Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis

Abstract

GIFT-I is a phase 3 trial evaluating the efficacy and safety of a 12-week regimen of coformulated ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) for treatment of Japanese hepatitis C virus genotype 1b-infected patients. It consists of a double-blind, placebo-controlled substudy of patients without cirrhosis and an open-label substudy of patients with compensated cirrhosis. Patients without cirrhosis were randomized 2:1 to once-daily OBV/PTV/r (25 mg/150 mg/100 mg; group A) or placebo (group B). Patients with cirrhosis received open-label OBV/PTV/r (group C). The primary efficacy endpoint was the rate of sustained virological response 12 weeks posttreatment in interferon-eligible, treatment-naive patients without cirrhosis and hepatitis C virus RNA ≥100,000 IU/mL in group A. A total of 321 patients without cirrhosis were randomized and dosed with double-blind study drug (106 received double-blind placebo and later received open-label OBV/PTV/r), and 42 patients with cirrhosis were enrolled and dosed with open-label OBV/PTV/r. In the primary efficacy population, the rate of sustained virological response 12 weeks posttreatment was 94.6% (106/112, 95% confidence interval 90.5-98.8). Sustained virological response 12 weeks posttreatment rates were 94.9% (204/215) in group A, 98.1% (104/106) in group B (open-label), and 90.5% (38/42) in group C. Overall, virological failure occurred in 3.0% (11/363) of patients who received OBV/PTV/r. The rate of discontinuation due to adverse events was 0%-2.4% in the three patient groups receiving OBV/PTV/r. The most frequent adverse event in patients in any group was nasopharyngitis.

Conclusion: In this broad hepatitis C virus genotype 1b-infected Japanese patient population with or without cirrhosis, treatment with OBV/PTV/r for 12 weeks was highly effective and demonstrated a favorable safety profile.

Figure 1

GIFT‐I study design. *Randomization was 2:1 to groups A and B. Abbreviations: DB, double‐blind; OL, open‐label.

Figure 2

SVR12 rates. Error bars represent 95% CIs calculated by normal approximation to the binomial for the primary efficacy population and by Wilson score method for all others. The threshold of 63% (based on the historical telaprevir‐based SVR rate) to which the SVR12 rate for the primary efficacy population was compared is marked with a horizontal line in the first column. The primary efficacy population was composed of patients randomized to group A who received study drug and who were treatment‐naive without cirrhosis, were IFN‐eligible, and had HCV RNA ≥100,000 IU/mL. Abbreviations: DB, double‐blind; OL, open‐label.