C-SWIFT Study: grazoprevir/elbasvir + SOF in genotypes 1 or 3, with or without cirrhosis > 18 years...

C-SWIFT Study: grazoprevir/elbasvir + SOF in genotypes 1 or 3, with or without cirrhosis

> 18 yearsChronic HCV infection

Genotype 1 or 3Treatment-naïve

Cirrhosis assessed by liver biopsy or noninvasive testsNo HBV or HIV co-infection

GZR/EBR + SOF

GZR/EBR + SOF

GZR/EBR + SOF

GZR/EBR + SOF

GZR/EBR + SOF

GZR/EBR + SOF

GZR/EBR + SOF

W4 W6 W8 W12Randomisation

1 : 1Open-label

Cirrhosis

No randomisationOpen-label

Cirrhosis

No cirrhosis

No cirrhosis

N = 15

N = 31

N = 30

N = 20

N = 21

N = 12

N = 14

SVR12GZR/EBR 100/50 mg QD ; SOF 400 mg QD

Objective– SVR12 (HCV RNA < 15 IU/ml), with 95% CI, by ITT

Poordad F. EASL 2015, Abs. O006

Genotype 1

Genotype 3

Design

C-SWIFT

Genotype 1 Genotype 3

No cirrhosis Cirrhosis No cirrhosis Cirrhosis4 weeksN = 31

6 weeksN = 30

6 weeksN = 20

8 weeksN = 21

8 weeksN = 15

12 weeksN = 14

12 weeksN = 12

Mean age, years 52 51 56 57 51 42 55

Female 35% 37% 35% 38% 27% 43% 17%

Race, white 97% 93% 100% 100% 95% 100% 100%

IL28B CC 36% 27% 30% 24% 40% 21% 50%

Genotype1a1b

84%16%

87%13%

80%20%

76%24%

- - -

Cirrhosis, N (%) 0 0 20 (100) 21 (100) 0 0 12 (100)

HCV RNA x 106 IU/ml, mean

3.69 3.09 1.66 2.37 3.29 2.57 2.26


Poordad F. EASL 2015, Abs. O006C-SWIFT

Baseline characteristics


SVR12 (HCV RNA < 15 IU/ml), mITT, Genotype 1


33

8780

94

4 weeks0

201

6 weeks040

6 weeks040

8 weeks013

BreakthroughRelapseNon virologic failure

30 30 20 200

20

40

60

80

100%

Non-cirrhotic Cirrhotic


SVR12 (HCV RNA < 15 IU/ml), mITT, Genotype 3 Non-cirrhotic Cirrhotic

93100

91

0

20

40

60

80

100

8 weeks010

12 weeks000

12 weeks011

BreakthroughRelapseEarly discontinuation

15 14 11

%



SVR12 (HCV RNA < 15 IU/ml), per-protocol, Genotype 3, by subgroups

95 100

85

9791 93 100 93 96

0

20

40

60

80

100

All patients < 2 MIU/ml

> 2 MIU/ml

No cirrhosis Cirrhosis Male Female CC Non-CC

40 27 13 29 11 28 12 14 26

Baseline HCV RNA Gender IL28B genotype

%


NS3 RAV NS5A RAV NS5B RAV

Genotype 1 (29 relapses) 56

No resistance-associated variants 28/29 (97%) 18/30 (60%) 30/30

(100%)

Pre-existing baseline RAVs only 0 1 (3%) 0

RAVS detected at failure 1 (3%) 9 (30%)4/9 in 4W arm 0

RAVs at failure in addition of baseline RAVs 0 2 (7%) 0

Genotype 3 (2 relapses)

At baseline Q168Q/R 0 0

At relapse Q168R Y93H 0


Resistance analysis at failure



All patients

Genotype 1 Genotype 3

Non cirrhotic4 & 6 weeks

N = 61

Cirrhotic6 & 8 weeks

N = 41

Non cirrhotic8 & 12 weeks

N = 29

Cirrhotic12 weeks

N = 12

Discontinuation due to AE 1 (1) 0 1 (2) 0 0

Serious adverse event 2 (2) 0 2 (5) 0 0

Death 0 0 0 0 0

Most common AEs

Headache

Fatigue

Nausea

4 (4)

2 (2)2 (2)

1 (2)

2 (3)2 (3)

2 (7)

0

1 (2)

1 (3)

0

1 (3)

1 (8)

1 (8)

1 (8)

Hemoglobin < 10 g/dl 0 0 0 0

Total bilirubin > 5 x baseline 0 0 0 0 0

ALT/AST > 5 x ULN 0 0 0 0 0

Adverse events, N (%)



Summary

– Grazoprevir/elbasvir + sofosbuvir was able to shorten treatment duration to 8 weeks or less among cirrhotic and non-cirrhotic HCV genotype 1 infected patients

– Genotype 3 patients achieved high SVR12 rates with 8-12 weeks of therapy, including patients with cirrhosis

– All virologic failures were due to relapse– Patients relapsed most commonly with either wild-type virus or

with RAVs already present at baseline– GZR/EBR + SOF was generally safe and well tolerated


C-SWIFT Study: grazoprevir/elbasvir + SOF in genotypes 1 or 3, with or without cirrhosis > 18 years...

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