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Aliment Pharmacol Ther. 2015 Oct;42(7):829-44. doi: 10.1111/apt.13342. Epub 2015 Aug 4.

Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II).

Collaborators (156)

Tanno H, Bessone F, Terg R, Frider B, Bertuzzi R, Desmond P, Zekry A, Weltman M, George J, Crawford D, Matthews G, Moreno C, Van Vlierberghe H, Reynaert H, Gould M, Lee S, Ramji A, Tam E, Marotta P, Yoshida E, Wong F, Feld J, Samuel D, Marcellin P, Alric L, Zarski JP, Zoulim F, Buggisch P, Hinrichsen H, Goeser T, Zeuzem S, Galle P, Berg T, Schott E, Rasenack J, Gerken G, Wedemeyer H, Tsang O, Yuen MF, Chan H, Hui AJ, Makara M, Tornai I, Gervain J, Szalay F, Varga M, Horvath G, Hunyady B, Vincze A, Mazzella G, Gaeta GB, Alberti A, Colombo M, Andreone P, Rizzetto M, Angelico M, Craxi A, Picciotto A, Sacchi P, Vinci M, Invernizzi P, Bruno S, Heo J, Lee Y, Cho M, Han S, Lee J, Ahn S, Lim Y, Hwang S, Sanchez J, Muñoz L, Maldonado H, Mazur W, Flisiak R, Jablkowski M, Kryczka W, Halota W, Calistru P, Prelipcean C, Musa M, Stanciu C, Manuc M, Tanasescu C, Dumitrascu D, Abdurakhmanov D, Chulanov V, Nikitin I, Zhdanov K, Esaulenko E, Maevskaya M, Znoyko O, Lamoglia RS, Ferret MB, Garcia-Samaniego J, Gomez MR, Diago M, Calleja JL, Hsu SJ, Chuang WL, Hu TH, Peng CY, Chen CY, Kao JH, Thongsawat S, Sukeepaisarnjaroen W, Piratvisuth T, Tanwandee T, Komolmit P, Agarwal K, Mutimer D, Brown A, Foster G, McPherson S, Ryder S, Poulos J, Rustgi V, Lyche K, Omarro S, Vierling J, Ghalib R, Karnam U, Peine C, Galati J, Person J, De La Torre A, Ravendhran N, Mushahwar A, O'Leary J, Lee W, Lawitz E, Ankoma-Sey V, King J, Pound D, Scarsella A, Thuluvath P, Pockros P, Mailliard M, Shiffman M, Sylvestre D, Heiman D, Jacobson I, Bacon B, Dimitroff J, Reindollar R, Tobias H, Godofsky E, Rodriguez-Torres M, Bennett M, Ben-Zvi J, Van KN, Dao L, Huu HB, Minh YL, Le Thanh L, Van Long D.

Author information

1
Frankfurt, Germany.
2
Bialystok, Poland.
3
Houston, TX, USA.
4
Chorzów, Poland.
5
Bologna, Italy.
6
Chiang Mai, Thailand.
7
Moscow, Russia.
8
Hanoi, Viet Nam.
9
Bucharest, Romania.
10
Busan, Republic of Korea.
11
Iasi, Romania.
12
Toronto, ON, Canada.
13
Budapest, Hungary.
14
Yunlin County, Taiwan.
15
Hamburg, Germany.
16
Villejuif, France.
17
Birmingham, UK.
18
Novartis Pharma AG, Basel, Switzerland.
19
Novartis Institutes for BioMedical Research, Basel, Switzerland.
20
Novartis Pharmaceuticals, East Hanover, NJ, USA.

Abstract

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.

PMID:
26238707
DOI:
10.1111/apt.13342
[Indexed for MEDLINE]
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