Directly Observed Therapy for HCV in Chennai, India
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis C; Hepatitis C, Chronic
Intervention: Sofosbuvir; Pegylated Interferon alfa-2a; Ribavirin
Intervention description: Direct acting antiviral agent used for the treatment of hepatitis C; Antiviral agent used for the treatment of hepatitis C; Antiviral agent (guanosine analogue) used for the treatment of hepatitis C
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a; Sofosbuvir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: directly observed therapy; sofosbuvir; ribavirin; pegylated interferon; resource-limited setting

Summary:

      The primary objective of this pilot trial is to evaluate the feasibility of 12 weeks vs. 24
      weeks of field-based directly observed therapy (DOT) for HCV therapy in a resource-limited
      setting. The investigators will compare treatment completion rates among 50 persons
      chronically infected with HCV who will be randomized to receive either 1) 12 weeks of
      sofosbuvir (SOF) + ribavirin (RBV) + pegylated interferon alfa-2a (PEG); or 2) 24 weeks of
      SOF + RBV. Treatment will be delivered daily by field workers at a location of a participants
      choosing. Secondary objectives are 1) To compare the efficacy of SOF+RBV with or without PEG
      as measured by the proportion of subjects with sustained viral response at 12 weeks after
      discontinuation of therapy (SVR12); 2) To evaluate the safety and tolerability of SOF+RBV
      with or without PEG; 3) To assess the impact of SVR12 on insulin resistance.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Willing/able to provide consent

          2. Age ≥ 18

          3. Chronic HCV (HCV RNA positive)

          4. Resident of Chennai and can provide locator information

          5. If co-infected with HIV, must have CD4 (Cluster of Differentation 4) > 350 cells/mm3
             and either: 1) ART naïve or 2) if on ART be on a tenofovir-containing regimen. If a
             participant's CD4 drops below 350 cells/μl (threshold for treatment in India), will
             have to initiate a tenofovir-containing regimen (current standard of care).

          6. Participants must have the following at screening:

               1. Alanine Aminotransferase (ALT) ≤ 10 x the upper limit of normal (ULN)

               2. Aspartate Aminotransferase (AST) ≤ 10 x ULN

               3. Hemoglobin ≥ 12 g/dl for males and 11 g/dl for females

               4. International normalized ratio (INR) ≤ 1.5 x ULN unless subject has known
                  hemophilia or is stable on an anticoagulant regimen affecting INR

               5. Albumin ≥ 3 g/dl

               6. Direct bilirubin ≤ 1.5 x ULN

               7. Creatinine clearance ≥ 60 ml/min (Cockgroft-Gault Equation)

               8. Alpha fetoprotein < 50 ng/ml

               9. Absolute neutrophil count (ANC) ≥ 1,500/μL

              10. Platelets ≥ 90,000/μL

              11. Thyroid stimulating hormone (TSH) ≤ ULN

          7. A female subject is eligible if it is confirmed that she is:

               1. Not pregnant or nursing

               2. Of non-childbearing potential (i.e., women who have had hysterectomy, have both
                  ovaries removed or medically documented ovarian failure, or are postmenopausal
                  women > 50 years of age with cessation (for ≥12 months) of previously occurring
                  menses

               3. Of childbearing potential and negative urine pregnancy test prior to
                  randomization and agree to one of the following from 3 weeks prior to
                  Baseline/Day 1 until 6 months after the last dose of RBV.

                    -  Complete abstinence from intercourse.

             Or

             • Consistent use of approved methods of birth control in addition to a male partner
             who correctly uses a condom from 3 weeks prior to Baseline/Day 1 until 6 months after
             the last dose of RBV.

          8. Male participants must agree to consistently and correctly use a condom. If their
             female partner is of childbearing potential, their partner must agree to use one of
             the study approved non-hormonal methods of birth control or a hormone-containing
             contraceptive, from the date of screening until 7 months after their last dose of RBV

          9. Male participants must agree to refrain from sperm donation for at least 7 months
             after the last dose of RBV.

         10. Of generally good health as determined by the investigator.

         11. Able to comply with the dosing instructions for study drug administration and willing
             to complete the study schedule of assessments.

        Exclusion Criteria:

          1. Pregnant/nursing female or male with pregnant/nursing female partner.

          2. Current or prior history of clinical hepatic decompensation (e.g., ascites,
             encephalopathy or variceal hemorrhage, MELD<12)

          3. Prior hepatitis C treatment

          4. Infection with hepatitis B virus

          5. Chronic use of systematically administered immunosuppressive agents (e.g., prednisone
             equivalent >10 mg/day)

          6. Use of any prohibited concomitant medications within 28 days of the Baseline/Day 1
             visit.

          7. Contraindications to RBV therapy or PEG/RBV

          8. Known hypersensitivity to RBV or PEG, the metabolites or formulation excipients

          9. Additional exclusion criteria related to Aim 1 regimen

               1. Pre-existing significant psychiatric condition(s) including severe depression,
                  severe bipolar disorder and schizophrenia. Other psychiatric disorders are
                  permitted if the condition is well controlled with a stable treatment regimen for
                  ≥ 1 year from screening.

               2. Presence of autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid
                  arthritis, sarcoidosis).

               3. History of clinical significant retinal disease.