Ledipasvir/Sofosbuvir for Hepatitis B Virus Infection
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Virus Diseases; Herpesviridae Infections; Hepatitis
Intervention: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]; Sofosbuvir 400 MG [Sovaldi]; Ledipasvir 90 MG
Intervention description: 1 pill once daily for 12 weeks for Group A; 1 pill once daily for 12 weeks for Group C; 1 pill once daily for 12 weeks for Group D
Intervention MeSH terms: Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Open-label Study, multi-arm
Masking: None (Open Label)
Masking description: Ten potential subjects for Groups C and D will be randomized in a 1:1 fashion.
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hepatitis B; HBsAg; Ledipasvir/Sofosbuvir; Hepatitis B treatment

Summary:

      The goals of therapy against chronic hepatitis B are to decrease the morbidity and mortality
      related to chronic HBV infection. Currently available antiviral therapy can suppress viral
      replication but only a small proportion attain functional cure, which is defined as HBV
      surface antigen-to-antibody seroconversion. Hepatitis B surface antigen (HBsAg) is a marker
      of persistent hepatitis B infection.

      It has been observed that patients who had both hepatitis B and hepatitis C, and who were
      treated for their hepatitis C with 12 weeks of ledipasvir/sofosbuvir for had a decline in
      HBsAg levels. This study hypothesizes that a similar decrease would be seen in mono-infected
      hepatitis B subjects over the course of 12 weeks treatment with ledipasvir/sofosbuvir.
    

Eligibility criteria:

        INCLUSION CRITERIA

        Participants in Groups A, C & D (Chronic HBV, low replicative state not requiring
        treatment):

          1. Provision of signed and dated informed consent form

          2. Stated willingness to comply with all study procedures and availability for the
             duration of the study

          3. Male or female, aged 18 or older at screening

          4. Diagnosed with chronic hepatitis B infection defined as one of the following:

               1. HBsAg or HBV DNA positivity for at least 6 months

               2. Medical records indicating a chronic HBV infection

          5. HBeAg negative at screening

          6. HBV DNA > lower level of quantitation (LLOQ)

          7. Quantitative HBsAg at least 10 IU/mL at screening

          8. Ability to take oral medication and be willing to adhere to the twelve week study drug
             regimen

          9. 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

         10. 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

         11. Ability to communicate effectively with the study investigator and key staff

         12. Medical management provided by a primary care provider

         13. Ability to store medications at a room temperature of less than 86 degrees Fahrenheit

         14. Not on antiviral therapy or requiring treatment for HBV during screening

        Participants in Group B (Chronic HBV, virally suppressed):

          1. Provision of signed and dated informed consent form

          2. Stated willingness to comply with all study procedures and availability for the
             duration of the study

          3. Male or female, aged 18 or older at screening

          4. Diagnosed with chronic hepatitis B infection defined as one of the following:

               1. HBsAg or HBV DNA positivity for at least 6 months

               2. Medical records indicating a chronic HBV infection

          5. 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

          6. HBV DNA ˂ lower level of quantitation (LLOQ) at screening and for at least three
             months prior

          7. Quantitative HBsAg at least 10 IU/mL at screening

          8. Ability to take oral medication and be willing to adhere to the twelve week study drug
             regimen

          9. 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

         10. 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

         11. Ability to communicate effectively with the study investigator and key staff

         12. Medical management provided by a primary care provider

         13. Ability to store medications at a room temperature of less than 86 degrees Fahrenheit

        EXCLUSION CRITERIA

          1. Coinfection with hepatitis C, hepatitis D or human immunodeficiency virus (HIV)

          2. Pregnancy or lactation

          3. Known allergic reactions to sofosbuvir or ledipasvir

          4. Treatment with another investigational drug or other intervention within three months

          5. 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

          6. 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%

          7. 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

          8. Screening ECG with clinically significant findings

          9. Evidence of HCC (e.g., α fetoprotein > 50ng/mL or radiologic evidence)

         10. Clinically significant illicit drug or alcohol abuse within 12 months of screening.
             Subjects on methadone maintenance treatment or prescribed opioid may be included.

         11. 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.