DAA-based Therapy for Recently Acquired Hepatitis C II (DAA = Directly Acting Antiviral)
DAA-based Therapy for Recently Acquired Hepatitis C II (DAA = Directly Acting Antiviral)
The purpose of the study is to examine whether patients who have acute or early chronic
 hepatitis C virus (HCV) infection can be treated effectively and safely with an
 interferon-sparing regimen that combines a new direct acting antiviral drug (sofosbuvir) with
 one of the standard treatments for chronic hepatitis C (ribavirin). In particular, this study
 will investigate whether treatment of acute or early chronic HCV can be shortened. The study
 will assess efficacy by looking at the proportion of people who clear the virus (have no
 virus detectable in their blood) at the end of treatment, and 1, 3 and 6 months after
 treatment.

 The hypothesis is that short course (6 weeks) dual therapy using sofosbuvir and RBV will
 result in successful virological eradication in the majority (≥80%) of subjects treated for
 recently acquired HCV.
To evaluate the efficacy, safety and acceptability of an interferon-sparing strategy with
 sofosbuvir and ribavirin for the treatment of recently acquired HCV infection.

 An open label single arm multicentre study Treatment of participants: Sofosbuvir 400mg daily
 with weight based ribavirin (1000mg <75 kg, 1200mg >/= 75kg) Duration of treatment will be 6
 weeks for all subjects followed by 52 weeks of observational follow-up Total study duration =
 58 weeks Primary endpoint: SVR 12
Inclusion Criteria:

 -  Provision of written informed consent

 -  Male and female patients aged 18 years and above

 -  Willing to use two effective methods of contraception during the treatment period and
 24 weeks post.

 -  HBsAg negative

 -  Detectable HCV RNA at screening (>10,000 IU/ml), and in the opinion of the
 investigator is unlikely to demonstrate spontaneous viral clearance

 -  Compensated liver disease (Child-Pugh A)

 -  Negative pregnancy test at screening and 24 hours prior to first dose of study drugs

 -  Medically stable on the basis of physical examination, medical history and vital signs

 -  Adequate English to provide reliable responses to the study questionnaires

 -  Recent hepatitis C infection, as defined by: A) i) First anti-HCV Ab or HCV RNA
 positive within the previous 6 months and ii) Documented anti-HCV Ab negative within
 the 24 months prior to anti-HCV antibody positive result, OR B) i) First anti-HCV Ab
 or HCV RNA positive within the previous 6 months and ii) acute clinical hepatitis
 (jaundice or ALT> 10 X ULN) within the previous 12 months prior to first positive HCV
 antibody or HCV RNA, with no other cause of acute hepatitis identifiable

 If co-infection with HIV is documented, the subject must meet the following criteria:

 -  Antiretroviral (ARV) untreated for >8 weeks preceding screening visit with CD4 T cell
 count >500 cells/mm3 OR

 -  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.

 Exclusion Criteria:

 -  Standard exclusions to RBV therapy

 -  Pregnancy/lactation or male subjects whose female partners are pregnant

 -  Subject has a history of decompensated liver disease: history of ascites, hepatic
 encephalopathy, or bleeding oesophageal varices, and/or any of the following screening
 laboratory results: a.INR of ≥1.5; Serum albumin <3.3 g/dL; Serum total bilirubin >1.8
 times upper limit of normal, unless isolated in subjects with Gilbert's syndrome.