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.

Slides:

Advertisements

Similar presentations

Hepatitis web study Hepatitis web study Sofosbuvir + Peginterferon + Ribavirin in Genotype 2 or 3 LONESTAR-2 Phase 2 Treatment Experienced Lawitz E, et.

Advertisements

Hepatitis web study Hepatitis web study Ledipasvir-Sofosbuvir for 8 or 12 weeks in HCV GT1 ION-3 Phase 3 Treatment Naïve Kowdley K, et al. N Engl J Med.

Hepatitis web study Hepatitis web study Sofosbuvir + Ribavirin to Prevent Post-Transplant HCV Recurrence Phase 2 Curry MP, et al. Gastroenterology. 2015;148:100-7.

Hepatitis web study Hepatitis web study Sofosbuvir + Ribavirin in HCV GT 4 Egyptian Ancestry Trial Phase 2 Ruane PJ, et al. J Hepatol. 2015;62:

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: 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%,

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 years Chronic HCV infection Genotype 1b Prior failure to PEG-IFN + RBV HCV.

No prior therapy with PI

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:

COSMOS SOF + SMV + RBV SOF + SMV Randomisation 2 : 1 : 2 : 1* Open-label * Randomisation was stratified on genotype (1a or 1b) in both cohorts, IL28B in.

SMV + PEG-IFN + RBV Open-label W12 W24* or W48* N = years Chronic HCV infection Genotype 4 Treatment-naïve or experienced with relapse or partial.

Randomisation* 2 : 1 Double blind *Randomisation was stratified on genotype (1a or 1b or other) and IL28B genotype (CC, CT or TT) N = 133 N = 260 W24W48.

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 =

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.

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.

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.

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.

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.

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.

W24 ≥ 18 years Chronic HCV infection Genotype 1 Treatment naïve Early fibrosis to compensated cirrhosis No HBV or HIV co-infection N = 10 SOF + weight-based.

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.

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.

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.

Hepatitis web study Hepatitis web study Sofosbuvir + Peginterferon + Ribavirin in Genotype 2 or 3 LONESTAR-2 Phase 2 Treatment Experienced Lawitz E, et.

> 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 = 250 W24 SOF + RBV W12 * Randomisation was stratified on prior treatment (naïve or experienced) and cirrhosis (yes or no) ** Metavir.

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.

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.

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.

Asselah T. AASLD 2015, Abs OSIRIS  Design SMV + PEG-IFN + RBV Open label Chronic HCV infection Genotype 4 Treatment-naïve Mild to moderate fibrosis.

 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-

 Design  Objective –Difference in SVR ≥ 40% between the 2 groups, 99% power SOF + RBV Placebo Randomisation 3 : 1* Double blind HCV infection Genotype.

Hepatitis web study Hepatitis web study Sofosbuvir + Ribavirin to Prevent Post-Transplant HCV Recurrence Phase 2 Curry MP, et al. Gastroenterology. 2014;September.

SAPPHIRE-I Feld JJ. NEJM 2014;370: SAPPHIRE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for genotype 1  Treatment regimens.

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.

Placebo + PR W24 DCV + PR Placebo + PR Yes Dore GJ. Gastroenterology 2015;148: COMMAND GT2/3 COMMAND GT2/3 Study: daclatasvir + PEG-IFN + RBV for.

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)

 Design Randomisation* 2 : 1 Double blind *Randomisation was stratified on genotype (1a vs 1b) and ILB28 genotype (CC or non-CC) N = 134 N = 257 W24W48.

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.

 Design Open-label years Chronic HCV infection Genotype 1 HCV RNA > 10,000 IU/mL HIV co-infection Stable ART* with HIV RNA < 50 c/mL ≥ 24 weeks.

PHOTON-1  Design  Objective –SVR 12 with 2-sided 95% CI, descriptive analysis –Multivariate analyses of predictors of SVR 12 SOF + RBV, N= 114 SOF +

 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.

SOF + RBV GT2 Japanese SOF + RBV Open-label Japanese SOF + RBV Study: SOF + RBV in genotype 2  Design W12 Japanese patients ≥ 20 years Chronic HCV 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.

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

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

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

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

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

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

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

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

No HBV or HIV co-infection

Design W12 Randomisation * Open-label

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

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

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

CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1

Presentation transcript:

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 HCV infection HCV RNA ≥ 50,000 IU/ml No cirrhosis No HBV or HIV co-infection SOF + RBV SOF + RBV + PEG-IFN SOF, N = 10 SOF + RBV + PEG-IFN, N = 10 SOF + RBV, N = 10 SOF + RBV, N = 25 + PEG-IFN 4W + PEG-IFN 8W Genotype 2, 3 Treatment-naïve * Randomisation stratified on genotype (2 or 3) and IL28 (CC or non-CC) Genotype 2, 3 Treatment-naïve No randomisation Genotype 1, No response to prior treatment Genotype 1, Treatment naïve  Objective : SVR 24 with two-sided 95% CI, descriptive analysis N = 10 N = 9 N = 10 N = 11 Gane EJ. NEJM 2013;368:34-44

Drug regimenN Genotype N Female % Age, years mean BMI, kg/m 2 mean HCV RNA, log 10 IU/ml, median IL28B CC SOF + RBV 12W10 2, N = 4 3, N = 6 20% % SOF + RBV 12W + PEG-IFNa-2a 4W 9 2, N = 3 3, N = 6 44% % SOF + RBV 12W + PEG-IFNa-2a 8W 10 2, N = 4 3, N = 6 50% % SOF + RBV + PEG-IFNa- 2a 12W 11 2, N = 4 3, N = 7 18% % SOF 12W10 2, N = 3 3, N = 7 60% % SOF + RBV + PEG-IFNa- 2a 8W 103, N = 1050% % SOF + RBV 12W, no response to prior therapy 10 1a, N = 9 1b, N = 1 30% % SOF + RBV 12W, naïve25 1a, N = 22 1b, N = 3 40% % Baseline characteristics and dosing of medication SOF : 400 mg qd ; RBV weight based (bid dosing) : 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg ; PEG-IFN  -2a : 180  g SC once weekly ELECTRON ELECTRON Study: SOF-based therapy for genotypes 1, 2 and 3 Gane EJ. NEJM 2013;368:34-44

Drug regimenGenotypeN HCV RNA < 15 IU/mL End of treatment % (95% CI) SVR 24 % (95% CI) SOF + RBV 12W % (69-100) SOF + RBV 12W + PEG-IFNa-2a 4W % (66-100) SOF + RBV 12W + PEG-IFNa-2a 8W % (69-100) SOF + RBV + PEG-IFNa-2a 12W % (72-100) SOF 12W % (69-100)60% (26-88) SOF + RBV + PEG-IFNa-2a 8W310100% (69-100)100% (66-100) SOF + RBV 12W, no response to prior therapy1a + 1b10100% (69-100)10% (0-45) SOF + RBV 12W, naïve1a + 1b25100% (86-100)84% (64-96) HCV RNA < 15 IU/ml All patients had HCV RNA < 15 IU/ml at W4 on treatment ELECTRON ELECTRON Study: SOF-based therapy for genotypes 1, 2 and 3 Gane EJ. NEJM 2013;368:34-44

 Resistance testing (sequencing)  4 relapse (2 genotype 2 and 2 genotype 3) in the SOF 12W group  1 patient with S282T mutation (genotype 2b)  No NS5B substitutions in the other 3 patients  15 relapse in genotype 1 patients  No NS5B substitutions  Adverse events  Most common : headache, fatigue, insomnia, nausea, rash, anemia  IFN-free groups : less severe reductions in hemoglobin, no neutropenia, no thrombopenia  SOF monotherapy : mean decrease of 0.54g/dl of hemoglobin ELECTRON ELECTRON Study: SOF-based therapy for genotypes 1, 2 and 3 Gane EJ. NEJM 2013;368:34-44

 Summary –By W4 of treatment, all 95 patients in the study had an undetectable level of HCV RNA –All 50 previously untreated patients with HCV genotype 2 or 3 infection who received 8 or 12 weeks of treatment with SOF + RBV, with or without PEG-IFN-alfa 2a, had a sustained virologic response at 24 weeks after treatment –SOF alone 12W was associated with 40% of relapse, suggesting a role for RBV in genotype 2 or 3 to maintain antiviral response –In genotype 1, SVR was much higher in patients naïve to treatment –There was no discontinuation of SOF or RBV in any group –Sofosbuvir plus ribavirin for 12 weeks may be effective in previously untreated patients with HCV genotype 1, 2, or 3 infection ELECTRON ELECTRON Study: SOF-based therapy for genotypes 1, 2 and 3 Gane EJ. NEJM 2013;368:34-44