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

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Presentation transcript:

CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1 ARV-trial.com CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1 Design Open-label 20-70 years, Japanese Chronic HCV infection Genotype 1 HCV RNA ≥ 100 000 IU/ml Treatment-naive, or IFN-based pre-treated with non-response or relapse No prior DAA therapy No cirrhosis No HBV or HIV co-infection N = 79 SMV 12W + PEG-IFN + RBV 24-48W * * Response-guided therapy in naive and relapsers ; W48 in non-responders SMV: 100 mg 1 capsule qd PEG-IFNa-2b: 1.5 mg/kg SC once weekly RBV: 600 or 1000 mg/day according to body weight Dosage adjustment of PEG-IFN and RBV permitted Objective Primary efficacy endpoint: SVR12 (undetectable HCV RNA), with 95% CI Safety: 70 patients sufficient to detect a 97% probability of detecting an adverse event of special interest with ≥ 5% incidence CONCERTO-4 Kumada H. Hepatol Research 2015;45:501-13 1

CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1 ARV-trial.com CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1 Baseline characteristics, and disposition Naive N = 24 Relapsers N = 29 Non-responders N = 26 Median age, years 60 53 Female 67 45 50 Genotype 1b, % 100 96.2 IL28B CC genotype, % 90 8 HCV RNA log10 IU/ml, median 6.6 6.5 Metavir stage in patients with biopsy: F1 / F2 / F3, % 83 /17 / 0 67 / 17 /17 71 / 29 /0 Prior therapy, % IFN only PEG-IFN only IFN + RBV PEG-IFN + RBV NA 3.4 96.6 11.5 88.5 Discontinuation, N 3 1 11 CONCERTO-4 Kumada H. Hepatol Research 2015;45:501-13 2

CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1 SVR12 (undetectable HCV RNA IU/ml), % (95% CI), ITT 91.7 (73-99) 100 (88.1-100) 38.5 (20.2-59.4) 20 40 60 80 91.7% 90.9% 2 100% 1 NA 6 4 Met RGT criteria (stop W24) SVR12 in those patients Virologic breakthrough, N Relapse, N 24 29 26 % Naive Relapsers Non-responders CONCERTO-4 Kumada H. Hepatol Research 2015;45:501-13

CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1 ARV-trial.com CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1 Emerging mutations in treatment failure Sequencing analysis of NS3: 17/18 failures (naive = 2, relapser = 1, non-responders = 14) Emerging mutations: 16/17 Most frequent emerging mutations D168V, N = 8 Q80R + D168E, N = 3 D168E, N = 2 R155K, N = 1 D168T, N = 1 Q80K + D168E, N = 1 CONCERTO-4 Kumada H. Hepatol Research 2015;45:501-13 4

CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1 Adverse events (entire treatment period) Naive N = 24 Relapsers N = 26 Non-responders Treatment discontinuation of any study medication due to adverse event SMV only, N 1 Dosage adjustment of PEG-IFN due to AE Temporary interruption / Dose reduction 3 / 11 4 / 4 3 / 9 Dosage adjustment of RBV due to AE 4 / 10 6 / 11 4 / 9 Grade 3-4 adverse events, N 6 5 7 Serious adverse event, N Common adverse events, % Pyrexia Decreased white blood cell count Anemia Malaise Headache Decreased appetite Injection-site reactions Rash Alopecia Arthralgia Decreased neutrophil count Decreased platelet count 75 70.8 45.8 50 45.8 45.8 50 58.3 45.8 45.8 45.8 93.1 55.2 72.4 41.4 41.4 41.4 27.6 27.6 31.0 34.5 27.6 20.7 84.6 50.0 30.8 53.8 50.0 26.9 46.2 38.5 19.2 23.1 26.9 30.8 CONCERTO-4 Kumada H. Hepatol Research 2015;45:501-13

CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1 ARV-trial.com CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1 Summary Treatment with SMV 100 mg qd for 12 weeks in combination with PEG IFN-α-2b + RBV (for 24 or 48 weeks) demonstrated potent antiviral activity and high rates of SVR12 in patients who were treatment-naive or had previously relapsed after IFN-based therapy, with most patients having a shorter treatment duration (24 weeks) Antiviral activity was also demonstrated in some patients who had failed to respond to prior IFN-based therapy SMV was well tolerated in all patients No discontinuation of SMV for adverse event Only 1 case of serious adverse event considered related to SMV (hyperbilirubinemia) Limitation: small sample size for the 3 populations (79 patients in total) CONCERTO-4 Kumada H. Hepatol Research 2015;45:501-13 6