1. ARV-trial.com
IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease
Design
Open label
≥ 18 years
Chronic HCV infection
Genotype 1 or 4
HCV RNA > IU/ml
Treatment-naïve or pre-treated
with PEG-IFN ± RBV
Cirrhosis (> 14.5 kPa on FibroScan)
Portal hypertension or liver decompensation
No hepatocellular carcinoma
Total bilirubin ≤ 3 x ULN, Platelet ≥ 30,000/mm3, Albumin ≤ 2.5 g/dl, INR ≤ 2.5, eGFR ≥ 30 ml/min
No HBV or HIV co-infection
W12
N = 19
CP A < 7 + PH
SMV + DCV + SOF
SVR12
N = 21
CP B 7-9
SMV + DCV + SOF
CP : Child-Pugh ; PH : portal hypertension
Post-treatment follow-up of 5 years
SMV 150 mg qd + DCV 90 mg qd + SOF 400 mg qd
Objective
SVR12 (HCV RNA < 15 IU/ml), with 2-sided 95% CI, by ITT
IMPACT
Lawitz E. J Viral Hepat 2017; 24:287-94 1

2. Baseline characteristics
ARV-trial.com
IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease
Baseline characteristics
CP A, N = 19
CP B, N = 21
Median age, years 56 61
Female, % 26 48
Race : white / black, %
95 / 5
100 / 0
Body mass index, median
26.8
31.8
Genotype, n
1a (NS3 Q80K) 1b 4
15 (9/15) 3 1
11 (3/10) 10
IL28B CC genotype, % 21 14
HCV RNA log10 IU/ml, median
5.78
5.60
Treatment-experienced, % 47
Fibroscan score, kPa, median
21.8
30.8
Child-Pugh score : 5 / 6 / 7 / 8 / 9, n
14 / 5 / 0 / 0 / 0
0 / 0 / 9 / 8 / 4
MELD score < 10 / / ≥ 15, n
12 / 7 / 0
10 / 9 / 2
Albumin, g/dl, median
4.1
3.2
Platelets x 103/mm3, median
106 79
IMPACT
Lawitz E. J Viral Hepat 2017; 24:287-94 2

3. ARV-trial.com
IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease
Outcome
CP A, N = 19
CP B, N = 21
SVR12 (HCV RNA < 15 UI/ml)
100%
Change in Child-Pugh score at follow-up W12
Change in MELD score at follow-up W12
Baseline CP score -2 6 8 -6 -4 2 4
Baseline MELD score -3 -2 2 3 -1 1
5–6
7–9
< 10
≥ 10-< 15
≥ 15
Decreased, N = 11
No change, N = 23
Increased, N = 6
Decreased, N = 20
No change, N = 13
Increased, N = 7
IMPACT
Lawitz E. J Viral Hepat 2017; 24:287-94 3

4. IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease
SMV, DCV and SOF pharmacokinetics
following administration of SMV + DCV + SOF
Intensive PK analysis performed at Week 2 and Week 8
Mean SMV exposure: 2.2-fold higher in CP B than CP A
Mean DCV exposure: similar in CP B and CP A (1.2-fold higher in CP B)
Mean SOF exposure: 1.5-fold higher in CP B than CP A
Mean GS exposure (SOF metabolite): similar in CP B and CP A
IMPACT
Lawitz E. J Viral Hepat 2017; 24:287-94

5. IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease
Adverse events and laboratory abnormalities, N (%)
CP A, N = 19
CP B, N = 21
Serious adverse event
1 (5)
GI haemorrhage, not related
Adverse event related to study drug
3 (16)
7 (33)
Adverse event leading to discontinuation
Death
Adverse event in ≥ 2 patients in any group, N
Pruritus
Urinary tract infection
Photosensitivity
Nausea
Hepatic encephalopathy
Anemia
Insomnia
Irritability 1 2
1 0
Total bilirubin grade 3 / grade 4, N
2 / 0
5 / 2
Lipase grade 3 / grade 4, N
0 / 1
1 / 0
Glucose elevations grade 3 / grade 4, N
1 / 1
IMPACT
Lawitz E. J Viral Hepat 2017; 24:287-94

6. IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease
Summary
Treatment for 12 weeks with SMV, SOF, and DCV resulted in 100% response rate; all 19 Child-Pugh A patients and all 21 Child-Pugh B patients achieved SVR12
High virologic response was observed regardless
of Child-Pugh class (<7 or 7–9)
or the presence of resistance-associated variants at baseline
This 3-DAA combination was generally safe and well tolerated
No discontinuations due to adverse events
No deaths
5-year follow-up will be important in providing long-term outcomes in association with SVR
IMPACT
Lawitz E. J Viral Hepat 2017; 24:287-94