This is an open label phase II/III, multicenter, trial to assess the efficacy, safety, tolerance, and pharmacokinetics of sofosbuvir plus ravidasvir in HCV (+/-HIV) chronically infected adults with no or compensated cirrhosis in Thailand and Malaysia
Brief Summary: The study will assess the efficacy and safety of SOF-RDV across all genotypes, among non-cirrhotic and cirrhotic with CTP class A, interferon/ribavirin naïve or experienced, HCV mono-infected and HCV/HIV co-infected subjects.
It will also study the pharmacokinetics of RDV and, in HCV/HIV co-infected subjects, possible drug-drug interactions with antiretrovirals.
The treatment duration will be 12 weeks for subjects with no cirrhosis (Metavir F0 to F3) and 24 weeks for subjects with compensated cirrhosis (Metavir F4, CTP class A). After enrollment of the first 300 evaluable patients is complete, enrollment will pause while data is being accumulated and analyzed.
After review of interim results by the independent Data and Safety Monitoring Board (DSMB), and by the study Steering Committee, enrollment will resume.
Should modification of the study design be required upon interim analysis, decision will be taken by the study steering committee and the amended protocol or expanded protocol will be submitted to the Ethics Committee for approval.
Results: Of the 25 subjects with intensive PK data: 21 were male (84%) and 21 non-cirrhotic (4 cirrhotic). Median age (range) was 49.2 (21.2-64.0) years, weight was 65.5 (46.2-88.3) kg and body mass index 23.3 (18.3-30.9) kg/ m2. Median RDV AUC0-24h, Cmax and C24 were 17.3 (3.2-69.9) μg.hr/mL, 2.3 (0.4-6.4) μg/mL and 0.11 (0.03-1.63) μg/mL, respectively. Sixty-five HIV/HCV co-infected subjects were included: median age (range) was 42.9 (23.4-61.5) years and weight 62.0 (45.0-100) kg. Tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), efavirenz (EFV) and nevirapine (NVP) were the most commonly prescribed ARVs in HIV/HCV co-infected patients. A total of 47 subjects had tenofovir (TFV) ARVs concentrations before and after SOF/RDV treatment, 34 had FTC, 51 had EFV and 7 had NVP. Mid-dose tenofovir (TFV) concentrations were significantly higher with concomitant SOF/RDV treatment, while mid-dose FTC, EFV and trough NVP concentrations were not significantly different.
(Source: Cressey TR, et al. Ravidasvir pharmacokinetics and ARV drugs interactions in HCV+/-HIV infected adults. Abstract #471. Presented at CROI 2018)
