Case study: Astral 3
A phase 3 randomised trial of Sofosbuvir/ Velpatasvir in Genotype 3 hepatitis C
• The study ran over four months from August to December 2014
• 83 patients with HCV genotype 3 were recruited to the study by the NIHR
• The study was delivered from 10 NIHR funded sites
• Funded by Gilead Sciences Inc
• Chief Investigator: Professor Graham Foster, Professor of Hepatology at Queen Mary University of London
• The treatment of HCV genotype 3 with Sofosbuvir and Velpatasvir has been approved by NICE
It is estimated that around 214,000 individuals in the UK are chronically infected with hepatitis C, a virus most commonly transmitted through blood-to-blood contact. Without adequate treatment, hepatitis C can cause serious liver damage and potentially life-threatening complications.There are six strains of the hepatitis C virus (HCV) and genotype 3 is one of the most common types in the UK. Prior to the Astral 3 study, standard treatment for HCV genotype 3 consisted of either interferon based therapies (interferon is an injectable drug with numerous side effects, some of which may be long lasting) or a combination of sofosbuvir and ribavirin for 24 weeks.
The treatment time for this combination is lengthy and has significant side effects, such as anaemia due to ribavirin and it also has low cure rates. This is particularly evident in those who have complications of their infection including cirrhosis (liver damage). A new interferon, side-effect free and effective therapy was required to treat patients with HCV genotype 3 and the Astral 3 clinical research study addressed this.
Outcomes and findings
Patients who had previously been treated for with HCV genotype 3 and those who hadn’t, including those without evidence of liver damage, were eligible for the study. 302 patients were recruited to the study worldwide and 83 recruited to the study by the NIHR. Patients were randomised into either a 12 week course of treatment with a combination of Sofosbuvir and Velpatasvir or the combination of Sofosbuvir and Ribavirin for 24 weeks.
Astral 3 was a multi-site study which ran over four months from August until December 2014 and was sponsored by Gilead Sciences Inc. The National Institute for Health Research (NIHR) Clinical Research Network supported the setup of the study locally, funded research nurse time and recruited patients to the study. The study found that in patients taking the combination of Sofosbuvir and Velpatasvir for 12 weeks, there was a 90 per cent success rate with minimal side effects. This was a higher success rate than Sofosbuvir and Ribavirin combination. The new treatment regimen is more effective than previous therapies and allows patients with advanced disease of HCV genotype 3 to clear their virus and thereby avoid complications of infection.
“This is a groundbreaking study allowing patients who have HCV Genotype 3 and cirrhosis to achieve a 90% success rate for the first time.”
Professor Graham Foster, Professor of Hepatology at Queen Mary University of London and Astral 3 Chief Investigator
Value to the NHS
The new treatment avoids the use of injectable anti-viral interferon, significantly reduces the side effects and reduces the amount of clinical support required for patients. Since announcing the results of the study, the treatment of HCV genotype 3 with Sofosbuvir and Velpatasvir has been approved by NICE and provides a cost-effective treatment that is acceptable to patients and clinicians. Further studies funded by the NIHR funded are underway and these are looking at ways to identify and manage the small proportion of patients who do not benefit from this regimen.
• The Lancet 2011
• Study site: www.nejm.org/doi/full/10.1056/NEJMoa1512612