LDV/SOF Failure Open-label W24 Chronic HCV infection Genotype 1 Failure to achieve SVR on LDV/SOF-containing regimen Compensated cirrhosis (liver biopsy.

Slides:

Advertisements

Similar presentations

ATOMIC  Design  Objective –SVR 24 by ITT-analysis, detection of a 30% or 25% difference between two treatment groups, 2-sided significance level of 5%,

Advertisements

ALLY-1  Design  Objective –SVR 12 (HCV RNA < 25 IU/ml) in genotype 1 DCV 60 mg qd + SOF 400 mg qd + RBV DCV 60 mg qd + SOF 400 mg qd + RBV Not randomised.

Roth D. EASL 2015, Abs. LP02 C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease N = 111 GZR + EBR Placebo GZR + EBR (Intensive.

LDV/SOF 90/400 mg qd Non-randomised Open-label N = 21 W12 SVR 12 NIAID SYNERGY GT4 Kohli A. Lancet Infect Dis 2015; Juky 15, ePub ahead of print ≥ 18 years.

OBV/PTV/r + DSV + RBV Placebo Randomisation** 3 : 1 Double blind years Chronic HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Failure to pre-treatment with.

CURRY  Design Open-label CURRY Study: SOF + RBV for HCV with liver cancer before transplantation ≥ 18 years Chronic HCV infection Any genotype HCV RNA.

Egyptian Ancestry  Design  Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI SOF 400 mg qd + RBV Randomised 1 : 1 Open-label Egyptian Ancestry Study:

OBV/PTV/r Open label years Chronic HCV infection Genotype 1b Treatment-naïve or failure to PEG-IFN + RBV HCV RNA > 10,000 IU/ml Without or with cirrhosis*

AI Study  Design SOF 1W then DCV + SOF 23W DVC + SOF Randomisation* 1 : 1 : 1 Open-label AI Study: DCV + SOF + RBV for genotypes 1, 2 and.

No HBV or HIV co-infection

SOF + PEG-IFN  -2a + RBV Open-label Single arm ≥ 18 years Chronic HCV infection Genotype 1, 4, 5 or 6 Treatment-naïve HCV RNA ≥ 10,000 IU/ml Compensated.

SMV SOF 400 Open-label OPTIMIST-2 Study: SMV + SOF for genotype 1 and cirrhosis W12  Objective –Superiority of SVR 12 (HCV RNA historical control.

SMV 150 mg QD + SOF 400 mg QD Randomisation 1 : years HCV genotype 1 Naïve or pre-treated with IFN-based regimen No cirrhosis HCV RNA ≥

UNITY-1 DCV/ASV/BCB No randomisation Open-label UNITY-1 Study: daclatasvir/asunaprevir/beclabuvir in genotype 1 without cirrhosis  Design W12 ≥ 18 years.

NIAID ERADICATE Open-label W12 ≥ 18 years Chronic HCV infection Genotype 1 Treatment naïve HIV infection on stable ART ≥ 8 weeks and HIV RNA < 50 c/ml.

Placebo + PR W48 Placebo + PR Yes Hezode C. Gut 2015;64: COMMAND-1 COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4 DCV60 + PEG-IFN.

SIRIUS Placebo LDV/SOF + placebo Randomisation* 1 : 1 Double-blind SIRIUS Study: LDV/SOF ± RBV for genotype 1 and cirrhosis with non response to prior.

ION-4  Design LDV/SOF Open-label ION-4 Study: LDV/SOF in HIV co-infection W12 ≥ 18 years Chronic HCV infection Genotype 1 or 4 HCV RNA ≥ 10,000 IU/ml.

ARV-trial.com C-SWIFT Study: grazoprevir/elbasvir + SOF in genotypes 1 or 3, with or without cirrhosis Randomisation 1 : 1 Open-label Design W4 W6 W8.

ION-1  Design LDV/SOF LDV/SOF + RBV Randomisation* 1 : 1 : 1 : 1 Open-label ION-1 Study: LDV/SOF + RBV for genotype 1 W24W12 ≥ 18 years Chronic HCV infection.

OBV/PTV/r Placebo Randomisation** 2 : years Chronic HCV Genotype 1b HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated, no prior failure with DAA Without.

SOLAR-1 LDV/SOF + RBV Randomisation* of the 7 groups 1 : 1 Open-label SOLAR-1 Study: LDV/SOF + RBV in advanced liver disease  Design W12W24 ≥ 18 years.

ALLY-3  Design  Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI DCV 60 mg qd + SOF 400 mg qd Not randomised Open-label ALLY-3 Study: DCV + SOF for.

> 18 years Chronic HCV infection Genotype 1 Failure (relapse) to 4, 6 or 8 weeks of GZR/EBR + SOF in C-SWIFT Part A Compensated cirrhosis assessed by liver.

SOF/VEL 400/100 mg qd N = 500 N = 100 W12 Placebo > 18 years Chronic HCV infection Genotype 1, 2, 4, 5 or 6 Naïve or pre-treatment with IFN-based regimen.

Forns X. J Hepatology 2015; 63: C-SALVAGE Study: grazoprevir + elbasvir + RBV in genotype 1 with failure to PI-based regimen –NS3 and NS5A RAVs.

SOF/VEL 400/100 mg qd N = 250 W24 SOF + RBV W12 * Randomisation was stratified on prior treatment (naïve or experienced) and cirrhosis (yes or no) ** Metavir.

OBV/PTV/r + DSV Open label Chronic HCV infection Genotype 1 Treatment-naïve HCV RNA > 1,000 IU/ml Chronic kidney disease with eGFR < 30 ml/min/1.73m 2.

No randomisation Open-label years HCV genotype 1 Naïve or null-response to PEG-IFN + RBV HCV RNA > 10,000 IU/ml No cirrhosis No HBV or HIV co-infection.

 Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI, next observation carried backward DCV + SOF + RBV Randomised* 1:1 Open-label ALLY-3+ study: DCV.

SOF + RBV Randomisation* 1 : 1 : 1 Open-label BOSON Study: SOF + RBV + PEG-IFN for genotypes 2 and 3 ≥ 18 years Chronic HCV infection Genotype 2, treatment-

Open-label W24 ≥ 18 years Chronic HCV infection All genotypes HCV RNA ≥ 10,000 IU/ml Liver transplantation months earlier Child Pugh ≤ 7 and MELD.

SOF/VEL 400/100 mg qd N = 120 W12 SOF + RBV > 18 years Chronic HCV infection Genotype 2 Naïve or pre-treatment with IFN-based regimen Compensated cirrhosis.

C-EDGE TN Study: grazoprevir/elbasvir in genotype 1, 4 or 6 Zeuzem S. Ann Intern Med 2015; 163:1-13 GZR/EBR 100/50 mg qd N = 316 N = 105  Design W12W24.

Poordad F. NEJM 2014;368: D Phase IIa  Design  Treatment regimens – Paritaprevir/rironavir (PTV/r) : PTV 250 or 150 mg qd/ritonavir 100 mg qd (2.

LDV/SOF Open-label Chronic HCV infection Genotype 1 Failure to achieve SVR 12 on a short-course of 1 st line LDV/SOF-containing regimen No cirrhosis N.

SOF/VEL 400/100 mg qd N = 106 W12 > 18 years Chronic HCV infection Genotype 1-6 Naïve or pre-treatment with IFN-based regimen Compensated cirrhosis allowed*

No HBV or HIV co-infection

LDV/SOF Randomisation * 1:1 Open-label ≥ 20 years, Japanese Chronic HCV infection Genotype 1 HCV RNA ≥ IU/ml Treatment-naive, or pre-treated Compensated.

No cirrhosis or compensated cirrhosis * No HBV or HIV coinfection

Design Randomisation* 1 : 1 Open-label W8 W12

Design Randomisation * 1 : 1 Open-label W16 W24 > 18 years

No HBV or HIV co-infection

ARV-trial.com SURVEYOR-II study – Part 3: glecaprevir/pibrentasvir + RBV in genotype 3 with treatment experience and/or cirrhosis Design Randomisation.

C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis

Design No randomisation Open-label W12 W years HCV genotype 1

PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection

> 18 years Chronic HCV infection Compensated cirrhosis **

ARV-trial.com C-CREST study, Part B: uprifosbuvir (MK-3682)/GZR/ruzasvir (MK-8408) fixed-dose combination + RBV for genotypes 1, 2 and 3 - Phase II Randomisation.

Compensated cirrhosis No HBV or HIV co-infection

No HBV or HIV co-infection

Retreatment study: SOF/VEL + RBV in prior NS5A failure - Phase II

Creatinine clearance ≥ 50 ml/min No HBV or HIV co-infection

Design Randomisation* 1 : 1 Open-label W12

Failure to achieve SVR on No HBV or HIV co-infection

QUARTZ II-III : OBV/PTV/r + SOF RBV in genotype 2 or 3

Design Randomisation* 1 : 1 Double blind W12

SOF/VEL + GS-9857 in genotypes 1-6 Phase II

LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1

ARV-trial.com SURVEYOR-II study – Part 3: glecaprevir/pibrentasvir ± RBV in genotype 3 with treatment experience and/or cirrhosis Design Randomisation.

Design W12 Randomisation * Open-label

GS-US Study: SOF/VEL + GS-9857 in genotype 1 - Phase II

ION-3 Study: LDV/SOF + RBV for naïve genotype 1

GS-US Study: SOF/VEL + GS in genotype 2, 3, 4 or 6 - Phase II

MAGELLAN-3 Study: GLE/PIB + SOF + RBV in patients who failed GLE/PIB

LDV/SOF ± RBV in genotype 3 or 6 – Phase 2

Study : LDV/SOF in genotype 5

ARV-trial.com C-CREST study, Part B: uprifosbuvir (MK-3682)/GZR/ruzasvir (MK-8408) fixed-dose combination + RBV for genotypes 1, 2 and 3 - Phase II Randomisation.

SOF/VEL in liver transplantation with genotype 1-4 infection

SOF/VEL ± RBV in genotype 3 with compensated cirrhosis

Presentation transcript:

LDV/SOF Failure Open-label W24 Chronic HCV infection Genotype 1 Failure to achieve SVR on LDV/SOF-containing regimen Compensated cirrhosis (liver biopsy or Fibrotest > APRI > 2) allowed No HBV or HIV co-infection  Objective –Primary endpoint : SVR 12 (HCV RNA < 15 IU/ml) by intention to treat, with 2-sided 95% CI, no statistical hypothesis LDV/SOF 90/400 x 1 qd SVR 12 N = 41  Design LDV/SOF Failure Study: LDV/SOF for retreatment of genotype 1 with prior failure to LDV/SOF Lawitz E. EASL 2015, Abs. O005

LDV/SOF Failure Study: LDV/SOF for retreatment of genotype 1 with prior failure to LDV/SOF N = 41 Mean age, years58 Female17% IL28B CC genotype7% HCV RNA log 10 IU/ml, mean6.2 Cirrhosis46% Genotype 1a83% Prior HCV treatment LDV/SOF + RBV LDV/SOF + GS % 20% Prior HCV treatment duration 8 weeks Presence of NS5A RAVs 30 (73%) 19/30 (63%) Prior HCV treatment duration 12 weeks Presence of NS5A RAVs 11 (27%) 11/11 (100%) Lawitz E. EASL 2015, Abs. O005 LDV/SOF Failure Baseline characteristics

SVR 12 (HCV RNA < 15 IU/ml) % N AllNoYes Q30R or M28T L31MY93H/NNoYes≥ 28W Cirrhosis W Prior treatment duration Baseline NS5A RAVs 100 None 11 Number of NS5A RAVs Type of single NS5A RAVs LDV/SOF Failure Study: LDV/SOF for retreatment of genotype 1 with prior failure to LDV/SOF Lawitz E. EASL 2015, Abs. O005 LDV/SOF Failure 0

 NS5B Resistance analysis –Baseline : No NS5B resistance associated (S282T) or treatment- emergent (L159F, V321A) variants were detected –At virologic failure : NS5B variants detected in 4 of 12 (33%) patients S282T (N = 2) L159F (N = 1) Double-mutant S282T + L159F (N = 1)  Adverse events –Serious adverse events : 3 –Discontinuation due to adverse event : 0 –Grade 3 adverse events : 3 (none related to study drug) –Adverse events in ≥ 10% of patients : headache, fatigue –Grade 3 laboratory abnormality : 2 LDV/SOF Failure Study: LDV/SOF for retreatment of genotype 1 with prior failure to LDV/SOF Lawitz E. EASL 2015, Abs. O005 LDV/SOF Failure

LDV/SOF Failure Study: LDV/SOF for retreatment of genotype 1 with prior failure to LDV/SOF  Summary –71% of patients who failed prior LDV/SOF-containing regimens achieved SVR 12 when retreated with LDV/SOF for 24 weeks –The presence of baseline NS5A RAV(s), which was more likely to develop with longer prior LDV/SOF treatment, was associated with virologic failure –Emergence of S282T was observed in 3 of 12 virologic failures Lawitz E. EASL 2015, Abs. O005 LDV/SOF Failure