SOF + PEG-IFNa-2a + RBV
Open-labelSingle arm
≥ 18 yearsChronic HCV infectionGenotype 1, 4, 5 or 6
Treatment-naïveHCV RNA ≥ 10,000
IU/mlCompensated cirrhosis
allowed
W12
SVR12
W24
N = 327
NEUTRINO Lawitz E. NEJM 2013;368:1878-87
NEUTRINO Study: SOF + PEG-IFNa-2a + RBV
Design
– SOF : 400 mg qd– PEG-IFNa-2a : 180 mg SC once weekly– RBV (bid dosing) : 1000 mg/day if < 75 kg or 1200
mg/day if ≥ 75 kg Objective– SVR12 > 60%, 90% power
NEUTRINO Study: SOF + PEG-IFNa-2a + RBV
SOF + PEF-IFNa-2a + RBV
Mean age, years 52
Female 36%
Race : white/black 79% / 17%
HCV genotype1a1b456
225 (69%)66 (20%)28 (9%)1 (< 1%)6 (2%)
IL28B CC genotype 29%
HCV RNA log10 IU/ml, mean (SD) 6.4 ± 0.7
Cirrhosis 17%
Discontinued treatment, N 7 (5 due to AE)
Returned for post-treatment W4 visit 324
Returned for post-treatment W12 visit 301
NEUTRINO Lawitz E. NEJM 2013;368:1878-87
Baseline characteristics and patient disposition
HCV RNA < 25 IU/ml
25
50
100
75
99%
99.7
During treatment
W4
92 90
N = 325 327 327 327
W12
Post-treatment (SVR)
W4 W12
Genotype Cirrhosis
SVR12 by genotype, cirrhosis and IL28B
IL28B
SVR12 = 90% (95% CI : 87 -93) : superiority to adjusted historal SVR12 of 60% (two-sided exact test, p < 0.001)
NEUTRINO Lawitz E. NEJM 2013;368:1878-87
NEUTRINO Study: SOF + PEG-IFNa-2a + RBV
92
1a
225
82
1b
66
96
4
28
98
CC
95
No
92
273
Non-CC
87
232
Yes
80
54
100
5-6
70
OR (95% CI) p
Cirrhosis (no vs yes) 3.92 (1.66 – 9.27) 0.0018
IL28B (CC vs non-CC) 7.99 (1.82 – 35.17) 0.006
RBV exposure, mg/kg/day 1.38 (1.15 – 1.66) 0.0005
NEUTRINO Lawitz E. NEJM 2013;368:1878-87
NEUTRINO Study: SOF + PEG-IFNa-2a + RBV
Virologic breakthrough during treatment : none Relapse in patients with HCV RNA < 25 IU/ml at end of
completed treatment : 28– 25/320 (8%) in patients who completed treatment– 3/6 (50%) in patients who did not complete treatment
Multivariate analysis of factors associated with SVR12
Resistance testing (sequencing) – 28 relapse
• No SOF-associated mutation (S282T)• 2 NS5B substitutions in > 2 subjects (no change in susceptibility to SOF)
NEUTRINO Study: SOF + PEG-IFNa-2a + RBV
SOF + PEF-IFNa-2a + RBV, N = 327
AE leading to treatment discontinuation 5 (2%)
Serious adverse event 4 (1%)
Most frequent adverse event
Fatigue 59%
Headache 36%
Nausea 34%
Insomnia 25%
Decreased appetite 18%
Influenza-like illness 16%
Chills 17%
Pyrexia 18%
Rash 18%
Diarrhea 12%
Pruritus 17%
Myalgia 14%
Irritability 13%
NEUTRINO Lawitz E. NEJM 2013;368:1878-87
Adverse events, n (%)
NEUTRINO Study: SOF + PEG-IFNa-2a + RBV
Summary– In this open-label, single-group study of SOF + PEG-IFN and
RBV in previously untreated patients with HCV genotype 1 or 4 infection, a SVR of 90% at 12 weeks was obtained
• In patients with genotype 1 infection who had cirrhosis SVR12 was lower than for patients without cirrhosis (81% vs 92%)
– Patients with genotype 1, 4, 5, or 6 infection who received 12 weeks of SOF + PEG-IFN + RBV had a very low rate of treatment discontinuation (2%)
– No virologic resistance was detected in patients who did not have a sustained virologic response
NEUTRINO Lawitz E. NEJM 2013;368:1878-87