sof + peg-ifn -2a + rbv open-label single arm ≥ 18 years chronic hcv infection genotype 1, 4, 5...

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


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


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)



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



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)


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%


Adverse events, n (%)


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


sof + peg-ifn -2a + rbv open-label single arm ≥ 18 years chronic hcv infection genotype 1, 4, 5...

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