results of a drug interaction study with BMS-790052 and Ortho Tri-Cyclen. This contraception requirement applies in all cases of heterosexual intercourse in which the female partner is a WOCBP, except when the male partner is vasectomized for a minimum of 6 months; c) Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product. Female subjects must agree to the pregnancy testing requirements in this protocol; d) Women must not be breastfeeding; e) Requirements for male subjects (based on RBV label): i) Male subjects (unless vasectomized for at least 6 months) with female partners who are WOCBP must agree to inform their female partners of the protocol-specified contraception requirement and pregnancy testing recommendations during treatment and post-treatment (ie, 2 forms of contraception and monthly pregnancy testing while the subject is enrolled in the study, and 6 months following discontinuation of RBV or the duration specified in the country-specific RBV label), and agree to adhere to these recommendations both on-treatment and during the post-dosing follow-up period; ii) Male subjects must confirm that their female sexual partners are not pregnant at the time of screening. 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) Target Disease Exceptions a) Infected with HCV other than genotype 1 b) Positive HBsAg, or HIV-1/HIV-2 antibody at screening 2) Medical History and Concurrent Diseases a) Evidence of a medical condition contributing to chronic liver disease other than HCV (such as but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, and toxin exposure) b) Evidence of decompensated cirrhosis based on radiologic criteria or biopsy results and clinical criteria c) Current or known history of cancer within 5 years prior to enrollment (exceptions to this criteria are in situ carcinoma of the cervix or adequately controlled non-melanoma skin cancers) d) Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug e) Any other medical, psychiatric and/or social reason including active substance abuse or alcohol abuse as defined by DSM-IV, Diagnostic Criteria for Drug and Alcohol Abuse (Appendix 1) 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 a) Confirmed ALT = 5 x ULN b) Confirmed total bilirubin = 34 µmol/L (or = 2 mg/dL) c) Confirmed INR = 1.7 d) Confirmed albumin = 3.5 g/dL (35 g/L) e) Confirmed platelets = 90 billion cells/L f) Confirmed ANC = 1.5 billion cells/L g) Confirmed hemoglobin = 12 g/dL (120 g/L) for women and = 13 g/dL (130 g/L) for men h) Confirmed creatinine clearance (CrCl) (as estimated by Cockcroft and Gault) = 50 mL/min i) Patients with a screening QTcF > 450 msec (males) or > 470 msec (females), (three or more ECGs 5 minutes apart while subject is resting in a supine position will be used to establish baseline QTcF) 4) Medical History or Laboratory Findings that Exclude Subjects from Peg-Interferon Alfa-2a or Ribavirin Therapy The following exclusion criteria are based on guidelines or recommendations from the pegIFNa-2a and RBV package inserts: a) Severe psychiatric disease, especially untreated or unstable depression, that would prohibit use of pegIFNa-2a 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 disease in which anemia would be medically problematic c) Thyroid-stimulating hormone (TSH) and/or T4 not within 0.8 to 1.2 times the normal limit, or not adequately controlled thyroid function as assessed by the investigator d) History of chronic pulmonary disease associated with functional limitation e) Unstable or clinically significant cardiovascular disease or hypertension that could be expected to progress, recur or change during study period to such an extent that it could bias the assessment of the clinical status of the patient 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) History of uncontrolled diabetes mellitus h) Any known contraindication to peg-IFNa-2a or ribavirin, not otherwise specified 5) Allergies and Adverse Drug Reaction a) History of hypersensitivity to drugs with a similar biochemical structure to BMS-790052, pegIFNa-2a, or RBV 6) Prohibited Treatments and/or Therapie
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess: • Antiviral activity, as determined by the proportion of subjects with eRVR in each cohort (prior partial responders and prior null responders), defined as undetectable HCV RNA at both Weeks 4 and 12; • Antiviral activity, as determined by the proportion of subjects with SVR24 in each cohort (prior partial responders and prior null responders), defined as undetectable HCV RNA at follow-up Week 24; • Safety, as measured by the frequency of SAEs and discontinuations due to AEs.;Secondary Objective: • To assess the proportion of subjects in each cohort (prior partial responders and prior null responders) with rapid virologic response (RVR), ie, undetectable HCV RNA at Week 4; • To assess the proportion of subjects in each cohort (prior partial responders and prior null responders with complete early virologic response (cEVR), ie, undetectable HCV RNA at Week 12; • To assess the proportion of subjects in each cohort (prior partial responders and prior null responders) with 12-week sustained virologic response (SVR12), ie, undetectable HCV RNA at follow-up Week 12; • To describe resistant variants associated with virologic failure.;Primary end point(s): • Antiviral activity, as determined by the proportion of subjects with eRVR in each cohort (prior partial responders and prior null responders); • Antiviral activity, as determined by the proportion of subjects with SVR24 in each cohort; • Safety, as measured by the frequency of SAEs and discontinuations due to AEs.;Timepoint(s) of evaluation of this end point: • Weeks 4 and 12 • Follow-up Week 24 • on treatment (maximum of 48 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of subjects with rapid virologic response (RVR) • Proportion of subjects with complete early virologic response (cEVR) • Proportion of subjects with SVR12 • Frequency of genotypic substitutions associated with virologic failure;Timepoint(s) of evaluation of this end point: • Week 4 • Week 12 • Follow-up Week 12 • at baseline, on treatment and during follow-up | — |
Countries
Argentina, Australia, Canada, Denmark, France, Germany, Italy, Mexico, Puerto Rico, Sweden, United States
Contacts
Public ContactEU Study Start Up Unit
Bristol-Myers Squibb International Corporation
Outcome results
None listed