studies

732A AASLD ABSTRACTS HEPATOLOGY, October, 2015
In these patients, rare mutations in NS5A region, R30H, A92K,
P29del and P32del, were detected simultaneously with NS3-
D168E/V mutations in HCV straines obtained at virologic failure.
Especially in 2 patients showing null-response, P29del
and P32del mutations were found, and experiments using replicon
system revealed HCV strains with such deletions showed
>390,000-fold registance against DCV. Consequently, SVR4-
12 rates in patients without baseline Y93H mutation were 95%
when those receiving SMV were excluded. Deep-sequencing
to evaluate the kinetics of HCV strains with P29del and P32del
was currently in progress. Conclusion: Although high SVR rates
were obtained after DCV/ASV therapy in patients without
baseline NS5A-RAVs, rare RAVs extremely resistant to NS5A
inhibitors emerged frequently in those receiving SMV previously.
Such patients should be add to the lists of contraindication
for DCV/ASV therapy even when baseline NS5A-RAVs
were absent.
Disclosures:
Yoshihito Uchida - Patent Held/Filed: SRL Inc.
Jun-ichi Kouyama - Patent Held/Filed: SRL Inc.
Kayoko Naiki - Patent Held/Filed: SRL Inc.
Satoshi Mochida - Grant/Research Support: Chugai, MSD, Tioray Medical,
BMS; Speaking and Teaching: MSD, Toray Medical, BMS, Tanabe Mitsubishi
The following authors have nothing to disclose: Nobuaki Nakayama, Hayato
Uemura, Kayoko Sugawara, Mie Inao
pts without cirrhosis received 12 weeks (wks) of 3D+RBV and
cirrhotics received 12 or 24 wks of 3D+RBV. GT1b-infected
pts without cirrhosis received 12 wks of 3D and cirrhotics
received 12 wks of 3D+RBV. End of treatment response (EOTR)
is reported; SVR12 will be presented. Results: 615 pts enrolled
and received study drug. Baseline characteristics and treatment
response are presented below. 98.0% (603/615) of pts
achieved EOTR. 0.8% (5/615) of pts experienced on-treatment
virologic failure, and 1.0% (6/615) discontinued treatment
due to adverse events. The most common adverse events
(occurring in >10% of pts) were fatigue, nausea, headache,
insomnia, and pruritus. Serious adverse events considered at
least possibly related to 3D treatment were reported in 0.5%
(3/615) of pts. Conclusions: In the TOPAZ-II study, 3D+/-RBV
achieved high rates of on-treatment response and has been
well-tolerated with a low rate of discontinuation due to adverse
events in a broad population of HCV GT1-infected pts.
Baseline characteristics and efficacy
1065
Preliminary Safety and Efficacy Results from TOPAZ-II:
A Phase 3b Study Evaluating Long-Term Clinical Outcomes
in HCV Genotype 1-infected Patients Receiving
Ombitasvir/Paritaprevir/r and Dasabuvir +/-Ribavirin
Nancy Reau 1 , Fred Poordad 2 , Jeffrey Enejosa 3 , Asma Siddique 4 ,
Humberto I. Aguilar 5 , Jacob P. Lalezari 6 , Franco Felizarta 7 , Peter
J. Ruane 8 , Peter Varunok 9 , David Bernstein 10 , Douglas Dieterich 11 ,
Gregory T. Everson 12 , Yiran Hu 3 , Greg Ball 3 , Tami Pilot-Matias 3 ,
Nancy Shulman 3 , Sanjeev Arora 13 ; 1 University of Chicago Medical
Center, Chicago, IL; 2 The Texas Liver Institute/University of
Texas Health Science Center, San Antonio, TX; 3 AbbVie Inc.,
North Chicago, IL; 4 Virginia Mason Medical Center, Seattle, WA;
5 Louisiana Research Center, LLC, Shreveport, LA; 6 Quest Clinical
Research, San Francisco, CA; 7 Private practice, Bakersfield, CA;
8 Ruane Medical and Liver Health Institute, Los Angeles, CA; 9 Premier
Medical Group of the Hudson Valley, PC, Poughkeepsie, NY;
10 North Shore University Hospital, Manhasset, NY; 11 Mount Sinai
School of Medicine, Icahn School of Medicine, New York, NY;
12 University of Colorado Denver School of Medicine, Aurora, CO;
13 University of New Mexico, Albuquerque, NM
Background: The 3-direct-acting antiviral regimen of ombitasvir/paritaprevir/ritonavir
(paritaprevir identified by AbbVie
and Enanta, co-dosed with ritonavir) and dasabuvir (3D) +/-ribavirin
(RBV) has resulted in high SVR12 rates with a favorable
safety profile in HCV genotype (GT) 1-infected patients (pts),
including those with compensated cirrhosis, in phase 3 trials.
TOPAZ-I (ex-US) and TOPAZ-II (US) are evaluating the impact
of SVR12 on progression of liver disease through 5 years
post-treatment in a broad population of HCV GT1-infected pts
receiving 3D+/-RBV. Here, we report on-treatment safety and
efficacy of 3D+/-RBV among pts in the TOPAZ-II study. Methods:
TOPAZ–II is a phase 3b, open-label, non-randomized,
multicenter trial conducted in 48 community and academic
centers in the US. Pts are treatment-naïve or interferon/RBV
treatment-experienced, with or without compensated cirrhosis.
There was no upper limit on age, BMI, or ALT/AST levels. Pts
with creatinine clearance ≥30 mL/min, albumin ≥2.8 g/dL,
and platelet count ≥25 × 10 9 /L were eligible. GT1a-infected
*Data missing for 1 pt
Disclosures:
Nancy Reau - Advisory Committees or Review Panels: Jannsen, Merck, AbbVie,
Intercept, Salix, BMS, Jannsen; Grant/Research Support: Merck, Gilead, BMS,
AbbVie, Jannsen, BI
Fred Poordad - Advisory Committees or Review Panels: Abbott/Abbvie, Achillion,
BMS, Inhibitex, Boeheringer Ingelheim, Pfizer, Genentech, Idenix, Gilead,
Merck, Vertex, Salix, Janssen, Novartis; Grant/Research Support: Abbvie,
Anadys, Achillion, BMS, Boehringer Ingelheim, Genentech, Idenix, Gilead,
Merck, Pharmassett, Vertex, Salix, Tibotec/Janssen, Novartis
Jeffrey Enejosa - Employment: AbbVie; Stock Shareholder: AbbVie
Humberto I. Aguilar - Speaking and Teaching: abbvie, gilead
Franco Felizarta - Grant/Research Support: AbbVie, Gilead, Janssen, Merck,
BMS, Boehringer-Ingelheim, Vertex, Roche; Speaking and Teaching: AbbVie,
Gilead, Janssen, Merck
Peter J. Ruane - Advisory Committees or Review Panels: Gilead, Boehringer,
Jannsen, Viiv, Abbott; Consulting: Gilead, Jannsen, Abbott, BMS; Grant/
Research Support: Gilead, Boehringer, Jannsen, Idenix, Abbott, BMS; Speaking
and Teaching: Gilead, Merck, Boehringer, Jannsen, VIIV, Abbott, BMS; Stock
Shareholder: Gilead
David Bernstein - Advisory Committees or Review Panels: Gilead; Consulting:
Abbvie, BMS, Merck, Janssen; Grant/Research Support: Gilead, Abbvie, BMS,
Merck, Janssen, Genentech; Speaking and Teaching: Abbvie, BMS, Merck,
Gilead
Douglas Dieterich - Advisory Committees or Review Panels: Gilead, BMS, Abbvie,
Janssen, Merck, Achillion
Gregory T. Everson - Advisory Committees or Review Panels: Roche/Genentech,
Abbvie, Galectin, Boehringer-Ingelheim, Eisai, Bristol-Myers Squibb, HepC
Connection, BioTest, Gilead, Merck; Board Membership: HepQuant LLC, PSC
Partners, HepQuant LLC; Consulting: Abbvie, BMS, Gilead, Bristol-Myers Squibb;
Grant/Research Support: Roche/Genentech, Pharmassett, Vertex, Abbvie, Bristol-Myers
Squibb, Merck, Eisai, Conatus, PSC Partners, Vertex, Tibotec, GlobeImmune,
Pfizer, Gilead; Management Position: HepQuant LLC, HepQuant LLC;
Patent Held/Filed: Univ of Colorado; Speaking and Teaching: Abbvie, Gilead
Yiran Hu - Employment: AbbVie Inc.
Tami Pilot-Matias - Employment: AbbVie; Stock Shareholder: AbbVie
Nancy Shulman - Employment: Abbvie
The following authors have nothing to disclose: Asma Siddique, Jacob P. Lalezari,
Peter Varunok, Greg Ball, Sanjeev Arora