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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%,

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Presentation on theme: "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%,"— Presentation transcript:

1 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%, 90% power SOF + PEG-IFN + RBV SOF + PEG-IFN + RBV** Randomisation* 1 : 2 : 3 Open-label * Randomisation was stratified on IL28 genotype (CC or non-CC) and HCV RNA (< or ≥ 800,000 IU/ml) ** Genotypes 4 and 6 received SOF + PEG-IFN + RBV for 24 weeks *** Randomisation to extension phase only if HCV RNA < 15 IU/ml at W4 ATOMIC Study: SOF + PEG-IFN  -2a + RBV for HCV genotypes 1, 4, 6 W12 W24 N = 125 N = 52 ≥ 18 years Chronic HCV infection Genotype 1, 4, 6 Treatment-naïve HCV RNA ≥ 50,000 IU/ml No cirrhosis No HBV or HIV co-infection –SOF : 400 mg qd ; PEG-IFNα-2a : 180 μg SC once weekly –RBV weight based (bid dosing) : 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg Kowdley KV. Lancet 2013;381:2100-7 SOF + PEG-IFN + RBV SOF + RBV*** SOF*** N = 156 Genotype 1

2 ATOMIC Study: SOF + PEG-IFN  -2a + RBV for HCV genotypes 1, 4, 6 SOF + PR 12W N = 52 SOF + PR 24W N = 125 SOF + PR 12W + extension N = 155 Mean age, years5150 Female33%42%32% Body mass index, mean27.227.628.4 HCV genotype 1a / 1b / 4 / 6 (%)77 / 23 / 0 / 068 / 19 / 9 / 475 / 25 / 0 / 0 IL28B CC genotype25%29%25% HCV RNA log 10 IU/ml, mean (SD) 6.5 ± 0.76.3 ± 0.76.4 ± 0.8 Discontinued treatment, N For AE 5353 27 18 5 + 12 during extension 3 Completed follow-up48112141 Baseline characteristics and patient disposition ATOMIC Kowdley KV. Lancet 2013;381:2100-7

3 ATOMIC Study: SOF + PEG-IFN  -2a + RBV for HCV genotypes 1, 4, 6 SOF + PR 12W N = 52 SOF + PR 24W N = 125 SOF + PR 12W + extension N = 155 SVR 24 (HCV RNA < 15 IU/ml), ITT 89% 95% CI : 77 to 96 89% 95% CI : 82 to 94 87% 95% CI : 81 to 92 SVR 24, per-protocol 96% 95% CI : 86 to 100 98% 95% CI : 93 to 100 97% 95% CI : 93 to 99 SVR 24 for baseline HCV RNA ≥ 800,000 IU/ml 89%90%87% SVR 24, genotype 4 (N = 11)- 82% 95% CI : 48 to 98 - SVR 24, genotype 6 (N = 5)- 100% 95% CI : 48 to 100 - Relapse post-treatment214 Virologic outcome  Relapses post completion of treatment : 4 by W4, 2 by W8, 1 by W12 –6/7 : IL28B CC  4 additional patients did not complete treatment and had virologic failure  No mutations detected in the 11 patients ATOMIC Kowdley KV. Lancet 2013;381:2100-7

4 Most frequent adverse events, n (%) ATOMIC Study: SOF + PEG-IFN  -2a + RBV for HCV genotypes 1, 4, 6 SOF + PR 12W N = 52 SOF + PR 24W N = 125 SOF + PR 12W + extension SOF 12W N = 75 SOF + PR 12W + extension SOF + RBV 12W N = 75 Fatigue48%50%64%48% Headache27%30%43% Nausea31%34%28%36% Insomnia23%22%19%28% Anemia14%25%17%28% Rash14%21%25% Chills29%20%13%24% Neutropenia23%20%11%19% Decreased appetite14% 20%25% Fever35%12%7%24% Diarrhea21%18%16%9% Arthralgia29%18%7%9% Dizziness15% 5%21% Dyspnea15%14%13%15% ATOMIC Kowdley KV. Lancet 2013;381:2100-7

5 Adverse events and laboratory abnormalities, N (%) ATOMIC Study: SOF + PEG-IFN  -2a + RBV for HCV genotypes 1, 4, 6 SOF + PR 12W N = 52 SOF + PR 24W N = 125 SOF + PR 12W + extension 12W N = 155 AE leading to discontinuation in genotype 1, N (%) 3 (6%)19 (18%)7 (5%) Anemia leading to dose reduction of RBV or treatment interruption 5 (10%)25 (20%)17 (23%) Serious adverse events264 Haemoglobin decreased, grade 333%30%29% White blood cells decreased, grade 3-412%8%3% Neutrophils decreased, grade 3-425%22%17% Platelets decreased, grade 34%< 1% AST, grade 3-44%3%1% ALT, grade 3-44%01% Hyperglycemia, grade 302%3% Total bilirubin, grade 3-40< 1% ATOMIC Kowdley KV. Lancet 2013;381:2100-7

6 ATOMIC Study: SOF + PEG-IFN  -2a + RBV for HCV genotypes 1, 4, 6  Summary –12 week SOF-based regimen is effective for patients with HCV genotypes 1, 4, and 6 –SOF is well tolerated –There is no additional benefit of extending SOF treatment beyond 12 weeks –Furthermore, patients in the groups receiving longer durations of PEG-IFN + RBV generally had higher rates of adverse effects without an increase in efficacy –The uniformly high rates of SVR 24 with SOF plus PEG-IFN + RBV also suggest that there would be no need to tailor either the treatment duration or regimen to individual patients on the basis of early response or baseline characteristics –Limitation : study excluded patients with cirrhosis and those who failed to PI-based treatment ATOMIC Kowdley KV. Lancet 2013;381:2100-7

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