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

Slides:

Advertisements

Similar presentations

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:

Advertisements

No HBV or HIV co-infection

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.

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 : years Chronic HCV Genotype 1b HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated, no prior failure with DAA Without.

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.

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.

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-

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.

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.

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.

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

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

eGFR (MDRD) > 50 mL/min

Phase 3 Treatment Experienced

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3

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

Design Randomisation 1 : 1 Double-blind W8 W12

Design Single arm Open label W12 ≥ 18 years, HCV genotype 1 to 6

No HBV or HIV co-infection

TOPAZ-II Study: OBV/PTV/r + DSV + 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.

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

Design Randomisation 2 : 1 Double-blind W12 ≥ 18 years, HCV genotype 3

No HBV or HIV co-infection

GEODE-II Study: OBV/PTV/r + DSV + low dose RBV in genotype 1a

GARNET Study: OBV/PTV/r + DSV 8 weeks in genotype 1b

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

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

AL study: AL ODV + SMV in naïve patients, 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

LDV/SOF in kidney transplant recipients

Design W12 W16 Randomisation Open-label ≥ 18 years HCV genotype 1 or 4

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

ARV-trial.com IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease Design Open label ≥ 18 years Chronic HCV infection Genotype.

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

LEPTON Study: SOF/VEL + GS-9857 genotype 1 or 3 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.

No HBV or HIV co-infection

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

Design W12 W16 Randomisation Open-label ≥ 18 years HCV genotype 1 or 4

SOF/VEL ± RBV in genotype 3 with compensated cirrhosis

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

ENDURANCE-4 Study: glecaprevir/pibrentasvir in genotype 4, 5 or 6

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.

Design W12 Open-label Liver transplant recipients

Presentation transcript:

GS-US-367-1169 Study: SOF/VEL + GS-9857 in genotype 2, 3, 4 or 6 - Phase II Design Open-label W6 W8 W12 No cirrhosis SOF/VEL + GS-9857 N = 33 > 18 years Genotype 2, 3, 4, 5 or 6 HCV RNA > 10 000 IU/mL Treatment-naive or treatment-experienced (with or without DAA) Compensated cirrhosis allowed Creatinine clearance > 60 mL/min No HBV or HIV co-infection Naive N = 30 SOF/VEL + GS-9857 Cirrhosis No cirrhosis SOF/VEL + GS-9857 N = 36 Treatment- experienced N = 29 SOF/VEL + GS-9857 Cirrhosis SOF/VEL: 400/100 mg FDC QD ; GS-9857: 100 mg QD Objective SVR12 (HCV RNA < 15 IU/mL), by ITT, with 2-sided 95% CI (no inferential statistics) GS-US-367-1169 Gane EJ, Gastroenterology 2016; 151:902-909

Baseline characteristics Treatment-experienced GS-US-367-1169 Study: SOF/VEL + GS-9857 in genotype 2, 3, 4 or 6 - Phase II Baseline characteristics Treatment-naive Treatment-experienced No cirrhosis Cirrhosis SOF/VEL + GS-9857 6W N = 33 8W N = 30 12W N = 36 N = 29 Age, years, mean 53 56 57 58 Female, % 64 30 28 White, % 82 80 81 79 HCV RNA, log10 IU/mL, mean 6.2 6.1 6.3 6.4 IL28B CC, % 33 37 42 35 Genotype 1b / 2 / 3 / 4 / 6, N 1 / 6 / 21 / 5 / 0 0 / 6 / 18 / 5 / 1 0 / 13 / 18 / 4 / 1 0 / 8 / 17 / 3 / 1 DAA experience, N None SOF + RBV + PEG-IFN Other DAAs - 17 14 5 10 17 2 GS-US-367-1169 Gane EJ, Gastroenterology 2016; 151:902-909

Treatment-experienced GS-US-367-1169 Study: SOF/VEL + GS-9857 in genotype 2, 3, 4 or 6 - Phase II SVR12, ITT, % (95% CI) Treatment-experienced 20 40 60 80 100 88 ( 72-97) 33 (90-100) 36 % N= 97 (82-99) 29 Naive No cirrhosis 93 ( 78-99) 30 Cirrhosis SOF/VEL + GS-9857 6W 8W 12W GS-US-367-1169 Gane EJ, Gastroenterology 2016; 151:902-909

SVR12 and relapse by genotype Treatment-experienced GS-US-367-1169 Study: SOF/VEL + GS-9857 in genotype 2, 3, 4 or 6 - Phase II SVR12 and relapse by genotype Treatment-naive Treatment-experienced No cirrhosis Cirrhosis SOF/VEL + GS-9857 6W N = 33 8W N = 30 12W N = 36 N = 29 SVR12, N (%) Genotype 1b 1 (100) Genotype 2 4/6 (67) 6/6 (100) 13/13 (100) 8/8 (100) Genotype 3 21/21 (100) 17/18 (94) 18/18 (100) 16/17 (94) Genotype 4 3/5 (60) 4/5 (80) 4/4 (100) 3/3 (100) Genotype 6 1/1 (100) Relapse, N (%) 4 (12) 2 (7) 1 (3) GS-US-367-1169 Gane EJ, Gastroenterology 2016; 151:902-909

SVR12 according to presence or absence of baseline RASs GS-US-367-1169 Study: SOF/VEL + GS-9857 in genotype 2, 3, 4 or 6 - Phase II Resistance analysis (1% deep sequencing) At baseline, presence of class RASs (NS3, NS5A or NS5B) 32/63 (51%) treatment-naïve patients 6/27 (22%) IFN-experienced, DDA-naïve 20/38 (53%) DDA-experienced patients SVR12 according to presence or absence of baseline RASs Population Duration of SOF/VEL + GS-9857 SVR12 Baseline RASs Yes No Naive, no cirrhosis 6 weeks 11/14 (79%) 18/19 (95%) Naive, cirrhosis 8 weeks 11/12 (92%) 17/18 (94%) DAA-experienced 12 weeks 23/24 (96%) 41/41 (100%) At relapse, N = 7 Emergence of RAS in 1 patient with genotype 3a: Y93H at baseline and relapse, emergence of Q80R GS-US-367-1169 Gane EJ, Gastroenterology 2016; 151:902-909

Treatment-experienced GS-US-367-1169 Study: SOF/VEL + GS-9857 in genotype 2, 3, 4 or 6 - Phase II Adverse events, % Treatment-naive Treatment-experienced No cirrhosis Cirrhosis SOF/VEL + GS-9857 6W N = 33 8W N = 30 12W N = 36 N = 29 Serious adverse event 3 AE leading to discontinuation 7 Death AE in ≥ 5% of patients Headache Diarrhea Fatigue Nausea Constipation Dizziness Dry mouth Abdominal pain, upper Nasopharyngitis Upper respiratory tract infection 30 30 21 27 3 9 6 6 3 6 10 3 10 10 7 0 3 3 3 3 31 28 28 22 6 0 0 3 0 3 28 28 21 14 3 10 10 3 10 3 GS-US-367-1169 Gane EJ, Gastroenterology 2016; 151:902-909

Laboratory abnormalities, N (%) Treatment-experienced GS-US-367-1169 Study: SOF/VEL + GS-9857 in genotype 2, 3, 4 or 6 - Phase II Laboratory abnormalities, N (%) Treatment-naive Treatment-experienced No cirrhosis Cirrhosis SOF/VEL + GS-9857 6W N = 34 8W N = 33 12W N = 31 N = 32 Hemoglobin 7-9 g/dl 1 (3) Neutrophils 500-750/mm3 Platelets 25 000-50 000/mm3 Creatine kinase > 20 x ULN Glycemia 3-4 g/L Lipase < 3 x ULN 3 (10) GS-US-367-1169 Gane EJ, Gastroenterology 2016; 151:902-909

GS-US-367-1169 Study: SOF/VEL + GS-9857 in genotype 2, 3, 4 or 6 - Phase II Summary In this phase 2 open-label trial, SOF/VEL + GS-9857 (8 weeks in treatment-naïve patients or 12 weeks in treatment- experienced patients) was safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis GS-US-367-1169 Gane EJ, Gastroenterology 2016; 151:902-909