Presentation is loading. Please wait.

Presentation is loading. Please wait.

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.

Published byBaldric Osborne Modified over 6 years ago

Similar presentations

Presentation on theme: "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."— Presentation transcript:

1 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 Open-label Design W8 W12 W16 GT1 (N = 88) GT2 (N = 32) GT3 (N = 53) ≥ 18 years Chronic HCV infection Genotype 1, 2 or 3 Treatment-naïve (GT1 or GT2) Treatment-naïve or PEG-IFN failure (GT3) HCV RNA ≥ IU/mL Compensated cirrhosis allowed * No HBV co-infection MK3 GT2 (N = 31) GT3 (N = 50) MK3 + RBV GT1 (N = 88) GT2 (N = 46) GT3 (N = 79) MK3 GT2 (N = 16) GT3 (N = 80) MK3 + RBV * Liver biopsy or Fibroscan > 12.5 kPa or Fibrotest  > APRI > 2 GT2 (N = 26) GT3 (N = 50) MK3 MK3 + RBV GT3 (N = 50) Uprifosbuvir 225 mg/GZR 50 mg/ruzasvir 30 mg FDC (MK3) = 2 tablets QD Objective Primary endpoint: SVR12 (HCV RNA < 15 IU/mL), full analysis set (patients having received ≥ 1 dose of study drug) C-CREST – Part B Lawitz E. AASLD 2016, Abs. 110 1

2 Baseline characteristics
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 Baseline characteristics Genotype 1 N = 176 Genotype 2 N = 151 Genotype 3 N = 337 Median age, years 55 57 52 Female, % 39 43 41 Race, white, % 89 90 HCV genotype 1a / 1b, % 51 / 49 - Metavir F4, % 38 35 HCV RNA log10 IU/mL, median 6.2 6.4 6.3 Treatment-naïve, % PEG-IFN experienced, % 100 56 44 HIV co-infection, % 6 3 4 C-CREST – Part B Lawitz E. AASLD 2016, Abs. 110 2

3 SVR12 (Full Analysis Set)
C-CREST study, Part B: uprifosbuvir (MK-3682)/GZR/ruzasvir (MK-8408) fixed-dose combination + RBV for genotypes 1, 2 and 3 - Phase II SVR12 (Full Analysis Set) 8 weeks 12 weeks 16 weeks % 98 98 100 97 100 97 96 100 93 95 86 80 60 40 20 n 42 48 46 40 63 62 26 103 159 75 Genotype 1a Genotype 1b Genotype 2 Genotype 3 Relapse 2 1 7 4 3 Discontinuation (DR-AE)* Reinfection* Non-virologic failure* *Genotype 1a 8W, No RBV: 1 patient achieved SVR8 but was reinfected with a different HCV strain at FW12 Genotype 1a 12W, No RBV: 1 patient died due to study-drug unrelated bacterial sepsis Genotype 2 8W + RBV: 1 patient discontinued at D5 due to drug-related AEs of fatigue, malaise; 1 patient lost to FU Genotype 2 12W, No RBV: 2 patients lost to follow-up Genotype 3 8W + RBV: 1 patient lost to follow-up Genotype 3 12W, No RBV: 1 patient withdrew due to pregnancy, lost to follow-up Genotype 3 16W: 1 patient lost to follow-up C-CREST – Part B Lawitz E. AASLD 2016, Abs. 110

4 SVR12 (per protocol), genotype 1 patients with or without cirrhosis
C-CREST study, Part B: uprifosbuvir (MK-3682)/GZR/ruzasvir (MK-8408) fixed-dose combination + RBV for genotypes 1, 2 and 3 - Phase II SVR12 (per protocol), genotype 1 patients with or without cirrhosis No cirrhosis Cirrhosis 8 Weeks 12 Weeks % 100 100 100 100 100 97 96 100 92 80 60 40 20 n 29 13 23 23 30 17 18 22 Genotype 1a Genotype 1b Genotype 1a Genotype 1b Relapse 1 C-CREST – Part B Lawitz E. AASLD 2016, Abs. 110

5 SVR12 (per protocol), genotype 2 or 3 or patients ± RBV
C-CREST study, Part B: uprifosbuvir (MK-3682)/GZR/ruzasvir (MK-8408) fixed-dose combination + RBV for genotypes 1, 2 and 3 - Phase II SVR12 (per protocol), genotype 2 or 3 or patients ± RBV Without RBV With RBV Genotype 2 Genotype 3 % 100 100 99 98 97 98 94 96 100 91 83 80 60 40 20 n 32 30 44 16 53 49 78 80 49 25 8 Weeks 12 Weeks 8 Weeks 12 Weeks 16 Weeks Relapse 3 4 1 2 Discontinuation (DR-AE) C-CREST – Part B Lawitz E. AASLD 2016, Abs. 110

6 C-CREST study, Part B: uprifosbuvir (MK-3682)/GZR/ruzasvir (MK-8408) fixed-dose combination + RBV for genotypes 1, 2 and 3 - Phase II SVR12 (per protocol), genotype 2 or 3 patients with or without cirrhosis No cirrhosis Cirrhosis Genotype 2 Genotype 3 % 100 100 98 98 100 100 96 94 100 80 60 40 20 n 30 14 50 28 50 30 16 33 12W, No RBV 12W, No RBV 12W + RBV 16W, No RBV Relapse 1 C-CREST – Part B Lawitz E. AASLD 2016, Abs. 110

7 C-CREST study, Part B: uprifosbuvir (MK-3682)/GZR/ruzasvir (MK-8408) fixed-dose combination + RBV for genotypes 1, 2 and 3 - Phase II SVR12 (per protocol), genotype 3 treatment-experienced patients with cirrhosis 12 Weeks 16 Weeks % 100 100 100 96 100 80 60 40 20 n 15 14 20 25 No RBV + RBV No RBV + RBV Relapse 1 C-CREST – Part B Lawitz E. AASLD 2016, Abs. 110

8 SVR12 according to the presence of NS5A RAVs
C-CREST study, Part B: uprifosbuvir (MK-3682)/GZR/ruzasvir (MK-8408) fixed-dose combination + RBV for genotypes 1, 2 and 3 - Phase II SVR12 according to the presence of NS5A RAVs Genotype 1a Genotype 1b Genotype 2 Genotype 3 Duration of treatment 8W 12W No RAVs * 33/35 (94%) 41/41 (100%) 38/39 (97%) 24/24 (100%) RAVs * 3/3 (100%) 6/6 (100%) 16/16 (100%) No L31M 31/33 (94%) 23/23 (100%) L31M 20/25 (80%) 28/28 (100%) No Y93H 95/97 (98%) 147/148 (95%) Y93H 2/4 (50%) 5/7 (71%) * RAVs : 28, 30, 31, 93 C-CREST – Part B Lawitz E. AASLD 2016, Abs. 110

9 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 Adverse events MK3 without RBV MK3 with RBV Drug-related adverse event, % 36 67 Serious adverse event, % 2 Drug-related serious adverse event, N (%) 2 (1) * Death, N (%) 1 (0.2) ** Discontinuation due to adverse event, N (%) 3 (0.6) 6 (3) Adverse event in > 10% of patients, % Headache Fatigue Nausea 19 15 11.3 27 29 Laboratory abnormalities, % Hemoglobin < 10 g/dL Bilirubin > 5 x baseline Late AST/ALT > 5 x ULN Creatinine elevation, grade 1 /grade 2 0.4 0.2 1 0.6 / 0.2 3 0 / 0 * 1 genotype 3-infected patient had an exacerbation of chronic obstructive pulmonary disease related to RBV ; 1 genotype 2-infected patient had a worsening of depression related to RBV ** 1 genotype 1-infected patient died due to a study drug-unrelated bacterial sepsis C-CREST – Part B Lawitz E. AASLD 2016, Abs. 110 9

10 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 Summary MK3 (uprifosbuvir/grazoprevir/ruzasvir) for 8 or 12 weeks was highly effective in genotype 1 patients (SVR12 = 97%) MK3 for 12 or 16 weeks was highly effective in genotype 2 patients (SVR12 = 98%) The addition of RBV did not increase SVR12 MK3 for 8, 12 or 16 weeks was highly effective in genotype 3 treatment-naïve or treatment-experienced patients (SVR12 = 96%) Efficacy was maintained in genotype 3 treatment-experienced patients with cirrhosis (SVR12 = 99%) Treatment with MK3 was generally safe and well-tolerated C-CREST – Part B Lawitz E. AASLD 2016, Abs. 110 10

Download ppt "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."

Similar presentations

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

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

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.
SOF/VEL 400/100 mg qd N = 75 W24 SOF/VEL > 18 years Chronic HCV infection Genotype 1 to 6 Naïve or treatment-experienced No prior treatment with NS5A or.

SOF/VEL 400/100 mg qd N = 75 W24 SOF/VEL > 18 years Chronic HCV infection Genotype 1 to 6 Naïve or treatment-experienced No prior treatment with NS5A or.
> 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.

> 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.

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: 564-72 C-SALVAGE Study: grazoprevir + elbasvir + RBV in genotype 1 with failure to PI-based regimen –NS3 and NS5A RAVs.

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.

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.
Sulkowski M. Lancet 2015;385:1087-97 C-WORTHY  Design Randomisation* Open-label > 18 years HCV genotype 1, treatment naïve HCV RNA ≥ 10,000 IU/ml No cirrhosis.

Sulkowski M. Lancet 2015;385: C-WORTHY  Design Randomisation* Open-label > 18 years HCV genotype 1, treatment naïve HCV RNA ≥ 10,000 IU/ml No cirrhosis.
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.

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 18-70 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.

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.

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

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

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.

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.
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*

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*
 Objective –SVR 12 (HCV RNA < 25 IU/ml), by ITT OBV/PTV/r + SOF + RBV OBV/PTV/r + SOF Not randomised Open-label QUARTZ-II Study: OBV/PTV/r + SOF for HCV.

 Objective –SVR 12 (HCV RNA < 25 IU/ml), by ITT OBV/PTV/r + SOF + RBV OBV/PTV/r + SOF Not randomised Open-label QUARTZ-II Study: OBV/PTV/r + SOF for HCV.
No HBV or HIV co-infection

No HBV or HIV co-infection
No cirrhosis or compensated cirrhosis * No HBV or HIV coinfection

No cirrhosis or compensated cirrhosis * No HBV or HIV coinfection
Design Randomisation* 1 : 1 Open-label W8 W12

Design Randomisation* 1 : 1 Open-label W8 W12
ARV-trial.com RUBY-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir for HCV genotype 1a or 4 with severe renal impairment Design Open label W12.

ARV-trial.com RUBY-II Study: ombitasvir/paritaprevir/ritonavir + dasabuvir for HCV genotype 1a or 4 with severe renal impairment Design Open label W12.

Similar presentations

Ads by Google