A phase II, open-label, multicentre, international trial of sofosbuvir and GS-5816 for people with chronic hepatitis C virus infection and recent injection drug use

Date Commenced:
Planned for March 2015
Project Status
Ongoing
Expected Date of Completion:
To be confirmed.
Project Supporters

Gilead Sciences Inc

Currently recruiting
No
Simplify logo

About the Project

SIMPLIFY is a phase II open label single arm multicentre international study exploring the safety, efficacy and feasibility of sofosbuvir and GS-5816 therapy for 12 weeks for patients with chronic HCV infection and recent injection drug use.

Rationale

The natural history of HCV with an increase in liver cirrhosis after 15-20 years and an ageing cohort of people who inject drugs (PWID) means that a large burden of advanced liver disease is anticipated in the next decade. Further, HCV transmission continues to occur among PWID. Targeted treatment to those potentially at higher risk of transmission could potentially be used to inform strategies for the implementation of public health and treatment-as-prevention interventions at a population level.

 

Despite revised guidelines, few PWID have received HCV treatment.Enhanced HCV assessment and treatment in PWID will be required to reduce future HCV-related morbidity and mortality.

Treatment of chronic HCV with pegylated interferon-alfa (PEG-IFN)/ribavirin is safe and effective among those with a history of injecting drug use (IDU) and among active PWID, with 54-56% attaining a sustained virological response (SVR). However, the majority of studies in this area have been limited by small sample sizes and retrospective study designs.

ACTIVATE is an international network of 17 sites across seven countries with experience in the treatment of HCV infection among PWID. The ACTIVATE study is 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 recent injection drug use or receiving OST. However, therapy with PEG-IFN and ribavirin is associated with considerable side-effects, complicating therapy among PWID.

The Gilead Sciences IFN-free dual DAA regimen of sofosbuvir 400 mg once-daily (SOF, nucleotide polymerase inhibitor) and GS-5816 100 mg once-daily (NS5A inhibitor) has demonstrated high efficacy (95-96% SVR12) with a treatment duration of 12 weeks in treatment-naïve patients with HCV genotypes 1-6 and is currently in phase III evaluation as a 12 week regimen. The availability of a simplified IFN-free DAA-based once-daily regimen of sofosbuvir/GS-5816 should considerably enhance the capacity to scale-up HCV treatment among PWID.

Aims

The purpose of the study is to evaluate the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following sofosbuvir/GS-5816 therapy for 12 weeks in people with chronic HCV infection and recent injection drug use.

The secondary objectives are:

  • To evaluate the proportion adherent to therapy (both on-treatment adherence and treatment discontinuation)
  • To evaluate the association between adherence and response to treatment;
  • To evaluate factors associated with on-treatment adherence and treatment discontinuation;
  • To evaluate the proportion of participants with undetectable HCV RNA at the end of treatment (ETR);
  •  To evaluate safety and tolerability;
  • To evaluate the change in illicit drug use during treatment;
  •  To evaluate the change in OST during treatment (dose and any discontinuation);
  •  To evaluate the change in mental health during treatment;
  • To evaluate the change in health-related quality of life during treatment;
  •  To evaluate the rate of HCV reinfection during and up to two years following treatment.
Design & Method

SIMPLIFY is a phase II open label multicentre international study. A total of 100 people with recent injection drug use, all HCV genotypes, will be enrolled and treated for 12 weeks with sofosbuvir/GS5816 (400 mg/100mg daily) in an oral once-daily fixed dose combination, followed by 96 weeks of observational follow-up.

Progress/Update

Site feasibility ongoing.

Benefits

Enhanced HCV assessment and treatment in PWID will be required to reduce future HCV-related morbidity and mortality. Currently, few PWID have received HCV treatment with pegylated interferon-alfa (PEG-IFN)/ribavirin which are associated with considerable side-effects, complicating therapy among this population. The availability of a simplified IFN-free DAA-based once-daily regimen of sofosbuvir/GS-5816 should considerably enhance the capacity to scale-up HCV treatment among PWID.

Output

Nil to date

Project Members
image - Dore
Professor and Program Head
Ph 02 9385 0900
image - Jason Grebely Replace
Senior Research Fellow (UNSW)
Ph +61 (2) 9385 0957
image - Pip Marks
Clinical Trials Manager
Ph +61 (0)2 9385 0886
image - Sophie Quiene
Clinical Project Coordinator
Ph +61 2 9385 9970
image - Danica Martinez2
Laboratory Coordinator
Ph +612 9385 0203
image - 1338425133 Janaki Amin.jpg
Associate Professor Janaki Amin
Associate Professor and Postgraduate Coordinator
image - Sharmila Siriragavan
Data Manager
Ph +61 (02) 9385 0983

Project Contacts

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