DAA-based Therapy for Recently Acquired Hepatitis C II (DAA = Directly Acting Antiviral) (DARE-C II)

An Interferon Sparing Strategy of Sofosbuvir Plus Ribavirin for the Treatment of Recently Acquired Hepatitis C Infection

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Sofosbuvir and ribavirin

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • St Vincent's Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3050
      • Royal Melbourne Hospital
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
• New Zealand
  • Grafton
    • Auckland, Grafton, New Zealand, 1023
      • Auckland City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sofosbuvir and ribavirin; Sofosbuvir tablet 400 mg daily Ribavirin tablet weight based dosing (1000mg <75 kg, 1200mg >/= 75kg) daily Treatment will be for 6 weeks in all participants.	Drug: Sofosbuvir and ribavirin; Sofosbuvir 400mg daily plus weight-based dosing ribavirin (1000mg <75kg, 1200mg >/= 75 kg) Treatment will be for 6 weeks in all participants.; Other Names: Copegus; Sovaldi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SVR 12	Proportion of patients with undetectable HCV RNA by TaqMan 12 weeks after therapy completion (SVR 12 - Week 18)	12 weeks post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SVR 24	Proportion of patients with undetectable HCV RNA by TaqMan 24 weeks after therapy completion (SVR 24 - Week 30)	24 weeks post treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
End of treatment response	Proportion of patients with undetectable HCV RNA at end of therapy (ETR - week 6)	End of treatment week 6
SVR 4	Proportion of patients with undetectable HCV RNA by TaqMan 4 weeks after therapy completion (SVR 4 - Week 10)	4 weeks post treatment
Follow up 1 year	Proportion of patients with undetectable HCV RNA at end of study follow-up (FU1 - Week 58)	1 year post treatment
Undetectable HCV RNA	Proportion of patients with undetectable HCV RNA at weeks 1, 2, 3 and 4	Week 1, 2, 3 and 4 of treatment
Indicators of toxicity (ALT, HB, Neutrophils, Platelets)	To evaluate indicators of toxicity (ALT, HB, Neutrophils, Platelets) during therapy	Baseline until week 4 of treatment
Plasma ribavirin levels and haemoglobin	To correlate plasma ribavirin levels with treatment outcome and changes in haemoglobin during therapy	Baseline to week 4 of treatment
Incidence of reinfection	Incidence of reinfection after documented SVR	End of treatment until follow up 1 year

Collaborators and Investigators

• Sponsor: Kirby Institute
• Investigators: Principal Investigator: Gail Matthews, MbChB FRACP, Kirby Institute

Publications and helpful links

Helpful Links

• UNSW Kirby Institute for infection and immunity in society Homepage

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: June 3, 2014
• First Submitted That Met QC Criteria: June 3, 2014
• First Posted (Estimate): June 5, 2014

Study Record Updates

• Last Update Posted (Actual): September 21, 2018
• Last Update Submitted That Met QC Criteria: September 19, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Hepatitis C; Sofosbuvir; Ribavirin; Acute/early chronic; Recently acquired; Directly acting antiviral therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Sofosbuvir; Ribavirin
• Other Study ID Numbers: VHCRP1206