studies

338A AASLD ABSTRACTS HEPATOLOGY, October, 2015
D (n=30), E (n=29), F (n=31), or G (n=30). Subjects were
male, 56%; median age, 52.0 years; GT3a, 98%; TN, 92%;
TE, 8%; fibrosis >F2, 15%; median baseline HCV RNA log 10
IU/mL, 6.7. There has been 1 virologic failure thus far in each
treatment arm (n=4), 3 of which were in pegIFN/RBV TE subjects.
One subject in Arm G was lost to follow-up at the week
2 visit. The SVR4 rate was 96% (27/28), 96% (27/28), 97%
(29/30) and 93% (27/29) in Arms D, E, F, and G, respectively,
among subjects with available post-treatment Week 4
data. AEs were mostly mild, with most common DAA-related
AEs being fatigue, nausea, and headache. There were no serious
DAA-related AEs; 1 subject discontinued due to DAA- and
RBV-related AEs of abdominal pain and heat sensation. Typical
reductions in hemoglobin were observed in the RBV containing
arm (Arm F). Conclusions: ABT-493+ABT-530 treatment for
12 weeks with or without RBV in TN or TE noncirrhotic HCV
GT3-infected subjects was well tolerated. Promising SVR4 rates
of 93%–96% were achieved without RBV. SVR12 data and
further details regarding virologic failures will be available
at the time of the meeting. These encouraging results warrant
further study of this once-daily ABT-493/ABT-530 regimen in
GT3 patients, including patients with cirrhosis.
Disclosures:
Paul Y. Kwo - Advisory Committees or Review Panels: Abbvie, Abbott, Novartis,
Merck, Gilead, BMS, Janssen; Consulting: BMS; Grant/Research Support:
Roche, Abbvie, Merck, BMS, Abbott, Idenix, Vital Therapeutics, Gilead, Vertex,
Merck, Idenix; Speaking and Teaching: Merck, Merck
Stanley Wang - Employment: AbbVie
David L. Wyles - Advisory Committees or Review Panels: Bristol Myers Squibb,
Janssen, Merck; Grant/Research Support: Gilead, Merck, Bristol Myers Squibb,
AbbVie, Tacere
Peter J. Ruane - Advisory Committees or Review Panels: BMS; Consulting: Gilead,
Abbvie, Janssen; Grant/Research Support: BMS, Gilead, Merck, Abbvie, Idenix,
Idenix, Janssen, Viiv; Speaking and Teaching: Gilead, Merck, Abbvie, Abbvie,
Janssen; Stock Shareholder: Gilead, Gilead
Benedict Maliakkal - Speaking and Teaching: Valeant Pharma (Salix), Gilead,
AbbVie, Bristol Myers Squibb
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
Ran Liu - Employment: Abbvie
Chih-Wei Lin - Employment: Abbvie
Teresa Ng - Employment: AbbVie; Patent Held/Filed: AbbVie; Stock Shareholder:
AbbVie
Federico J. Mensa - Employment: Abbvie Inc.; Stock Shareholder: Abbvie Inc.
Jens Kort - Employment: AbbVie Inc.; Stock Shareholder: AbbVie Inc.
The following authors have nothing to disclose: Michael Bennett, Hugo E. Vargas,
J. Scott Overcash, Asma Siddique, Bal R. Bhandari
249
Sofosbuvir/GS-5816 Fixed Dose Combination for 12
Weeks Compared to Sofosbuvir with Ribavirin for 24
Weeks in Genotype 3 HCV Infected Patients: The Randomized
Controlled Phase 3 ASTRAL-3 Study
Alessandra Mangia 1 , Stuart K. Roberts 2 , Stephen Pianko 3 , Alex
J. Thompson 4 , Curtis Cooper 5 , Brian Conway 6 , Marc Bourlière
7 , Tarik Asselah 8 , Thomas Berg 9 , Stefan Zeuzem 10 , William
M. Rosenberg 11 , Kosh Agarwal 12 , Edward J. Gane 13 , Catherine
A. Stedman 14 , Francesco Mazzotta 15 , Tram T. Tran 16 , Stuart
C. Gordon 17 , Evguenia S. Svarovskaia 18 , Lingling Han 18 ,
John McNally 18 , Anu Osinusi 18 , Diana M. Brainard 18 , John G.
McHutchison 18 , Nezam H. Afdhal 19 , Graham R. Foster 20 ; 1 Casa
Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy;
2 Alfred Health and Monash University, Melbourne, VIC, Australia;
3 Monash Health and Monash University, Melbourne, VIC, Australia;
4 St Vincent’s Hospital, Melbourne, VIC, Australia; 5 Ottawa
General Hospital, Ottawa, ON, Canada; 6 Vancouver Infectious
Diseases Centre, Vancouver, BC, Canada; 7 Hôpital Saint Joseph,
Marseilles, France; 8 University Paris Diderot, INSERM U773, Paris,
France; 9 University Hospital Leipzig, Leipzig, Germany; 10 Johann
Wolfgang Goethe University, Frankfurt, Germany; 11 University
College London, London, United Kingdom; 12 Kings College
Hospital, London, United Kingdom; 13 Auckland Clinical Studies,
Auckland, New Zealand; 14 Christchurch Clinical Studies Trust and
University of Otago, Christchurch, New Zealand; 15 Santa Maria
Annunziata Hospital, Florence, Italy; 16 Cedars-Sinai Medical Center,
Los Angeles, CA; 17 Henry Ford Health System, Detroit, MI;
18 Gilead Sciences, Inc., Foster City, CA; 19 Beth Israel Deaconess
Medical Center, Boston, MA; 20 Queen Mary University of London,
London, United Kingdom
Introduction: GS-5816 is a pangenotypic HCV NS5A inhibitor.
In Phase 2 studies, the combination of sofosbuvir (SOF) and
GS-5816 for 12 weeks demonstrated high efficacy in patients
with genotype 3 HCV. This Phase 3 study compared treatment
with a fixed dose combination (FDC) of SOF/GS-5816 for
12 weeks to standard of care, SOF+RBV for 24 weeks, in
patients with genotype 3 HCV. Methods: Patients at 75 sites
in North America, Europe, Australia and New Zealand were
randomized 1:1 to received SOF/GS-5816 (400 mg /100
mg daily) FDC for 12 weeks or SOF (400mg daily) with RBV
(1000-1200mg daily) for 24 weeks. HCV RNA was measured
with the CAP/CTM HCV 2.0 assay with LLOQ =15 IU/mL The
primary endpoint was sustained virologic response 12 weeks
after treatment (SVR12) with a pre-specified non-inferiority margin
of 10%. Results: Of 552 patients randomized and treated,
62% were male, 89% were white, 39% had IL28B CC genotype,
26% had prior treatment failure, and 30% had cirrhosis.
Eight patients discontinued treatment due to adverse events,
all of which were in the SOF +RBV treatment group. The most
common AEs (>10% in either treatment group) are presented
below. Five patients in the SOF/GS-5816 treatment group
and 8 patients in the SOF+RBV treatment group experienced
SAEs. One SAE, acute generalized exanthematous pustulosis,
in a SOF+RBV treated patient was assessed as related to study
drugs by the investigator. Hemoglobin decline and total bilirubin
increases were more commonly observed in the group
treated with SOF +RBV consistent with RBV–induced hemolysis.
No other significant lab abnormalities were observed. HCV
RNA declined rapidly in both treatment groups with 92% and
88% of patients achieving HCV RNA < LLOQ after 4 weeks
of treatment in the SOF/GS-5816 and SOF+RBV treatment
groups, respectively. SVR12 data for all patients will be presented.
Conclusions: The once daily, all-oral, single tablet regimen
of SOF/GS-5816 was well tolerated in treatment-naïve
and treatment-experienced genotype 3 HCV-infected patients