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Design Randomisation* 1 : 1 Double blind W12

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Presentation on theme: "Design Randomisation* 1 : 1 Double blind W12"— Presentation transcript:

1 POLARIS-1 study: SOF/VEL/VOX in NS5A inhibitor-experienced patients with genotype 1 to 6
Design Randomisation* 1 : 1 Double blind W12 > 18 years Chronic HCV infection Genotype 1, 2, 3, 4, 5 or 6 NS5A inhibitor-experienced for ≥ 4 weeks (exclusion if discontinued due to an adverse event or unsuccessful due to non-compliance) Compensated cirrhosis ** allowed N = 263 SOF/VEL/VOX 400/100/100 mg QD SVR12 Placebo N = 152 * Randomisation only in genotype 1, stratified on cirrhosis (yes or no) ; No randomisation (open-label SOF/VEL/VOX) for all other genotypes ** Metavir F4 or Ishak 5-6 or Fibroscan > 12.5 kPa or Fibrotest > APRI > 2 Objective SVR12 (HCV RNA < 15 IU/mL), with 95% CI, by ITT: superiority > 10% to a prespecified rate of 85% (2-sided significance level of 5%), for each regimen, 90% power POLARIS-1 Bourlière M. NEJM 2017; 376:

2 Baseline characteristics and patient disposition
POLARIS-1 study: SOF/VEL/VOX in NS5A inhibitor-experienced patients with genotype 1 to 6 Baseline characteristics and patient disposition SOF/VEL/VOX N = 263 Placebo N = 152 Age, years, mean 58 59 Female, % 24 20 White, % 80 82 Genotype, % 1a 1b 1 other 2 3 4 5 / 6 / unknown 38 17 2 30 8 < 1 / 2 / < 1 77 1 0 / 1 / 0 HCV RNA, log10 IU/mL, mean 6.3 Cirrhosis, % 46 34 Previous HCV treatment, % NS5A + NS3 +± NS5B NS5A + NS5B NS5A NS5B ± NS3 ≥ 2 regimens < 1 39 33 Discontinuation, N (adverse event / lost to follow-up) 2 (1 / 1) 3 (3 / 0) POLARIS-1 Bourlière M. NEJM 2017; 376:

3 SOF/VEL/VOX 12 weeks: SVR12 overall and by subgroups, % (95% CI)
POLARIS-1 study: SOF/VEL/VOX in NS5A inhibitor-experienced patients with genotype 1 to 6 SOF/VEL/VOX 12 weeks: SVR12 overall and by subgroups, % (95% CI) % 96.2 * (93-98) 99 (95-100) 100 (92-100) 96 (90-99) 100 (48-100) 100 (54-100) 93 (87-97) 95 (87-99) 91 (71-99) 100 97 100 80 6 relapses 1 on-treatment failure 2 withdrew consent 1 lost to follow-up 6 relapses 1 on-treatment failure 1 withdrew consent 60 40 1 withdrew consent 1 lost to follow-up 20 N= 263 142 121 150 101 45 5 78 22 1 6 Total No Yes 1 1a 1b 2 3 4 5 6 Cirrhosis Genotype * Superiority to 85% (p < 0.001) POLARIS-1 Bourlière M. NEJM 2017; 376:

4 SVR12 by baseline RASs (15% cutoff), %
POLARIS-1 study: SOF/VEL/VOX in NS5A inhibitor-experienced patients with genotype 1 to 6 SVR12 by baseline RASs (15% cutoff), % % 97.7 100 100 97.1 96.8 97.2 80 60 40 20 N= 43 205 9 124 72 No RASs Any RASs NS3 only NS5A only NS3 + NS5A Two patients had S282T at baseline, both achieved SVR12 None of the patients who relapsed had treatment-emergent RASs POLARIS-1 Bourlière M. NEJM 2017; 376:

5 Characteristics of patients with virologic failure (n = 7)
POLARIS-1 study: SOF/VEL/VOX in NS5A inhibitor-experienced patients with genotype 1 to 6 Characteristics of patients with virologic failure (n = 7) Sex, age, race Genotype Cirrhosis HCV RNA, log10 IU/mL Prior HCV regimen Resistance-associated substitutions NS3 NS5A Baseline Relapse M, 61, white 1a Yes 6.7 LDV/SOF 24W Q80K Y93N M, 60, white 3a 7.6 SOF/VEL 12W None Y93Y/H Y93H F, 62, White 6.3 DCV + SOF 12W A30K M, 65, white 4.9 DCV + SOF 25W 5.3 4d 5.7 LDV/SOF 12W L30R L30R + Y93H M, 60, black * LDV/SOF Q30T Q30T + L31L/M + Y93Y/H * Only patient with virologic breakthrough : low plasma concentrations of GS (the chief SOF metabolite), VEL, and VOX at weeks 8 and 12, suggestive of nonadherence POLARIS-1 Bourlière M. NEJM 2017; 376:

6 Angioedema attributed
POLARIS-1 study: SOF/VEL/VOX in NS5A inhibitor-experienced patients with genotype 1 to 6 Adverse events SOF/VEL/VOX N = 263 Placebo N = 152 At least one adverse event, % 78 70 Serious adverse events, N (%) related to study drug 5 (2%) 7 (5%) Grade 3-4 adverse events, N (%) 4 (3%) Discontinuation due to adverse event, N (%) 1 (< 1%) Angioedema attributed to ramipril 3 (2%) Death Adverse events in > 10% of patients, % Headache 25 17 Fatigue 21 20 Diarrhea 18 12 Nausea 14 8 Grade 3 / Grade 4 laboratory abnormalities, % 5 / 2 12 / 2 POLARIS-1 Bourlière M. NEJM 2017; 376:

7 POLARIS-1 study: SOF/VEL/VOX in NS5A inhibitor-experienced patients with genotype 1 to 6
Summary In NS5A-inhibitor experienced patients, treatment with SOF/VEL/VOX for 12 weeks resulted in a 96.2% SVR12 rate in difficult-to-cure patients with multiple unfavorable characteristics Treatment-emergent NS5A RAS was observed in 1/6 patients with relapse SOF/VEL/VOX was well tolerated with an adverse event profile similar to that observed in placebo recipients SOF/VEL/VOX for 12 weeks provides a single tablet, once daily, highly effective, RBV-free treatment for NS5A inhibitor-experienced patients POLARIS-1 Bourlière M. NEJM 2017; 376:

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