Randomised Study of Interferon-free Treatment for Recently Acquired Hepatitis C in PWID and People With HIV Coinfection.
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Coinfection; HIV Infections; Hepatitis
Intervention: SOF/VEL for 6 weeks; SOF/VEL for 12 weeks
Intervention description: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm A (6 weeks short treatment duration).; Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm B (12 weeks standard treatment duration).
Intervention MeSH terms: Sofosbuvir; Velpatasvir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 222.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The aim of the study is to determine if treatment for recently acquired hepatitis C infection
      (with or without HIV coinfection) can be shortened when treating with the interferon-free
      therapy sofosbuvir/velpatasvir (SOF/VEL).

      SOF/VEL is a new treatment for hepatitis C called direct acting antiviral which targets the
      hepatitis C virus replication cycle and has been shown in phase II studies in chronic HCV to
      be highly effective (SVR12 >95%) when given for 12 weeks.

      Data has shown that treatment can be shortened when treating recently acquired HCV with
      interferon containing treatments. It is not known whether treatment with SOF/VEL can be
      shortened.

      This study aims to find out if treatment for 6 weeks with open-label SOF/VEL is equivalent to
      treatment for 12 weeks with SOF/VEL in participants with recently acquired hepatitis C
      infection. The project is a randomised study where both participants and investigators would
      not find out the treatment duration of the participants until week 6 of treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must meet all of the following inclusion criteria to be eligible to
             participate in this study:

               1. Participants have voluntarily signed the informed consent form.

               2. 18 years of age or older.

               3. Detectable HCV RNA at screening (>10,000 IU/ml), and in the opinion of the
                  investigator is unlikely to demonstrate spontaneous viral clearance

               4. HCV genotypes 1-6.

               5. HBsAg negative

               6. Compensated liver disease (Child-Pugh A)

               7. Negative pregnancy test at baseline (females of childbearing potential only).

               8. Medically stable on the basis of physical examination, medical history and vital
                  signs

               9. Adequate English to provide reliable responses to the study questionnaires

              10. All fertile males and females must be using effective contraception during
                  treatment and during the 30 days after treatment end.

              11. Recently acquired HCV infection (estimated duration of infection ≤12 months)*

        Recently acquired HCV infection as defined by:

        A) i) First anti-HCV Ab or HCV RNA positive within the previous 3 months and ii) Documented
        anti-HCV Ab negative within the 12 months prior to anti-HCV antibody positive result

        OR

        B) i) First anti-HCV Ab or HCV RNA positive within the previous 3 months and ii) Acute
        clinical hepatitis [jaundice or alanine aminotransferase (ALT)] > 10 X ULN) within the
        previous 6 months prior to first positive HCV antibody or HCV RNA, with no other cause of
        acute hepatitis identifiable

        OR

        C) For cases of recent HCV reinfection the following criteria are required:

        Documented prior HCV antibody positive with HCV RNA negative on at least 2 occasions 6
        months apart AND new HCV RNA positive within the previous 6 months

        *Estimated duration of infection based on midpoint between last antibody negative or HCV
        RNA and first antibody positive or HCV RNA in the case of seroconversion and 6 weeks prior
        to date of maximum ALT in the case of acute hepatitis.

        If co-infection with HIV is documented, the subject must meet the following criteria:

          1. Antiretroviral (ARV) untreated for >8 weeks preceding screening visit with cluster of
             differentiation 4 (CD4) T cell count >500 cells/mm3 OR

          2. On a stable ARV regimen for >8 weeks prior to screening visit, with CD4 T cell count
             >200 cells/mm3 and an undetectable plasma HIV RNA level.

               -  Suitable ARV include:

                    -  Tenofovir (TDF) and tenofovir alafenamide (TAF)

                    -  Emtricitabine (FTC)

                    -  Rilpivirine

                    -  Dolutegravir

                    -  Elvitegravir/cobicistat

               -  Contraindicated ARV include:

                    -  Efavirenz 50% reduction in velpatasvir (GS-5816) exposure

                    -  Didanosine

                    -  Zidovudine

                    -  Tipranavir Other ARV agents may be permissible at the time of study
                       commencement pending further drug-drug interaction studies; please discuss
                       with Study Principal Investigator.

        Exclusion criteria:

        Subjects who meet any of the exclusion criteria are not to be enrolled in this study.

          1. History of any of the following:

               1. Clinically significant illness (other than HCV) or any other major medical
                  disorder that may interfere with the participant treatment, assessment or
                  compliance with the protocol; participants currently under evaluation for a
                  potentially clinically significant illness (other than HCV) are also excluded.

               2. History of chronic pulmonary disease associated with functional limitation,
                  severe cardiac disease, major organ transplantation or other evidence of severe
                  illness, malignancy, or any other conditions which would make the patient, in the
                  opinion of the investigator, unsuitable for the study

               3. Solid organ transplant

               4. Malignancy within 5 years prior to screening, with exception of specific cancers
                  that may have been cured by surgical resection (basal cell skin cancer, etc.).
                  Subjects under evaluation for possible malignancy are also excluded.

               5. Significant drug allergy (such as anaphylaxis or hepatotoxicity).

          2. Subject shows evidence of significant liver disease in addition to hepatitis C, which
             may include but is not limited to drug- or alcohol-related cirrhosis, autoimmune
             hepatitis, hemochromatosis, Wilson's disease, non-alcoholic steatohepatitis (NASH), or
             primary biliary cirrhosis

          3. Subject has known cirrhosis

          4. Any of the following lab parameters at screening:

               1. Direct bilirubin > 1.5 x ULN

               2. Platelets < 50,000/μL

               3. Creatinine clearance (CLcr) < 60 mL/min

               4. Haemoglobin < 11 g/dL for females ; < 12 g/dL for males

               5. Albumin < 30g/L

          5. Pregnant or nursing female.

          6. Use of prohibited concomitant medications as described in section 5.2 in the protocol

          7. Chronic use of systemically administered immunosuppressive agents (e.g. prednisone
             equivalent > 10 mg/day)

          8. Known hypersensitivity to velpatasvir, sofosbuvir or formulation excipients.

          9. Therapy with any anti-neoplastic or immunomodulatory treatment (including
             supraphysiologic doses of steroids and radiation) ≤6 months prior to the first dose of
             study drug.

         10. Any investigational drug ≤6 weeks prior to the first dose of study drug.

         11. Previous failure of therapy with sofosbuvir or an non-structural protein 5A (NS5A)
             inhibitor prior to the first dose of study drug.

         12. Ongoing severe psychiatric disease as judged by the treating physician.

         13. Frequent injecting drug use that is judged by the treating physician to compromise
             treatment safety.

         14. Inability or unwillingness to provide informed consent or abide by the requirements of
             the study.