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.
In this phase 3 trial, researchers have evaluated this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis.
In this multicenter, randomized, double-blind, placebo-controlled trial, 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 ( at a once-daily dose of 150 mg of ABT-450, 100 mg of Ritonavir, and 25 mg of Ombitasvir ), and Dasabuvir ( 250 mg twice daily ) with Ribavirin ( in doses determined according to body weight ) ( group A ) or matching placebos ( group B ).
The patients received the study treatment during a 12-week double-blind period.
The primary end point was sustained virologic response at 12 weeks after the end of treatment. The primary analysis compared the response rate in group A with the response rate ( 78% ) 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 A and group B.
A total of 631 patients received at least one dose of the study drugs. The rate of sustained virologic response in group A was 96.2% ( 95% confidence interval, 94.5 to 97.9 ), which was superior to the historical control rate.
Virologic failure during treatment and relapse after treatment occurred in 0.2% and 1.5%, respectively, of the patients in group A.
The response rates in group A were 95.3% among patients with HCV genotype 1a infection and 98.0% 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 A than in group B ( P less than 0.05 for all comparisons ).
Reductions in the hemoglobin level were all of grade 1 or 2; reductions of grade 1 and 2 occurred in 47.5% and 5.8%, respectively, of the patients in group A, whereas grade 1 reductions occurred in 2.5% of the patients in group B.
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. ( Xagena )
Feld JJ et al, NEJM 2014; Epub ahead of print