Presentation is loading. Please wait.

Presentation is loading. Please wait.

ARV-trial.com CORAL-I study cohorts 3 to 6: OBV/PTV/r + DSV + RBV in transplant recipients and genotype 1 or 4 Design W12 W24 No randomisation Open-label.

Published byMay Stafford Modified over 5 years ago

Similar presentations

Presentation on theme: "ARV-trial.com CORAL-I study cohorts 3 to 6: OBV/PTV/r + DSV + RBV in transplant recipients and genotype 1 or 4 Design W12 W24 No randomisation Open-label."— Presentation transcript:

1 ARV-trial.com CORAL-I study cohorts 3 to 6: OBV/PTV/r + DSV + RBV in transplant recipients and genotype 1 or 4 Design W12 W24 No randomisation Open-label ≥ 18 years HCV infection, genotype 1 or 4 Naïve or (PEG-) IFN ± RBV experienced HCV RNA > 1000 IU/mL Liver (LT) or renal transplant (RT) recipients Compensated cirrhosis or no cirrhosis Immunosuppressive regimen with tacrolimus or cyclosporine ; corticosteroids ≤ 10 mg/day permitted No HBV or HIV co-infection GT1a, N = 4 OBV/PTV/r + DSV + RBV Cohort 3 Genotype 1, LT, cirrhosis GT1b, N = 2 OBV/PTV/r + DSV + RBV GT1a, N = 22 Cohort 4 Genotype 1, LT, no cirrhosis OBV/PTV/r + DSV + RBV GT1b, N = 12 OBV/PTV/r + DSV GT1a, N = 9 OBV/PTV/r + DSV + RBV Cohort 5 Genotype 1, RT, no cirrhosis GT1b, N = 3 OBV/PTV/r + DSV No cirrhosis, N = 4 Cohort 6 Genotype 4, LT, OBV/PTV/r + RBV Cirrhosis, N = 1 OBV/PTV/r + RBV Treatment regimens Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r): 25/150/100 mg QD = 2 tablets Dasabuvir (DSV): 250 mg BID ; RBV: 1000 or mg/day divided twice daily Objective SVR12 (HCV RNA < 25 IU/mL), with 95% CI, by ITT, descriptive analysis CORAL-I , cohorts 3-6 Agarwal K, EASL 2017, Abs. FRI-267 1

2 Baseline characteristics
ARV-trial.com CORAL-I study cohorts 3 to 6: OBV/PTV/r + DSV + RBV in transplant recipients and genotype 1 or 4 Baseline characteristics Genotype 1 Genotype 4 Cohort 3 LT, cirrhosis N = 6 Cohort 4 LT, no cirrhosis N = 34 Cohort 5 RT, no cirrhosis N = 12 Cohort 6 LT N = 3 Female, % 33 12 25 White, % 100 97 58 Genotype 1a / 1b, % 67 / 33 62 / 35 75 / 25 - HCV RNA > IU/mL, % 83 85 IFN/PEG-IFN experienced, % 50 71 17 Cyclosporine / Tacrolimus, % 17 / 83 12 / 88 8 / 92 0 / 100 F0-F1/ F2 / ≥ F3, % 0 / 0 / 100 68 / 19 / 13 75 / 8 / 17 100 / 0 / 0 CORAL-I , cohorts 3-6 Agarwal K, EASL 2017, Abs. FRI-267 2

3 SVR12 by subgroup, ITT population
ARV-trial.com CORAL-I study cohorts 3 to 6: OBV/PTV/r + DSV + RBV in transplant recipients and genotype 1 or 4 SVR12 by subgroup, ITT population Genotype (N) Cirrhosis Regimen, duration SVR12 Cohort 3 Liver transplant Genotype 1a (N = 4) Yes OBV/PTV/r + DSV + RBV 24 weeks 100% Genotype 1b (N = 2) OBV/PTV/r + DSV ± RBV 12 weeks Cohort 4 Genotype 1a (N = 22) No 95% * Genotype 1b (N = 12) OBV/PTV/r + DSV Cohort 5 Renal transplant Genotype 1a (N = 9) 67% ** Genotype 1b (N = 3) Cohort 6 Genotype 4 (N = 2) OBV/PTV/r + RBV Genotype 4 (N = 1) * 1 virologic failure ; ** 3 premature discontinuations CORAL-I , cohorts 3-6 Agarwal K, EASL 2017, Abs. FRI-267 3

4 ARV-trial.com CORAL-I study cohorts 3 to 6: OBV/PTV/r + DSV + RBV in transplant recipients and genotype 1 or 4 Adverse events, % Genotype 1 Genotype 4 Cohort 3 LT, cirrhosis N = 6 Cohort 4 LT, no cirrhosis N = 34 Cohort 5 RT, no cirrhosis N = 12 Cohort 6 LT N = 3 Any adverse event 100 92 AE leading to discontinuation * 3 17 Serious AE 9 33 Death ** 8 AE in ≥ 10% of patients Fatigue Pruritus Headache Nausea Diarrhea Insomnia * Nausea and vomiting leading to withdrawal of consent (N = 1), atypical pneumonia with acute renal injury followed by acute respiratory failure (N = 1), and tacrolimus overdose (N = 1) ** 1 patient (tacrolimus overdose) CORAL-I , cohorts 3-6 Agarwal K, EASL 2017, Abs. FRI-267 4

5 Laboratory abnormalities, %
ARV-trial.com CORAL-I study cohorts 3 to 6: OBV/PTV/r + DSV + RBV in transplant recipients and genotype 1 or 4 Laboratory abnormalities, % Genotype 1 Genotype 4 Cohort 3 LT, cirrhosis N = 6 Cohort 4 LT, no cirrhosis N = 34 Cohort 5 RT, no cirrhosis N = 12 Cohort 6 LT N = 3 Hemoglobin g/dL < 6.5 g/dL 10 6 8 Total bilirubin > x ULN > 10 x ULN 12 ALT > 5-20 x ULN > 20 x ULN AST CORAL-I , cohorts 3-6 Agarwal K, EASL 2017, Abs. FRI-267 5

6 CORAL-I study cohorts 3 to 6: OBV/PTV/r + DSV + RBV in transplant recipients and genotype 1 or 4
Summary In liver transplant recipients with or without cirrhosis and infected with HCV genotype 1 or 4, treatment with OBV/PTV/r + DSV + RBV was associated with high SVR12 rates and good tolerability In renal transplant recipients, SVR12 was achieved in 9/12 patients, with 3 premature discontinuations due to adverse events, including 1 fatality Need for tacrolimus dose reduction and therapeutic drug monitoring of tacrolimus levels to manage the interaction with ritonavir Patients with genotype 1b achieved SVR12 of 100% with RBV-free regimens CORAL-I , cohorts 3-6 Agarwal K, EASL 2017, Abs. FRI-267

Download ppt "ARV-trial.com CORAL-I study cohorts 3 to 6: OBV/PTV/r + DSV + RBV in transplant recipients and genotype 1 or 4 Design W12 W24 No randomisation Open-label."

Similar presentations

Kwo PY. NEJM 2014;371:2375-82 CORAL-I  Design OBV/PTV/r + DSV + RBV Open label Phase II 18-70 years Chronic HCV infection, genotype 1 Liver transplantation.

Kwo PY. NEJM 2014;371: CORAL-I  Design OBV/PTV/r + DSV + RBV Open label Phase II years Chronic HCV infection, genotype 1 Liver transplantation.
OBV/PTV/r + DSV + RBV Placebo Randomisation** 3 : 1 Double blind 18-70 years Chronic HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Failure to pre-treatment with.

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.
OBV/PTV/r + DSV + RBV OBV/PTV/r + DSV Randomisation* 1 : 1 Open label 18-70 years Chronic HCV infection Genotype 1b Prior failure to PEG-IFN + RBV HCV.

OBV/PTV/r + DSV + RBV OBV/PTV/r + DSV Randomisation* 1 : 1 Open label years Chronic HCV infection Genotype 1b Prior failure to PEG-IFN + RBV HCV.
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.
OBV/PTV/r Placebo Randomisation** 2 : 1 18-75 years Chronic HCV Genotype 1b HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated, no prior failure with DAA Without.

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.
 Treatment regimens –Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r) : 25/150/100 mg QD = 2 tablets –Dasabuvir (DSV) : 250 mg bid  Objective.

 Treatment regimens –Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r) : 25/150/100 mg QD = 2 tablets –Dasabuvir (DSV) : 250 mg bid  Objective.
TURQUOISE-I OBV/PTV/r + DSV + RBV Randomisation* 1 : 1 Open-label 18-70 years HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated with PEG-IFN +

TURQUOISE-I OBV/PTV/r + DSV + RBV Randomisation* 1 : 1 Open-label years HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated with PEG-IFN +
 Treatment regimens –Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r) : 25/150/100 mg QD = 2 tablets –Dasabuvir (DSV) : 250 mg BID –RBV.

 Treatment regimens –Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r) : 25/150/100 mg QD = 2 tablets –Dasabuvir (DSV) : 250 mg BID –RBV.
No randomization N = 59 W12W24 Arm B : compensated cirrhosis N = 31 N = 29 Arm C : compensated cirrhosis Arm A : No cirrhosis AGATE-II Study: OBV/PTV/r.

No randomization N = 59 W12W24 Arm B : compensated cirrhosis N = 31 N = 29 Arm C : compensated cirrhosis Arm A : No cirrhosis AGATE-II Study: OBV/PTV/r.
Asselah T. AASLD 2015, Abs. 714 Randomisation 1:1 Open-label 18-65 years HCV genotype 4 HCV RNA ≥ 1,000 IU/ml Naïve or pre-treated with PEG-IFN + RBV (Part.

Asselah T. AASLD 2015, Abs. 714 Randomisation 1:1 Open-label years HCV genotype 4 HCV RNA ≥ 1,000 IU/ml Naïve or pre-treated with PEG-IFN + RBV (Part.
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.
 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.
 Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI, by ITT, descriptive analysis OBV/PTV/r + DSV + RBV No randomisation Open-label CORAL-I Study cohort.

 Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI, by ITT, descriptive analysis OBV/PTV/r + DSV + RBV No randomisation Open-label CORAL-I Study cohort.
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.
 Objective –SVR 12 (HCV RNA < 25 IU/ml), by ITT OBV/PTV/r + DSV + SOF +RBV Open-label W24 ≥ 18 years Chronic HCV Genotype 1 Prior failure on DAA-regimen.

 Objective –SVR 12 (HCV RNA < 25 IU/ml), by ITT OBV/PTV/r + DSV + SOF +RBV Open-label W24 ≥ 18 years Chronic HCV Genotype 1 Prior failure on DAA-regimen.
Dore G. J Hepatol 2016; 64:19-28 MALACHITE TVR + PEG-IFN + RBV Randomisation Open-label 18-65 years HCV genotype 1 HCV RNA > 10,000 IU/ml Naïve (MALACHITE-I)

Dore G. J Hepatol 2016; 64:19-28 MALACHITE TVR + PEG-IFN + RBV Randomisation Open-label years HCV genotype 1 HCV RNA > 10,000 IU/ml Naïve (MALACHITE-I)
 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

Similar presentations

Ads by Google