Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Signed Written Informed Consent
Males or females 18-55 years of age
HBsAg> 1000 IU / ml at screening
HBV DNA > 10000 copies / ml at screening
Seronegative for HIV, HCV, CMV (IgM) and HDV (anti-HDAg) as determined at screening visit
HBeAg negative, anti-HBe positive
Evidence of liver fibrosis at screening
Non cirrhotic: absence of advanced cirrhosis based on fibroscan evaluation at screening.

Willingness to utilize adequate contraception while being treated with REP 2139-Mg or REP 2165-Mg and for 6 months following the end of the treatment in the study

Any woman of childbearing potential (WOCBP) who agrees to use an effective methods of birth control for the entire duration of the study.
Sexually active men who agree to use an effective method of birth control if their partners are WOCBP for the entire duration of the study for 6 months following the end of treatment.
Body Mass Index (BMI) ≥ 18 kg/m2 and ≤ 30kg/m2 at screening (http://www.nhlbisupport.com/bmi/bmicalc.htm)
Adequate venous access allowing weekly intravenous therapies and blood tests

Exclusion Criteria:

Women with positive serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG).
Breast-feeding women.
HBeAg positive as determined at screening visit
Positive HCV antibody, or HIV-1/HIV-2 or CMV antibody (IgM) or anti-HDV antibody test at screening
Evidence of chronic liver disease caused by diseases other than chronic HBV infection (such as but not limited to: severe NAFLD, Wilson's disease, hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, significant biliary disease, nonalcoholic hepatic steatosis and toxin exposure).

Medical History and Concurrent Diseases

Current evidence of or history of variceal hemorrhage, hepatic encephalopathy, or ascites requiring diuretics or paracentesis or evidence of any of these findings on physical examination performed at screening
Documented or suspected HCC as evidenced by previously obtained imaging studies or liver biopsy.
Current evidence of or history of pancreatitis
Current evidence of or history of renal dialysis, including hemodialysis or peritoneal dialysis
History of bone marrow or organ transplant (other than cornea or hair), including liver transplant, or therapy with an immunomodulatory agent, cytotoxic agent, or systemic corticosteroids within 2 months of screening
Current or known history of cancer (except adequately treated in situ carcinoma of the cervix, or basal or squamous cell carcinoma of the skin) within 5 years prior to screening
Subjects with clinically significant ECG abnormalities (indicative of arrhythmia, myocardial ischemia or other serious cardiovascular disorder) at the time of screening in the opinion of the investigator
Active substance abuse, such as alcohol, or inhaled or injected drugs, as defined by Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), Diagnostic Criteria for Drug and Alcohol Abuse (see Appendix 1) within 12 months prior to screening.
The use of illicit drugs within the past two years prior to screening.
Prior or current history of cardiomyopathy or significant ischemic cardiac or cerebrovascular disease, including history of angina, myocardial infarction, or interventional procedure for coronary artery disease (including angioplasty, stent procedure, or cardiac bypass surgery)
Confirmed uncontrolled hypertension (patients with screening systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg should be excluded unless discussed with Replicor Inc.)
Presence of diabetes (controlled or uncontrolled).
Prior or current history of clinically significant hemoglobinopathy or hemolytic anemia
History of or evidence of hyperthyroidism at screening.
Subjects with pre-existing ophthalmologic disorders considered clinically significant on eye exam during physical examination.
Prior or current history of severe chronic obstructive pulmonary disease, interstitial lung disease or sarcoidosis
History of immunologically mediated disease (including but not limited to, rheumatoid arthritis, inflammatory bowel disease, moderate to severe psoriasis [mild psoriasis is allowed], and systemic lupus erythematosus)
History of or current severe psychiatric disease, especially untreated or unstable depression, psychotic disorder such as bipolar disease and history of hospitalization for suicidal ideation/attempt
Active seizure disorder as defined by either untreated seizure disorder or continued seizure activity within the past year prior to screening despite treatment with anti-seizure medication
Has, in the opinion of the investigator, any physical exam findings, laboratory abnormalities, or other medical, social, or psychosocial factors that may negatively impact compliance or subject's safety by participation in this study; this should include conditions which may affect hematologic parameters such as prior or current history of porphyria cutanea tarda and/or hemophilia
Fibroscan and Fibromax showing current evidence advanced cirrhosis at screening or known history of decompensated cirrhosis based on radiologic criteria or biopsy results and clinical criteria
Poor venous access making IV infusion too difficult
Inability to provide informed consent
Inability or unwillingness to provide weekly blood samples.
Patients not willing to come every week to receive therapy or to give blood.

Physical and Laboratory Test Findings

Evidence of significant heavy metal load in whole blood as determined at pre-screening visit.
Antinuclear antibody (ANA) titer ≥ 1:640, AMA or LKM-1antibody positive as determined at pre-screening visit
Hemoglobin < 12.0 g/dL (males), < 10.0 g/dL (female) at screening
Platelet count < 90,000/mm3as determined at screening visit
Creatinine clearance (CrCl) (as estimated by Cockcroft and Gault) ≤50 mL/min or confirmed creatinine persistently>1.5 mg/dl as determined at screening visit
Total serum bilirubin>25umol/L as determined at screening visit.
INR ≥ 2.0 as determined at screening visit
PTT ≥ 2.0 x ULN as determined at screening visit
Serum albumin ≤ 3.5 g/dL (35 g/L) as determined at screening visit
ALT >10x ULN as determined at screening visit
ANC ≤ 1,500 cells/mm3 as determined at screening visit
Diagnosed or suspected hepatocellular carcinoma as evidenced by screening alpha-fetoprotein (AFP) of ≥ 100 ng/mL. If AFP is ≥ 50 ng/mL and < 100 ng/mL, absence of mass/findings suspicious for HCC must be demonstrated by ultrasound/CT/MRI within the screening period.
Diabetes mellitus as evidenced by HbA1C ≥ 8.5% at screening
QTc interval > 500 msec.
Known hypersensitivity to drugs with a similar biochemical structure to REP 2139-Mg or REP 2165-Mg (e.g. other phosphorothioate oligonucleotides) or Pegasys® (e.g. other interferons), Zadaxin® or Viread® (e.g. other nucleoside analog polymerase inhibitors such as entecavir).
Any other criteria or known contraindication that would exclude the subject from receiving REP 2139-Mg, REP 2165-Mg, Pegasys® or Viread®.
Prisoners or subjects who are involuntarily incarcerated.
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
Employees, family members, or students of the investigator or clinical site
Individuals who participated in another clinical study of a medicinal product or medical device within 90 days of signing Informed Consent Form

Concomitant Treatments with any of the following medications:

Heparin
Coumadin
Blood products within 30 days prior to study enrollment
Hematologic growth factors within 90 days prior to study enrollment
Use of any investigational product within 1 year prior to study enrollment
Systemic antibiotics, antifungals, or antivirals for treatment of active infection within 14 days of enrollment.
Previous exposure to immunotherapy with 6 months prior to enrollment.