Alisporivir with peginterferon/ribavirin in patients with chronic hepatitis C genotype 1 infection who failed to respond to or relapsed after prior interferon-based therapy: FUNDAMENTAL, a Phase II trial

Journal of Viral Hepatitis

Volumn 22, Issue 7, 2015, Pages 596-606

  Buti, M ^a   Flisiak, R ^b   Kao, J H ^c   Chuang, W L ^d   Streinu Cercel, A ^e   Tabak, F ^f   Calistru, P ^g   Goeser, T ^h   Rasenack, J ⁱ   Horban, A ^j   Davis, G L ^k   Alberti, A ^l   Mazzella, G ^m   Pol, S ⁿ   Orsenigo, R ^o   Brass, C ^o  

^a HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^b MEDICAL UNIVERSITY OF BIALYSTOK   (Poland)

^c NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^d KAOHSIUNG MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

^e CAROL DAVILA UNIVERSITY OF MEDICINE AND PHARMACY   (Romania)

^f ISTANBUL UNIVERSITY   (Turkey)

^g Centrul de Diagnostic Si Tratament Dr Viktor Babeş ^*  (Romania)

^h UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

ⁱ UNIVERSITY OF FREIBURG   (Germany)

^j MEDICAL UNIVERSITY OF WARSAW   (Poland)

^k BAYLOR UNIVERSITY MEDICAL CENTER   (United States)

^l UNIVERSITY OF PADOVA   (Italy)

^m UNIVERSITY OF BOLOGNA   (Italy)

ⁿ Hôpital Cochin ^*  (France)

^o NOVARTIS PHARMA AG   (Switzerland)

more..

Author keywords

alisporivir; antiviral therapy; genotype 1; hepatitis C virus; host targeting agent

Indexed keywords

ALISPORIVIR; PEGINTERFERON ALPHA2A; PLACEBO; RIBAVIRIN; ALPHA INTERFERON; ANTIVIRUS AGENT; CYCLOSPORIN;

ADULT; AGED; ANEMIA; ARTICLE; ASTHENIA; CHRONIC HEPATITIS C; CLINICAL EFFECTIVENESS; CONTROLLED STUDY; COUGHING; DECREASED APPETITE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG FATALITY; DRUG RESPONSE; DRUG SAFETY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; FATIGUE; FEMALE; FEVER; GENOTYPE; HEADACHE; HEPATITIS C VIRUS GENOTYPE 1; HUMAN; HYPERBILIRUBINEMIA; HYPERTENSION; HYPERTRIGLYCERIDEMIA; INSOMNIA; LIVER CIRRHOSIS; LIVER FIBROSIS; MAJOR CLINICAL STUDY; MALE; NAUSEA; NEUTROPENIA; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RELAPSE; THROMBOCYTOPENIA; TREATMENT DURATION; ADVERSE EFFECTS; CLINICAL TRIAL; DRUG COMBINATION; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; HEPATITIS C, CHRONIC; MIDDLE AGED; MULTICENTER STUDY; PATHOLOGY; PROCEDURES; SALVAGE THERAPY; TREATMENT OUTCOME; VIRUS LOAD; YOUNG ADULT;

ADULT; AGED; ANTIVIRAL AGENTS; CYCLOSPORINE; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; FEMALE; HEPATITIS C, CHRONIC; HUMANS; INTERFERON-ALPHA; MALE; MIDDLE AGED; PLACEBOS; RIBAVIRIN; SALVAGE THERAPY; TREATMENT OUTCOME; VIRAL LOAD; YOUNG ADULT;

EID: 84930332667     PISSN: 13520504     EISSN: 13652893     Source Type: Journal    
DOI: 10.1111/jvh.12360     Document Type: Article

References (27)

1. World Health Organization. Hepatitis C. Fact sheet N°164; April 2014. Available at: http://www.who.int/mediacentre/factsheets/fs164/en/ (accessed April 2014).
2. Casey LC, Lee WM,. Hepatitis C virus therapy update 2013. Curr Opin Gastroenterol 2013; 29: 243-249.
3. Laing TJ, Ghany MG,. Current and future therapies for hepatitis C virus infection. N Engl J Med 2013; 368: 1907-1917.
4. Streinu-Cercel A,. Hepatitis C in the interferon-free era. Germs 2013; 3: 114.
5. Manns MP, McHutchison JG, Gordon SC, et al,. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001; 358: 958-965.
6. Fried MW, Shiffman ML, Reddy KR, et al,. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347: 975-982.
7. McHutchison JG, Lawitz EJ, Shiffman ML, et al,. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 2009; 361: 580-593.
8. Coelmont L, Hanoulle X, Chatterji U, et al,. DEB025 (Alisporivir) inhibits hepatitis C virus replication by preventing a cyclophilin A induced cis-trans isomerisation in domain II of NS5A. PLoS ONE 2010; 5: e13687.
9. Landrieu I, Hanoulle X, Bonachera F, et al,. Structural basis for the non-immunosuppressive character of the cyclosporin A analogue Debio 025. Biochemistry 2010; 49: 4679-4686.
10. Gallay PA, Lin K,. Profile of alisporivir and its potential in the treatment of hepatitis C. Drug Des Devel Ther 2013; 7: 105-115.
11. Flisiak R, Feinman SV, Jablkowski M, et al,. The cyclophilin inhibitor Debio 025 combined with PEG IFNalpha2a significantly reduces viral load in treatment-naïve hepatitis C patients. Hepatology 2009; 49: 1460-1468.
12. Flisiak R, Pawlotsky JM, Crabbe R, et al,. Once daily alisporivir (DEB025) plus peg-IFN-alfa-2a/ribavirin results in superior sustained virologic response (SVR24) in chronic hepatitis C genotype 1 treatment-naïve patients-the ESSENTIAL study. J Hepatol 2011; 55. Abstract 190.
13. Pawlotsky JM, Sarin SK, Foster GR, et al,. Alisporivir plus ribavirin achieves high rates of sustained HCV clearance (SVR24) as interferon (IFN)-free or IFN-add-on regimen in treatment-naïve patients with HCV GT2 or GT3 patients: final results from the VITAL-1 study. Hepatology 2012; 56 (Suppl. 4): 309A.
14. Poynard T, Colombo M, Bruix J, et al,. Peginterferon alfa-2b and ribavirin: effective in patients with hepatitis C who failed interferon alfa/ribavirin therapy. Gastroenterology 2009; 136: 1618-1628.
15. Wang W, Mehrota I, Chan S, Heyse J,. Statistical considerations for noninferiority/equivalence trials in vaccine development. J Biopharm Stat 2006; 16: 429-441.
16. Bacon BR, Gordon SC, Lawitz E, et al,. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1207-1217.
17. Zeuzem S, Andreone P, Pol S, et al,. Telaprevir for retreatment of HCV infection. N Engl J Med 2011; 364: 2417-2428.
18. Zeuzem S, Berg T, Gane E, et al,. Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial. Gastroenterology 2014; 146: 430-441.
19. Griffel L, Bao W, Orsenigo R, et al,. Interferon (IFN)-free alisporivir (ALV) has a better overall safety profile compared to IFN-containing treatment: a pooled analysis of the ALV development program. J Hepatol 2013; 58 (Suppl. 1): S336-S337.
20. Chaudhari S, Park J, Anand BS, et al,. Acute pancreatitis associated with interferon and ribavirin therapy in patients with chronic hepatitis C. Dig Dis Sci 2004; 49: 1000-1006.
21. da Sila J, Giroldi SB, de Oliveira Basso F, et al,. Acute pancreatitis during interferon-alpha and ribavirin treatment for hepatitis C. BMJ Case Rep 2009; pii: bcr09.2008.0998. doi: 10.1136/bcr.09.2008.0998. Epub 2009 Mar 20.
22. Ando K, Kim SR, Imoto S, et al,. Acute pancreatitis associated with pegylated interferon and ribavirin treatment of chronic hepatitis C, genotype 1b with high viral load. Case Rep Gastroenterol 2009; 3: 372-376.
23. Drug-induced pancreatitis. Pharmacist's Letter/Prescriber's Letter. April 2013.
24. Griffel L, Bao W, Orsenigo R, et al,. Interferon (IFN)-free alisporivir (DEB025) treatment in the VITAL-1 study has a more beneficial overall safety profile vs IFN-containing treatment. Hepatology 2012; 56 (Suppl. 4): 578A.
25. Lange CM, Zeuzem S,. Perspectives and challenges of interferon-free therapy for chronic hepatitis C. J Hepatol 2012; 58: 583-592.
26. American Association for the Study of Liver Diseases (AASLD)/Infectious Diseases Society of America (IDSA). Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view (accessed February 2014).
27. Chatterji U, Garcia-Rivera JA, Baugh J, et al,. The combination of alisporivir plus an NS5A inhibitor provides additive to synergistic anti-hepatitis C virus activity without detectable cross resistance. Antimicrob Agents Chemother 2014; 58: 3327-3334.