studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 313A
Marc Bilodeau - Advisory Committees or Review Panels: Verlyx, Bayer, Astellas;
Consulting: GSK; Grant/Research Support: Merck, Synageva; Speaking and
Teaching: Merck, Vertex, Abbvie, Aptalis, Roche
Eric M. Yoshida - Advisory Committees or Review Panels: Hoffman LaRoche, Gilead
Sciences Inc, Abbvie; Grant/Research Support: Abbvie, Hoffman LaRoche,
Merck Inc, Vertex Inc, Jannsen Inc, Gilead Sciences Inc, Boeringher Ingleheim
Inc, Astellas; Speaking and Teaching: Gilead Sciences Inc, Merck Inc
Curtis Cooper - Advisory Committees or Review Panels: Gilead, Abbvie, MERCK;
Grant/Research Support: MERCK, Gilead, Abbvie; Speaking and Teaching:
MERCK, Abbvie, Gilead
The following authors have nothing to disclose: Nabiha Faisal, Bandar Aljudaibi,
Geri Hirsch, Tarana Hussaini, Peter Ghali, Stephen E. Congly, Mang M. Ma,
Jennifer Leonard, Kevork M. Peltekian, Nazia Selzner, Les Lilly
205
A Randomized Controlled Trial of Sofosbuvir/GS-5816
Fixed Dose Combination for 12 Weeks Compared to
Sofosbuvir with Ribavirin for 12 Weeks in Genotype 2
HCV Infected Patients: The Phase 3 ASTRAL-2 Study
Mark S. Sulkowski 1 , Norbert Brau 2 , Eric Lawitz 3 , Mitchell L. Shiffman
4 , William J. Towner 5 , Peter J. Ruane 6 , Brian Doehle 7 , Jing
Wang 7 , John McNally 7 , Anu Osinusi 7 , Diana M. Brainard 7 , John
G. McHutchison 7 , Nancy Reau 8 , Keyur Patel 9 ; 1 Johns Hopkins University,
Baltimore, MD; 2 James J. Peters VA Medical Center, Bronx,
NY and Icahn School of Medicine at Mount Sinai, New York, NY;
3 Texas Liver Institute, University Of Texas Health Science Center,
San Antonio, TX; 4 Liver Institute of Virginia, Richmond, VA; 5 Kaiser
Permanente, Los Angeles, CA; 6 Ruane Medical, Los Angeles, CA;
7 Gilead Sciences, Inc., Foster City, CA; 8 University of Chicago
Medical Center, Chicago, IL; 9 Duke University School of Medicine,
Durham, NC
Introduction: GS-5816 is a pangenotypic HCV NS5A inhibitor
that has demonstrated high efficacy in genotype 1-6 HCV-infected
patients when administered for 12 weeks in combination
with sofosbuvir. The Phase 3 ASTRAL-2 study compared the
efficacy and safety of treatment with a fixed dose combination
(FDC) of SOF/GS-5816 for 12 weeks to SOF + RBV for 12
weeks in treatment-naïve and treatment-experienced genotype
2 HCV-infected patients, with and without cirrhosis. Methods:
Enrolled patients were randomized 1:1 to receive either SOF/
GS-5816 (400 mg /100 mg daily) FDC for 12 weeks or SOF
(400mg daily) with RBV (1000-1200mg daily) for 12 weeks.
Randomization was stratified by prior treatment and cirrhosis
status. 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%. All patients
have completed treatment and are in follow-up. Results: 266
patients with genotype 2 HCV infection were randomized and
treated, 134 with SOF/GS-5816 and 132 with SOF+RBV.
Overall 59% were male, 88% were white, 38% had IL28B
CC genotype, 15% had prior treatment failure, and 14% had
compensated cirrhosis. HCV RNA declined rapidly in both
treatment groups with > 90% of patients having HCV RNA
< LLOQ at treatment week 4. The SVR4 rate for the SOF/
GS-5816 treated patients is 99% (133/134) and for the
SOF+RBV treated patients is 96% (127/132). There were no
patients with relapse in the SOF/GS-5816 group compared
with 4 patients with relapse in the SOF+RBV treated group
through posttreatment week 4. Complete SVR12 and resistance
results will be presented. Two patients discontinued treatment,
one treated with SOF/GS-5816 discontinued on Day 1 for
adverse events (anxiety, headache and disturbance in attention)
and one treated with SOF+RBV did not return for study
visits after week 10. The most common AEs were fatigue,
headache, nausea, and insomnia and all were more frequently
observed in the SOF+RBV treated patients. Two patients in
each treatment group experienced SAEs, none were considered
related to study drugs. Hemoglobin declined to < 10g/dL
in 6 (5%) patients taking SOF+RBV but not in patients taking
SOF/GS-5816. No other significant laboratory abnormalities
were observed. Conclusions: Treatment with SOF/GS-5816
FDC for 12 weeks resulted in high SVR4 rates and was well tolerated
in treatment-naïve and treatment-experienced genotype
2 HCV-infected patients with and without cirrhosis. Few (