The interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r) and the NS5A inhibitor ombitasvir (also known as ABT-267) plus the nonnucleoside polymerase inhibitor dasabuvir (also known as ABT-333) and ribavirin has shown efficacy against the hepatitis C virus (HCV) in patients with HCV genotype 1 infection.
Dr Jordan Feld and colleagues performed a phase 3 trial to evaluate this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis.
In this multicenter, randomized, double-blind, placebo-controlled trial, the researchers assigned previously untreated patients with HCV genotype 1 infection, in a 3:1 ratio, to an active regimen consisting of a single-tablet coformulation of ABT-450/r–ombitasvir, and dasabuvir with ribavirin (Group 1) or matching placebos (Group 2).
The patients received the study treatment during a 12-week double-blind period.
The researcher's primary end point was sustained virologic response at 12 weeks after the end of treatment.
|The rate of sustained virologic response in Group 1 was 96%|
|New England Journal of Medicine|
The primary analysis compared the response rate in Group 1 with the response rate in a historical control group of previously untreated patients without cirrhosis who received telaprevir with peginterferon and ribavirin.
Adverse events occurring during the double-blind period were compared between Group 1 and Group 2.
The team reported that a total of 631 patients received at least one dose of the study drugs.
The rate of sustained virologic response in Group 1 was 96%, which was superior to the historical control rate.
The research team noted that virologic failure during treatment and relapse after treatment occurred in 0.2% and 1.5%, respectively, of the patients in Group 1.
The team found that response rates in Group 1 were 95% among patients with HCV genotype 1a infection, and 98% among those with HCV genotype 1b infection.
The rate of discontinuation due to adverse events was 0.6% in each study group.
Nausea, pruritus, insomnia, diarrhea, and asthenia occurred in significantly more patients in Group 1 than in Group 2.
The researchers observed that reductions in the hemoglobin level were all of grade 1 or 2.
The team noted that reductions of grade 1 and 2 occurred in 48% and 6%, respectively, of the patients in Group 1, whereas grade 1 reductions occurred in 3% of the patients in Group 2.
Dr Feld's team concludes, "In previously untreated patients with HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of ABT-450/r–ombitasvir and dasabuvir with ribavirin was highly effective and was associated with a low rate of treatment discontinuation."