sh229 tablets combined with daclatasvir dihydrochloride tablets in treatment adult patients with chronic hepatitis c

Conditions: Hepatitis C, Chronic

Summary: phase ii: exploring the efficacy and safety of different doses of sh229 tablets combined with fixed-dose daclatasvi dihydrochloride (dcv) tablets in the treatment of adult patients with chronic hepatitis c for 12 weeks, providing a basis for the design and implementation of phase iii clinical trials. phase iii: confirmation of the efficacy and safety of sh229 tablets combined with daclatasvi dihydrochloride (dcv) tablets in the treatment of adult patients with chronic hepatitis c for 12 weeks, providing a sufficient basis for drug registration and clinical use.

it is estimated that china has a population of over 10 million infected with hcv and also a highly variable hcv genotype geographic distribution. a simple, universal, non-genotype-specific treatment regimen is preferred for anti-hcv treatment in clinical practice and public health. the combination regimen of sh229 and dcv is expected to completely suppress hcv replication in subjects chronically infected with hcv and achieve a sustained virologic response.

Eligibility criteria:
inclusion criteria: * willing and able to provide written informed consent. * subjects should be able to follow the instructions for the study drug and be able to complete screening, on-treatment, and post treatment assessments. * male or female, age above 18 years * body mass index ( bmi ) between 18 and 32 kg/m2 at screening. * confirmation of chronic hcv infection, which meets one of the following: (a) positive for anti-hcv antibodies, hcv rna or hcv genotyping results within ≤ 6 months of screening, or (b) liver biopsy ≤ 12 months of screening. * hcv rna above 10\^4 iu/ml at screening by the central laboratory. * hcv genotype 1, 2, 4, 5, 6, or indeterminate assessed at screening by the central laboratory. * classification as treatment naïve or treatment experienced (approximately 20% of subjects may be treatment experienced): 1. treatment naïve is defined as having never been exposed to approved or experimental hcv-specific direct-acting antiviral agents ( daa ) or prior treatment of hcv with interferon either with or without rbv. 2. treatment experienced is defined as prior treatment failure to a regimen containing ifn-based antiviral (inf-α, β or peg-ifn ± ribavirin) and met one of the following: (i) non-responder: subject did not achieve undetectable hcv rna levels while ontreatment,, (ii) relapse/breakthrough: subject achieved undetectable hcv rna levels duringtreatment but did not achieve svr, (iii) terminate the treatment , according to associated-hcv therapy adverse events by subject reported or medical records demonstrated. * cirrhosis determination (approximately 20% of subjects may have cirrhosis)： 1. cirrhosis is defined as any one of the following: (i) fibroscan with a result of \>12.5 kpa within ≤ 6 months of screening, (ii) liver biopsy showing cirrhosis within ≤ 12 months of screening. 2. absence of cirrhosis is defined as any one of the following:(i) fibroscan with a result of ≤ 12.5 kpa within ≤ 6 months of screening, (ii) liver biopsy showing non-cirrhosis within ≤ 12 months of screening. exclusion criteria: * exposure nucleotide analogue including hcv ns3-4a inhibitor, hcv ns5b inhibitor or any hcv ns5a inhibitor before baseline/day 1. * receive ifn-based antiviral therapy within 6 months prior to baseline/day 1. * oral or injection of rbv within 3 months prior to baseline/day 1. * systemic use of potent immunomodulators (eg, adrenocortical hormone, thymosin alpha, etc.) for more than 2 weeks prior to baseline/day 1, or expected to be exposed to these agents during the study. * use of amiodarone within 2 months before baseline/day 1. * positive for hepatitis b surface antigen (hbsag) or anti-human immunodeficiency virus antibody (hiv ab) at screening. * evidence of decompensatory liver function, including but not limited to total serum bilirubin (tbil) above twice of the upper limit of normal (uln), serum albumin (alb) below 35 g/l or prothrombin activity (pta) below 60% confirmed on repeated testing, previous or present history of ascites, upper gastrointestinal bleeding and/or hepatic encephalopathy, or with a liver function reserve of child-pugh class b or c. * primary liver cancer confirmed or evidenced by serum alfa-fetoprotein (afp) above 100 ng/ml or liver imaging study showing suspected nodules. * liver disease of a non-hcv etiology (e.g. alcoholic liver disease, nonalcoholic steatohepatitis, drug-induced hepatitis, autoimmune hepatitis, wilson disease or hemochromatosis, etc.). * subjects has the following laboratory parameters at screening: alt or ast\>10×uln, wbc \ 1.5×uln, clcr \< 50 ml/min（calculated by the cockcroft-gault equation ）. * uncontrolled diabetes mellitus (hba1c \> 8.0% at screening). * uncontrolled hyperthyroidism or diminished. * psychiatric or neurologic disorders, including previous or family history of psychiatric disorders (especially depression, depressive state, epilepsy or hysteria). * serious cardiovascular disorders, including uncontrolled hypertension (systolic blood pressure ≥ 160 mmhg and/or diastolic blood pressure ≥100 mmhg), heart insufficiency of new york heart association class iii or above, history of myocardial infarction within 6 months before the screening, history of percutaneous transluminal coronary angioplasty within 6 months before the screening, unstable angina pectoris, or qtc interval (fridericia correction formula qtc = qt×rr\^-1/3) at or above 450 mse, second- or third-grade atrioventricular block or any other uncontrolled arrhythmias confirmed on repeated electrocardiography on screening. * serious hematologic disorders (e.g. anemia, hemophilia, etc.). * serious kidney diseases (e.g. chronic kidney disease, kidney insufficiency, etc.). * serious gastrointestinal disorders, (e.g. peptic ulcer, colitis, etc.) or post operative condition that could interfere with the absorption of the study drug. * serious respirator disorders, (e.g. active pulmonary tuberculosis, lung infection, chronic obstructive pulmonary disease, pulmonary interstitial disease, etc.). * malignancy within the 5 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc). * solid organ transplantation. * hypersensitive predisposition or a known history of serious allergy, especially to the investigational products and substances. * positive urine drug screening at screening, or clinically-relevant alcohol or drug abuse within 12 months of screening, and compliance and effectiveness evaluated by the investigator. * positive screening serum pregnancy test or baseline/day 1 serum or urine pregnancy test, and women are confirmed in pregnancy or lactation. * women of childbearing age (menopausal women aged ≤ 50 years old are also considered to have fertility), or partners who are women of childbearing age cannot comply with voluntary effective contraceptive measures during the 6 months from screening to the last dose of test drug. * use of any prohibited concomitant medications as described in protocol. * participated in clinical studies or previously participated within 3 months prior to baseline/day 1. * conditions which investigator judges that it is not suitable for enrollment.

Keywords: hepatitis c virus sh229