About the Project
A phase IV, open-label, multicentre, international trial of response guided treatment with directly observed pegylated interferon alfa 2b and self-administered ribavirin for patients with chronic HCV genotype 2 or 3 infection and injection drug use.
Current standard hepatitis C genotype 2 or 3 treatment is given over 24 weeks as weekly subcutaneous injections of PEGIFN alfa (at a dose of 1.5 μg per kilogram of body weight) in combination with twice daily oral doses of RBV (at 8001400mg/day depending on weight).
Sustained virological response to treatment in participants with genotype 2 or 3 is achieved in 76% of patients.
Side effects are common with hepatitis C treatment and treatment is expensive, as average treatment cost per patient is estimated to be around $20,000 USD. Efforts have therefore been made to identify patients who may respond to shorter treatment than what current guidelines propose.
Viral load measurement (a measure of the amount of hepatitis C virus RNA in the blood) is performed at baseline and at weeks 4 and 12 in order to better understand the response to therapy. Individuals with undetectable HCV RNA at week 4 and 12 are said to have rapid virological response (RVR) and early virological response (EVR), respectively. A rapid virologic response after 4 weeks of therapy is predictive of SVR. Among patients with genotype 2 or 3 and an RVR at week 4, SVR may be achieved in 8095% as compared to 50% of those with no RVR.
Some research into shortened treatment in patients with a RVR has been conducted. A posthoc analysis of one trial demonstrated similar responses in patients with RVR who received 24 or 48 weeks of treatment with PEGIFN alfa/RBV, respectively. Data from a pilot trial and two randomized controlled trials have shown comparable SVR rates in patients with genotype 2 or 3 infection and RVR, treated for 1214 weeks compared to 24 weeks of therapy. Further, in a recent pooled analysis of two Scandinavian treatment trials in patients with RVR and genotype 2 or 3, SVR was obtained in 91% and 95% after 14 or 24 weeks treatment with PEGIFN alfa2b/RBV.
These results are in contrast to other studies such as the ACCELARATE trial and the Nordynamic trial which both concluded after posthoc analyses of those with RVR, that 12 and 16 weeks, respectively, was inferior to 24 weeks treatment. However, both the ACCELARATE trial and the Nordynamic trial used a fixed 800 mg dose of RBV, while the Mangia and Dalgard studies used higher weight based dosing (8001400mg). This may explain the different findings and the different conclusions.
The primary objective is to evaluate the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following directly observed PEG-IFN alfa-2b (1.5 μg/kg weekly, to a maximum of 150 μg/week) in combination with self-administered ribavirin (800-1400 milligrams daily) for 12 weeks in participants with non-quantifiable (i.e. <15 IU/ml detected and <15 IU/ml undetected) HCV RNA or undetectable HCV RNA on qualitative assay at week 4 of therapy and for 24 weeks in participants with quantifiable HCV RNA (i.e. ≥15 IU/ml) or detectable HCV RNA on qualitative assay at week 4 of therapy. In this feasibility study, the primary endpoint measurement of efficacy of treatment will be SVR12.
The secondary objectives are:
to evaluate the percentage adherent to therapy (>80% of PEG-IFN, >80% of RBV, >80% of time)
to evaluate safety and tolerability
to evaluate the rate of recruitment
to compare the percentage of patients with ETR and SVR24 among those who receive HCV therapy for 12 weeks (non-quantifiable HCV RNA [i.e. <15 IU/ml detected and <15 IU/ml undetected] or undetectable HCV RNA on qualitative assay at week 4) and 24 weeks (quantifiable HCV RNA [i.e. >15 IU/ml] or detectable HCV RNA on qualitative assay HCV RNA at week 4)
to evaluate the change in illicit drug use during treatment
to evaluate the change in opiate substitution therapy during treatment
to evaluate the change in depression and suicidal ideations during treatment
to evaluate the change in health related quality of life during treatment
to evaluate the percentage of enrolled patients with a satisfactory completed CRF
to allow the collection and storage of DNA and plasma samples with the aim of establishing a specimen bank for future immunovirological studies of HCV
to study host genetic factors associated with HCV outcomes
Design & Method
This study will be conducted as a phase IV, international, multi-centre trial using an open-label design. Eligible subjects (active injection drug users or recipients of opiate substitution therapy with HCV genotype 2 or 3) will be treated with either 12 weeks or 24 weeks of PEG-IFN and RBV based on week 4 (RVR) virological response. All participants will be followed up for 24 weeks following their final dose of study medication. Participants will be considered active injection drug users if they have used injection drugs in the 24 weeks prior to consent. Patients with frequent drug use that is judged by the treating physician to compromise treatment safety will be excluded.
The study has completed recruitment on 31st of July 2014. 93 participants have been enrolled.
Treatment of Hepatitis C genotype 2 or 3 is expensive and is associated with multiple and often severe adverse drug reactions. If this research finds that treatment for 12 rather than 24 weeks is as effective in patients who have an early response to treatment, it may allow a reduction in cost and a reduced duration of adverse events suffered during treatment.
Multiple and often severe adverse drug reactions are associated with the treatment of hepatitis C. If this study finds that a reduced treatment duration is effective, it may reduce the duration of adverse events suffered by participants.
Professor and Program Head
Ph 02 9385 0900
Senior Research Fellow (UNSW)
Ph +61 (2) 9385 0957
Clinical Trials Manager
Ph +61 (0)2 9385 0886
Clinical Project Coordinator
Ph +61 2 9385 9970
Adrian Dunlop (Newcastle), Martin Weltman (Nepean), David Shaw (Adelaide), Margaret Hellard (Melbourne), Belgium, Brian Conway (Vancouver), Jeff Powis (Toronto), Julie Bruneau (Montreal), Graham Foster (London), Stephen Ryder (Nottingham), Markus Backmund (Munich), Philip Bruggmann (Zurich), Cornelia Staehelin (Bern), Claude Scheidegger (Basel), Olav Dalgard (Oslo), Catharina Mathei and Stefan Bourgeois (Antwerp),Geert Robaeys(Genk)
Project Collaborators: External
St Vincent’s Hospital, NSW, Australia
Burnet Institute, Alfred Hospital, VIC, Australia
Royal Adelaide Hospital, SA, Australia
Hunter Pharmacotherapy, John Hunter Hospital, NSW, Australia
Nepean Hospital, NSW, Australia
Vancouver ID Research and Care Centre Society (VIDC),Canada
Centre Hospitalier de l'Universite de Montreal, Canada
East Toronto Hepatitis C Partnership, South Riverdale Community Health Centre, Canada
ARUD, Poliklinik Zokl 1, Zurich, Switzerland
Zentrum fur Suchtmedizin, Basel, Switzerland
Koda Bern/Poliklinik fur Infektiologe, Switzerland
ZNA Stuivenberg and Free Clinic Antwerp, Belgium
Ziekenhuis Oost Limburg Genk, Belgium
Praxiszentrum Im Tal (PIT); Ludwig-Maximilians-Universitat Munich, Germany
Oslo University Hospital, Norway
Barts and the London Queen Mary’s School of Medicine and Dentistry, United Kingdom
Nottingham University Hospital, United Kingdom