TY - JOUR
T1 - Randomised clinical trial: Alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II)
AU - Craxi, Antonio
AU - Van Kính, null
AU - Hsu, null
AU - Brass, Clifford A.
AU - Merz, null
AU - Flisiak, Robert
AU - Mazur, null
AU - Nault, null
AU - Calistru, null
AU - Merz, null
AU - Gould, null
AU - Thongsawat, null
AU - Griffel, Louis
AU - Abdurakhmanov, null
AU - Buggisch, Peter
AU - Makara, Mihály
AU - Mazur, null
AU - Mazzella, Giuseppe
AU - Vierling, John M
AU - Mutimer, David
AU - Naoumov, null
AU - Bao, null
AU - Samuel, Didier
AU - Zeuzem, Stefan
AU - Stanciu, null
AU - Heo, null
PY - 2015
Y1 - 2015
N2 - Background Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. Aim To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. Methods Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. Results A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. Conclusions Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens.
AB - Background Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. Aim To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. Methods Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. Results A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. Conclusions Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens.
KW - Adolescent; Adult; Aged; Antiviral Agents; Cyclosporine; Double-Blind Method; Drug Therapy
KW - Chronic; Humans; Interferon-alpha; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Treatment Outcome; United States; Young Adult
KW - Combination; Female; Genotype; Hepacivirus; Hepatitis C
KW - Adolescent; Adult; Aged; Antiviral Agents; Cyclosporine; Double-Blind Method; Drug Therapy
KW - Chronic; Humans; Interferon-alpha; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Treatment Outcome; United States; Young Adult
KW - Combination; Female; Genotype; Hepacivirus; Hepatitis C
UR - http://hdl.handle.net/10447/401609
UR - http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-2036
M3 - Article
VL - 42
SP - 829
EP - 844
JO - ALIMENTARY PHARMACOLOGY & THERAPEUTICS
JF - ALIMENTARY PHARMACOLOGY & THERAPEUTICS
SN - 0269-2813
ER -