Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca
1827. Daclatasvir Combined With Peginterferon Alfa-2a and Ribavirin for 12 or 16 Weeks in Patients With Hepatitis C Virus Genotype 2 or 3 Infection: COMMAND GT 2/3 Study
Session: Oral Abstract Session: Hepatitis C
Saturday, October 5, 2013: 2:30 PM
Room: The Moscone Center: 250-262
Background: Daclatasvir (DCV) is a first-in-class NS5A replication complex inhibitor, active against HCV genotype (GT)1-6 in vitro. Study AI444-031 evaluated DCV 60mg QD + peginterferon-alfa-2a (peg-alfa) 180mcg weekly and ribavirin (RBV) 400mg BID for 12 or 16 weeks in patients with chronic HCV GT2 or GT3 infection.
Methods: Adult treatment-naïve patients were randomly assigned to DCV/peg-alfa/RBV for 12 or 16 weeks or placebo/peg-alfa/RBV for 24 weeks. DCV/peg-alfa/RBV recipients without protocol-defined response (PDR; HCV RNA <LLOQ week-4 and undetectable week-10) discontinued DCV at week 12 and received 12 additional weeks of peg-alfa/RBV. The primary efficacy endpoint was SVR24.
Results: Baseline characteristics were well-balanced in the DCV 12-week (N=50), DCV 16-week (N=50) and placebo (N=51) arms; more patients with GT3 (18/80, 22.5%) than GT2 (1/71, 1.4%) were cirrhotic. 78%-88% of DCV recipients achieved PDR. SVR24 rates were higher in GT2 than GT3 with all regimens; within each genotype, SVR24 rates were similar in DCV arms and higher than placebo/peg-alfa/RBV. In DCV arms, one GT2 and 12 GT3 patients relapsed. In GT3, relapse was higher among cirrhotics (3/7, 43%) than non-cirrhotics (3/19, 16%) in the 12-week arm but similar in the 16-week arm (1/4, 25% vs 5/20, 25%). There were 7 on-treatment serious AEs (DCV, 4; placebo, 3); no deaths. AEs were typical of those associated with peg-alfa/RBV.
Conclusion: Shorter treatment duration (12 or 16 weeks) with DCV/peg-alfa/RBV demonstrated higher SVR rates than 24 weeks of peg-alfa/RBV in patients with GT2 or GT3 infection, with higher SVR rates in GT2 with all regimens. These results support further evaluation of DCV-containing regimens for different HCV genotypes.
| GT 2 | GT 3 | |||||
| Response, n (%) | DCV | DCV | PBO
(N=24) | DCV
(N=26) | DCV
(N=27) | PBO
(N=27) |
| Protocol-defined response | 21 (88) | 18 (78) | - | 22 (85) | 22 (82) | - |
| End of treatment response (HCV RNA undetectable) | 23 (96) | 21 (91) | 22 (92) | 25 (96) | 24 (89) | 21 (78) |
| SVR12 (HCV RNA <LLOQ 12 weeks posttreatment) | 21 (88) | 19 (83) | 17 (71) | 18 (69) | 21 (78) | 14 (52) |
| SVR24 (HCV RNA undetectable 24 weeks posttreatment)* | 20 (83) | 19 (83) | 15 (63) | 18 (69) | 18 (67) | 16 (59) |
| *Failure to achieve SVR reflects relapse or missing data at posttreatment week 24 | ||||||
Gregory Dore1, Eric Lawitz2, Christophe Hezode3, Stephen Shafran, MD4, Alnoor Ramji5, Harvey Tatum6, Gloria Taliani7, Albert Tran8, Maurizia Brunetto9, Serena Zaltron10, Simone Strasser11, Nina Weis12, Wayne Ghesquiere13, Samuel Lee14, Dominique Larrey15, Stanislas Pol16, Hugh Harley17, Jacob George18, Scott Fung19, Victor De Ledinghen20, Peggy Hagens21, David Cohen22, Elizabeth Cooney22, Stephanie Noviello22 and Eric Hughes23, (1)University of New South Wales and St Vincent's Hospital, Darlinghurst, Australia, (2)Texas Liver Insititute, University of Texas Health Science Center, San Antonio, TX, (3)Hopital Henri Mondor, Creteil, France, (4)University of Alberta, Edmonton, AB, Canada, (5)University of British Columbia, Gastrointestinal Research Institute, Vancouver, BC, Canada, (6)Options Health Research, Tulsa, OK, (7)Azienda Ospedaliera Universitaria, Policlinico Umberto I, Roma, Italy, (8)Hopital De L'Archet 2, Nice Cedex 03 Na, France, (9)Unita Operativa Gastroenterologia Ed Epatologia, Pisa, Italy, (10)Azienda Ospedaliera Spedali Civili di Brescia, Province of Brescia, Italy, (11)Royal Prince Alfred Hospital, Camperdown, Australia, (12)Copenhagen University Hospital, Hvidovre, Denmark, (13)Vancouver Island Health Authority, Victoria, BC, Canada, (14)Heritage Medical Research Clinic, University of Calgary, Calgary, AB, Canada, (15)Hôpital Saint-Eloi, Montpellier cedex 5, France, (16)Université Paris Descartes, INSERM U1610 and Liver Unit, Hôpital Cochin, Paris, France, (17)Royal Adelaide Hospital, Adelaide, Australia, (18)Westmead Hospital, Sydney, Australia, (19)Toronto General Hospital, Toronto, ON, Canada, (20)Hopital Haut-Leveque, Pessac, France, (21)Bristol-Myers Squibb, Braine-l’Alleud, Belgium, (22)Bristol-Myers Squibb, Wallingford, CT, (23)Bristol-Myers Squibb, Princeton, NJ
Disclosures:
G. Dore, Bristol-Myers Squibb: Investigator, Research support
E. Lawitz, Bristol-Myers Squibb: Investigator, Research support
C. Hezode, Bristol-Myers Squibb: Investigator, Research support
S. Shafran, Bristol-Myers Squibb: Investigator, Research support
A. Ramji, Bristol-Myers Squibb: Investigator, Research support
H. Tatum, Bristol-Myers Squibb: Investigator, Research support
G. Taliani, Bristol-Myers Squibb: Investigator, Research support
A. Tran, Bristol-Myers Squibb: Investigator, Research support
M. Brunetto, Bristol-Myers Squibb: Investigator, Research support
S. Zaltron, Bristol-Myers Squibb: Investigator, Research support
S. Strasser, Bristol-Myers Squibb: Investigator, Research support
N. Weis, Bristol-Myers Squibb: Investigator, Research support
W. Ghesquiere, Bristol-Myers Squibb: Investigator, Research support
S. Lee, Bristol-Myers Squibb: Investigator, Research support
D. Larrey, Bristol-Myers Squibb: Investigator, Research support
S. Pol, Bristol-Myers Squibb: Investigator, Research support
H. Harley, Bristol-Myers Squibb: Investigator, Research support
J. George, Bristol-Myers Squibb: Investigator, Research support
S. Fung, Bristol-Myers Squibb: Investigator, Research support
V. De Ledinghen, Bristol-Myers Squibb: Investigator, Research support
P. Hagens, Bristol-Myers Squibb: Employee, Salary
D. Cohen, Bristol-Myers Squibb: Employee, Salary
E. Cooney, Bristol-Myers Squibb: Employee, Salary
S. Noviello, Bristol-Myers Squibb: Employee, Salary
E. Hughes, Bristol-Myers Squibb: Employee, Salary
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