SAN FRANCISCO, CA—Results from AGATE II, the first Phase 3 trial to evaluate ombitasvir/paritaprevir/ritonavir with ribavirin for patients with chronic hepatitis C virus (HCV) genotype 4 (GT4) infection in Egypt, found the regimen to be “generally well tolerated,” according to a presentation at The Liver Meeting® 2015.

Patients in the open-label trial were both with and without compensated cirrhosis.

“Chronic hepatitis C virus infection is the main cause of liver cirrhosis and liver cancer in Egypt and one of the five leading causes of death,” noted Gamal E. Esmat, MD, of Cairo University in Cairo, Egypt. In fact, Egypt has one of the world’s highest prevalences of HCV infection. Approximately 10% to 14% of the population is infected, more than 90% with genotype 4.

Previously, the Phase 2b PEARL-I study found the direct acting antiviral agents (DAA) ombitasvir, a NS5A inhibitor, and paritaprevir, a NS3/4A protease inhibitor, co-dosed with ritonavir with or without ribavirin, to be safe and effective in 135 patients with HCV GT4 infection without cirrhosis. Sustained virologic response at 12 weeks (SVR12) was 100% in patients who were treatment-naïve as well as in those who had received prior interferon and ribavirin.

In the ongoing open-label AGATE II study, 160 patients were enrolled across 5 sites. Those without cirrhosis received co-formulated ombitasvir 25mg, paritaprevir 150mg, and ritonavir 100mg once daily with weight-based ribavirin for 12 weeks (Arm A, n=100). Those with cirrhosis (n=60) were randomly assigned 1:1 to the same regimen for either 12 (Arm B, n=31) or 24 weeks (Arm C, n=29). The primary efficacy endpoint was SVR12.

Approximately half of the patients were treatment-experienced, including 30% prior nulls, 13% prior relapsers, and 8% partial responders. A total of 19% reported a history of diabetes. 

SVR4 was achieved in 95% of patients in Arm A, 97% in Arm B, and 97% in Arm C. SVR12 was achieved in 94% of patients in Arm A, 97% in Arm B, and data is pending for Arm C. 

“The most common treatment-emergent adverse events were headache (36.9%), fatigue (31.9%), and pruritus (22.5%),” Dr. Esmat stated. One patient had a serious AE, deep venous thrombosis, that was “deemed reasonably possibly related to study drug.” No AEs led to treatment discontinuation; 1 patient withdrew consent (Arm A), and two met on-treatment criteria for virologic failure (Arm B, n=1; Arm C, n=1).

Study findings are “similar to the PEARL-I and AGATE-I studies in HCV GT4-infected patients receiving ombitasvir/paritaprevir/ritonavir with ribavirin,” Dr. Esmat concluded.