LDV/SOF Japanese Study for Genotype 1 Chronic HCV Infection
Explore the LDV/SOF Japanese Study (GS-US-337-0113) focusing on the treatment of genotype 1 Chronic HCV infection in Japanese patients. The study includes baseline characteristics, treatment regimens, SVR12 rates, and patient outcomes. Findings indicate high SVR rates with LDV/SOF and LDV/SOF + RBV treatments. The study also covers patients with NS5A RAV at baseline, adherence rates, and virological failure cases.
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LDV-SOF Japanese Study: LDV/SOF RBV for genotype 1 in Japanese (GS-US-337-0113) Design Randomisation * 1:1 Open-label W12 20 years, Japanese Chronic HCV infection Genotype 1 HCV RNA 100 000 IU/ml Treatment-naive, or pre-treated Compensated cirrhosis ** allowed Creatinine clearance 1 ml/s No HBV or HIV co-infection N = 171 LDV/SOF SVR12 SVR12 LDV/SOF + RBV N = 170 * Randomisation of naive patients stratified on cirrhosis (yes or no) ; Randomisation of pre-treated patients stratified on cirrhosis and prior response to previous therapy (relapse, non-response, IFN-intolerance) ** Liver biopsy (Metavir F4 or Ishak 5), or Fibroscan > 12.5 kPa LDV/SOF 90/400 mg 1 pill qd RBV (divided dose): 600 mg/d if < 60 kg, 800 mg/d if > 60 to 80 kg, 1000 mg/d if 80 kg Objective Primary endpoint: SVR12(HCV RNA < 25 IU/ml), with 2-sided 95% CI For naive patients without cirrhosis, SVR > 23% of the adjusted historical SVR null rate of 63%, 90% power; For other patients, no statistical hypothesis testing Mikozami M, Lancet Infect Dis 2015;15:645-53 LDV-SOF G1 Japanese
LDV-SOF Japanese Study: LDV/SOF RBV for genotype 1 in Japanese (GS-US-337-0113) Baseline characteristics, and disposition LDV/SOF, N = 171 LDV/SOF + RBV, N = 170 Mean age, years Female, % Genotype 1a / 1b, % IL28B CC genotype, % HCV RNA log10IU/ml, mean Cirrhosis, % Treatment history, % Naive Pre-treated PEG-IFN + RBV PI + PEG-IFN + RBV Other Response to previous treatment Non-response Breakthrough or relapse IFN-intolerance Discontinuation, N 60 60 59 57 4 / 96 50 6.6 24 2 / 98 46 6.6 21 49 51 61 19 19 49 51 54 26 20 33 50 17 0 32 51 17 2 (1 AE, 1 death) Mikozami M, Lancet Infect Dis 2015;15:645-53 LDV-SOF G1 Japanese
LDV-SOF Japanese Study: LDV/SOF RBV for genotype 1 in Japanese (GS-US-337-0113) SVR12(HCV RNA < 25 IU/ml), % (95% CI), ITT LDV/SOF LDV/SOF + RBV 100 100 100 100 100 97.2 98 96.4 % (94.9-100) (95.7-100) (98-100) (95.8-100) (95.9-100) (90.2-99.8) (95-100) (89.8-99.2) 100 80 60 40 20 N = 171 170 83 83 88 87 70 71 0 All All Naive Experienced Naive, no cirrhosis * * p < 0.0001 vs SVR null rate of 63%, for both comparisons Mikozami M, Lancet Infect Dis 2015;15:645-53 LDV-SOF G1 Japanese
LDV-SOF Japanese Study: LDV/SOF RBV for genotype 1 in Japanese (GS-US-337-0113) Patients with NS5A RAV at baseline, N = 76 SVR12in 42/42 on LDV/SOF SVR12in 33/34 on LDV/SOF + RBV 1 virological failure Treatment-naive, genotype 1b, 55-year-old woman without cirrhosis who was receiving LDV/DOF + RBV, relapse by post-treatment W4 after completion of treatment. Adherence rates > 99% for both LDV/SOF and RBV (800 mg daily) Baseline NS5A RAV: Y93H (> 99%) NS5A. No other NS5A RAVs were detected at post-treatment W4 No NS5B RAVs and no treatment-emergent variants were detected in any patient at any timepoint tested Mikozami M, Lancet Infect Dis 2015;15:645-53 LDV-SOF G1 Japanese
LDV-SOF Japanese Study: LDV/SOF RBV for genotype 1 in Japanese (GS-US-337-0113) Adverse events LDV/SOF N = 171 0 0 3 0 0 1 1 1 LDV/SOF + RBV N = 170 2 * 1 2 1 ** 1 ** 0 0 0 Treatment discontinuation due to adverse event, N Death Serious adverse events, N Acute myocardial Infarction Cardiac arrest Hepatocellular carcinoma Oesophageal varices haemorrhage Wrist fracture Common adverse events, % Nasopharyngitis Anemia Headache Pruritus Rash Malaise Stomatitis Nausea Decreased hemoglobin : < 10 g/dl / < 8.5 g/dl, N Lymphocyte count 350-500/mm3, N Neutrophil count 500-750/mm3, N Platelet count 25 000-50 000/mm3, N * drug eruption, N = 1, morbilliform rash, N = 1 ; ** related to study drug 29 2 7 4 3 5 4 3 4 / 1 3 2 1 24 14 9 8 8 5 6 5 10 / 0 1 0 0 Mikozami M, Lancet Infect Dis 2015;15:645-53 LDV-SOF G1 Japanese
LDV-SOF Japanese Study: LDV/SOF RBV for genotype 1 in Japanese (GS-US-337-0113) Summary In this trial, 12 weeks of treatment with the fixed-dose combination of LDV/SOF without RBV was well tolerated and resulted in SVR12 in all 171 patients (100%) treated, including patients typically difficult to treat, including those with cirrhosis, or baseline NS5A RAVs, and those who had previously not responded well to other HCV treatment regimens, including PI-based therapies The addition of RBV to LDV/SOF let to a SVR12of 97%, and was associated with an increased number of patients who had adverse events Limitations of the study Open-label design Absence of an active comparator Mikozami M, Lancet Infect Dis 2015;15:645-53 LDV-SOF G1 Japanese
