Ledipasvir/Sofosbuvir for Hepatitis B Virus Infection

Inclusion criteria

Participants in Groups A, C & D (Chronic HBV, low replicative state not requiring treatment):

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 or older at screening
• Diagnosed with chronic hepatitis B infection defined as one of the following:

• HBsAg or HBV DNA positivity for at least 6 months
• Medical records indicating a chronic HBV infection
• HBeAg negative at screening
• HBV DNA > lower level of quantitation (LLOQ)
• Quantitative HBsAg at least 10 IU/mL at screening
• Ability to take oral medication and be willing to adhere to the twelve week study drug regimen
• For females of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 30 days after the end of study drug administration
• For males of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 14 days after the end of study drug administration
• Ability to communicate effectively with the study investigator and key staff
• Medical management provided by a primary care provider
• Ability to store medications at a room temperature of less than 86 degrees Fahrenheit
• Not on antiviral therapy or requiring treatment for HBV during screening

Participants in Group B (Chronic HBV, virally suppressed):

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 or older at screening
• Diagnosed with chronic hepatitis B infection defined as one of the following:

• HBsAg or HBV DNA positivity for at least 6 months
• Medical records indicating a chronic HBV infection
• Receiving oral anti-HBV medications (either tenofovir alafenamide, tenofovir disoproxil fumarate, entecavir, or a combination of no more than 2 of these agents) for at least three months prior to enrollment
• HBV DNA ˂ lower level of quantitation (LLOQ) at screening and for at least three months prior
• Quantitative HBsAg at least 10 IU/mL at screening
• Ability to take oral medication and be willing to adhere to the twelve week study drug regimen
• For females of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 30 days after the end of study drug administration
• For males of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 14 days after the end of study drug administration
• Ability to communicate effectively with the study investigator and key staff
• Medical management provided by a primary care provider
• Ability to store medications at a room temperature of less than 86 degrees Fahrenheit

Exclusion criteria

• Coinfection with hepatitis C, hepatitis D or human immunodeficiency virus (HIV)
• Pregnancy or lactation
• Known allergic reactions to sofosbuvir or ledipasvir
• Treatment with another investigational drug or other intervention within three months
• Evidence of cirrhosis or hepatic decompensation such as:

• Platelets less than 100,000 /mm3
• Albumin less than 3.5 g/dL
• INR greater than 1.7 or Prothrombin time of 1.5 times the upper limit of normal (ULN)
• Total bilirubin of 1.5 times the upper limit of normal
• FibroTest (or FibroSure®) of 0.75 or greater
• Abnormal hematological and biochemical parameters at screening including:

• White blood cell count less than 2500 cells/uL
• Absolute neutrophil count (ANC) less than 1,000 cells/mm3 (less than 750 mm3 for African or African-American subjects)
• Hemoglobin less than 12 g/dL for males, less than 11 g/dL for females
• AST or ALT of two times the upper limit of normal
• Estimated GFR less than 50 mL/min
• Glycosylated hemoglobin (HbA1c) greater than 8.5%
• Current or prior history of any of the following:

• Immunodeficiency disorders or autoimmune disease (e.g. Systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel diseases, sarcoidosis, psoriasis of greater than mild severity)
• Severe pulmonary disorders, significant cardiac diseases
• Gastrointestinal disorder with post-operative condition that could interfere with the absorption of the study drugs
• Significant psychiatric illness that in the judgment of the Investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent
• Any malignancy diagnosed within 5 years (not including recent localized treatment of squamous or non-invasive basal cell skin cancer; cervical carcinoma in situ appropriately treated prior to screening)
• Solid organ transplantation
• Poor venous access
• Screening ECG with clinically significant findings
• Evidence of HCC (e.g., α fetoprotein > 50ng/mL or radiologic evidence)
• Clinically significant illicit drug or alcohol abuse within 12 months of screening. Subjects on methadone maintenance treatment or prescribed opioid may be included.
• Use of amiodarone within 90 days of enrollment; or carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifampin, rifapentine, St. John's wort, rosuvastatin, or interferon within 30 days of enrollment or expected use of these prohibited drugs during study participation. Use of or expected need of proton-pump inhibitors more than 20 mg omeprazole equivalent or H2 receptor antagonist more than 40 mg famotidine BID equivalent within 7 days of enrollment.