subjects with genotype 2 or 3 CHC irrespective of prior treatment history or ability to take interferon. Subjects in these trials had compensated liver disease including cirrhosis. SOVALDI was administered at a dose of 400 mg once daily. The ribavirin (RBV) dose was weight-based at 1000-1200 mg daily administered in two divided doses when used in combination with SOVALDI, and the peginterferon alfa 2a dose, where applicable, was 180 micrograms per week. Treatment duration was fixed in each trial and was not guided by subjects’ HCV RNA levels (no response guided algorithm). Plasma HCV RNA values were measured during the clinical trials using the COBAS TaqMan HCV test (version 2.0), for use with the High Pure System. The assay had a lower limit of quantification (LLOQ) of 25 IU per mL. Sustained virologic response (SVR) was the primary endpoint which was defined as HCV RNA less than LLOQ at 12 weeks after the end of treatment.
14.2 Clinical Trials in Subjects with Genotype 1 or 4 CHC
Treatment-Naïve Adults ─ NEUTRINO (Study 110)
NEUTRINO was an open-label, single-arm trial that eva luated 12 weeks of treatment with SOVALDI in combination with peginterferon alfa 2a and ribavirin in treatment-naïve subjects with genotype 1, 4, 5 or 6 HCV infection compared to pre-specified historical control.
Treated subjects (N=327) had a median age of 54 years (range: 19 to 70); 64% of the subjects were male; 79% were White, 17% were Black; 14% were Hispanic or Latino; mean body mass index was 29 kg/m2 (range: 18 to 56 kg/m2); 78% had baseline HCV RNA greater than 6 log10 IU per mL; 17% had cirrhosis; 89% had HCV genotype 1; 9% had HCV genotype 4 and 2% had HCV genotype 5 or 6. Table 8 presents the response rates for the treatment group of SOVALDI + peginterferon alfa + ribavirin.
Table 8 Response Rates in Study NEUTRINO
SOVALDI + Peg-IFN alfa + RBV 12 weeks
N=327a
Overall SVR
90% (295/327)
Genotype 1b
89% (261/292)
Genotype 1a
92% (206/225)
Genotype 1b
82% (54/66)
Genotype 4
96% (27/28)
Outcome for subjects without SVR
On-treatment virologic failure
0/327
Relapsec
9% (28/326)
Otherd
1% (4/327)
a. Including seven subjects with genotype 5 or 6 infection.
b. One subject had genotype 1a/1b mixed infection.
c. The denominator for relapse is the number of subjects with HCV RNA <LLOQ at their last on-treatment assessment.
d. Other includes subjects who did not achieve SVR and did not meet virologic failure criteria (e.g., lost to follow-up).
Response rates for selected subgroups are presented in Table 9.
Table 9 SVR Rates for Selected Subgroups in NEUTRINO
SOVALDI + Peg-IFN alfa + RBV 12 weeks
Cirrhosis
No
92% (252/273)
Yes
80% (43/54)
Race
Black
87% (47/54)
Non-black
