Presentation is loading. Please wait.

Presentation is loading. Please wait.

ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Randomisation 1 : 1 Open-label.

Published byGlenna Liani Hermanto Modified over 5 years ago

Similar presentations

Presentation on theme: "ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Randomisation 1 : 1 Open-label."— Presentation transcript:

1 ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Randomisation 1 : 1 Open-label W12 W24 Design 18-70 years HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated with PEG-IFN + RBV HIV infection, on ATV/r or RAL (Part 1a) or DRV/r (Part 1b) HIV RNA < 40 c/ml and CD4 ≥ 200/mm3 Cirrhosis Child-Pugh A allowed No HBV co-infection N = 31 OBV/PTV/r + DSV + RBV Part 1a * OBV/PTV/r + DSV + RBV N = 32 N = 10 ** Part 1b OBV/PTV/r + DSV + RBV OBV/PTV/r + DSV + RBV N = 12 *** * Randomisation stratified on prior PEG-IFN + RBV therapy, and cirrhosis ; naïve patients also stratified on IL-28B (CC vs non-CC); experienced patients also stratified on prior response (null, partial, relapse) ** DRV 800 mg qd (ritonavir stopped) ; *** DRV 600 mg bid + ritonavir 100 mg qd 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 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) Primary efficacy endpoint SVR12 (HCV RNA < 25 IU/ml), with 2-sided 95% CI, comparison between groups TURQUOISE-I Sulkowski MS, JAMA 2015;315: ; Wyles D. J Infect Di 2017; 215: 1

2 Baseline characteristics and patient disposition (Part 1a)
ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Baseline characteristics and patient disposition (Part 1a) 12 weeks N = 31 24 weeks N = 32 Mean age, years 50.9 Female 6% 9% Body mass index, mean 26.4 27.2 Genotype : 1a / 1b 87% / 13% 91% / 9% IL28B non-CC genotype 84 % 78 % HCV RNA log10 IU/ml, mean (SD) 6.54 ± 0.57 6.60 ± 0.78 Fibrosis score F0-F1 / F2 / F3 / F4 (%) 52 / 16 / 13 / 19 63 / 16 / 3 / 19 Prior treatment with PEG-IFN + RBV, N (%) 11 (35%) 10 (31%) Null response 5 Partial response 2 Relapse 1 3 CD4/mm3, mean 633 625 ARV regimen : ATV/r / RAL 52% / 48% 38% / 63% Discontinued treatment, N (withdrew consent) (virologic breakthrough) TURQUOISE-I Sulkowski MS, JAMA 2015;315: 2

3 Virologic Outcome (Part 1a) 1 virologic breakthrough
ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Virologic Outcome (Part 1a) 12 weeks N = 31 24 weeks N = 32 SVR12 (HCV RNA < 25 IU/ml) 94% (95% CI: ) 91 % (95% CI : ) Failure*, N Reasons 2 1 consent withdrawn 1 relapse 3 1 virologic breakthrough 2 re-infection Mutations detected Relapse NS3 : D168V NS5A : M28T NS5B : S556G Breakthrough NS3 : R155K NS5A : Q30R Prior PEG-IFN + RBV therapy in failures Naïve = 1, Null response = 1 Naïve = 2, Null response = 1 Fibrosis stage in failures F3 / F4 F4 / F0-F1 / F0-F1 * All 5 = genotype 1a No HIV RNA failure (3 blips in W12-group and 5 blips in W24-group) Decrease in absolute but not relative CD4 cell counts TURQUOISE-I Sulkowski MS, JAMA 2015;315: 3

4 Adverse events, Part 1 a, n (%)
TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Adverse events, Part 1 a, n (%) 12 weeks, N = 31 24 weeks, N = 32 AE leading to treatment discontinuation AE leading to RBV dose reduction 5 6 Serious adverse event AE occurring in > 10% in either group Fatigue 58% 38% Insomnia 16% 22% Nausea 19% Headache 13% Upper respiratory tract infection Pruritus 6% Cough 7% Ocular icterus 3% Diarrhea Hyperbilrubinemia ALT > 5 x ULN / AST > 5 x ULN 0 / 0 0 / 1 Total bilirubin > 3 x ULN 35% TURQUOISE-I Sulkowski MS, JAMA 2015;315:

5 Baseline characteristics and SVR12 (Part 1b)
ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Baseline characteristics and SVR12 (Part 1b) OBV/PTV/r + DSV + RBV DRV qd, n = 10 DRV bid, n = 12 Median age, years 56 53 Female, % 20 25 Body mass index, median 26 Genotype 1a, % 90 50 IL28B non-CC genotype, % 100 83 Cirrhosis, % Prior treatment with PEG-IFN + RBV, % 30 DRV as first PI, % 33 CD4/mm3, median 656 612 SVR12 100% HIV RNA blips : 2/10 DRV qd and 3/12 DRV bid TURQUOISE-I Wyles D. Journal Infect Dis 2017 (ePub ahead of print) 5

6 Pharmacokinetic parameters of DRV qd and bid (Part 1b)
ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Pharmacokinetic parameters of DRV qd and bid (Part 1b) OBV/PTV/r + DSV + RBV DRV qd, n = 10 DRV bid, n = 12 Cmax 0.924 0.921 AUC 0.833 0.876 Ctrough 0.643 0.730 Values are the least square mean ratios (90% confidence intervals) for DRV pharmacokinetic parameters with and without OBV/PTV/r + DSV (DRV + OBV/PTV/r + DSV vs DRV alone) TURQUOISE-I Wyles D. J Infect Di 2017; 215: 6

7 1 (colitis and dehydration, not related to study drugs)
TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Adverse events, Part 1 b, n OBV/PTV/r + DSV + RBV DRV qd, n = 10 DRV bid, n = 12 AE leading to treatment discontinuation Serious adverse event 1 (colitis and dehydration, not related to study drugs) AE occurring in > 15% in either group Fatigue 4 Hemoglobin decreased 1 Irritability 3 2 Nausea ALT > 5 x ULN / AST > 5 x ULN 0 / 0 Total bilirubin > 3 x ULN Hemoglobin 8-10 g/dl, < 8 g/dl 1 / 0 3 / 1 RBV dose reduction, n = 9 (decrease hemoglobin levels, n = 4 ; anemia, n = 3 ; fatigue, n = 2) TURQUOISE-I Wyles D. J Infect Di 2017; 215:

8 ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Summary In Part 1a of this open-label, randomised uncontrolled study, treatment with the all-oral, IFN-free 3D plus ribavirin regimen resulted in high SVR12 rates among patients co-infected with HCV genotype 1 and HIV-1 whether treated for 12 or 24 weeks No discontinuation for AE The 2 failures (1 virologic breakthrough and 1 relapse) were observed in patients with genotype 1a and F4 fibrosis Limitations Small sample size ARV therapy limited to ATV/r- or RAL-containing regimens Role of RBV not addressed In Part 1b, HCV genotype 1 HIV-1 coinfected patients on stable DRV-containing ART achieved 100% SVR12 while maintaining plasma HIV-1 RNA suppression. Despite DRV Ctrough decrease, episodes of intermittent HIV-1 viremia were infrequent TURQUOISE-I Sulkowski MS, JAMA 2015;315: ; Wyles D. J Infect Di 2017; 215: 8

Download ppt "ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Randomisation 1 : 1 Open-label."

Similar presentations

VALENCE SOF + RBV Not randomised Open label* ≥ 18 years Chronic HCV infection Genotype 2 or 3 HCV RNA ≥ 10,000 IU/ml Treatment naïve or prior IFN-based.

VALENCE SOF + RBV Not randomised Open label* ≥ 18 years Chronic HCV infection Genotype 2 or 3 HCV RNA ≥ 10,000 IU/ml Treatment naïve or prior IFN-based.
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.
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%,

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%,
ELECTRON  Design SOF + RBV Randomisation* 1 : 1 : 1 : 1 Open-label ELECTRON Study: SOF-based therapy for genotypes 1, 2 and 3 W8W4W12 ≥ 19 years Chronic.

ELECTRON  Design SOF + RBV Randomisation* 1 : 1 : 1 : 1 Open-label ELECTRON Study: SOF-based therapy for genotypes 1, 2 and 3 W8W4W12 ≥ 19 years Chronic.
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.
No prior therapy with PI

No prior therapy with PI
OBV/PTV/r Open label 18-70 years Chronic HCV infection Genotype 1b Treatment-naïve or failure to PEG-IFN + RBV HCV RNA > 10,000 IU/ml Without or with cirrhosis*

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*
FUSION  Design  Objectives –SVR ≥ 20% compared with historical control of 25%, 97% power –Difference of SVR > 20% between the 2 groups, 82% power SOF.

FUSION  Design  Objectives –SVR ≥ 20% compared with historical control of 25%, 97% power –Difference of SVR > 20% between the 2 groups, 82% power SOF.
FISSION  Design  Objective –Non inferiority of SOF + RBV : SVR 12 (2-sided significance level of 5%, lower margin of the 95% CI for the difference =

FISSION  Design  Objective –Non inferiority of SOF + RBV : SVR 12 (2-sided significance level of 5%, lower margin of the 95% CI for the difference =
AI444040 Study  Design SOF 1W then DCV + SOF 23W DVC + SOF Randomisation* 1 : 1 : 1 Open-label AI444040 Study: DCV + SOF + RBV for genotypes 1, 2 and.

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.
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.
OBV/PTV/r + DSV + RBV OBV/PTV/r + DSV + placebo Randomisation* Partial blind 18-70 years Chronic HCV infection Genotype 1 Treatment-naïve HCV RNA > 10,000.

OBV/PTV/r + DSV + RBV OBV/PTV/r + DSV + placebo Randomisation* Partial blind years Chronic HCV infection Genotype 1 Treatment-naïve HCV RNA > 10,000.
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.

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.
Reddy KR. Lancet Infect Dis. 2015;15:27-35 ATTAIN SMV + TVR placebo + PEG-IFN + RBV TVR + SMV placebo + PEG-IFN + RBV Randomisation* 1 : 1 Double-blind.

Reddy KR. Lancet Infect Dis. 2015;15:27-35 ATTAIN SMV + TVR placebo + PEG-IFN + RBV TVR + SMV placebo + PEG-IFN + RBV Randomisation* 1 : 1 Double-blind.
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.

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.
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.

Similar presentations

Ads by Google