Intervention: Ledipasvir and sofosbuvir
Trial phase: Phase 2
ATC code: J05AP51
SMILES: CC(C)OC(=O)C(C)NP(=O)(OCC1OC(n2ccc(=O)[nH]c2=O)C(C)(F)C1O)Oc1ccccc1.COC(=O)NC(C(=O)N1CC2(CC2)CC1c1ncc(-c2ccc3c(c2)C(F)(F)c2cc(-c4ccc5nc(C6C7CCC(C7)N6C(=O)C(NC(=O)OC)C(C)C)[nH]c5c4)ccc2-3)[nH]1)C(C)C
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 8
Group description: 12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B in low replicative state.

Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]: 1 pill once daily for 12 weeks for Group A
Eligibility criteria:
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.