OPTIMIST-1

OPTIMIST-1 Study: SMV + SOF for genotype 1 and no cirrhosis
A Phase 3, Randomised, Open-Label Study to Evaluate the Efficacy and Safety of 12 and 8 Weeks of Simeprevir (SMV) plus Sofosbuvir (SOF) in Treatment-Naïve and -Experienced Patients with Chronic HCV Genotype 1 Infection without Cirrhosis: OPTIMIST-1
Kwo P. Hepatology. 2016 Aug; 64:370-80

Anti-HCV
Simeprevir
Sofosbuvir
Genotype
1
1a
1b
Treatment history
Naive
IFN-Experienced
Cirrhosis
No

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Design


* Randomisation was stratified on genotype (1a with Q80K or 1a without Q80K or 1b), IL28B (CC or non-CC) and prior HCV treatment history (naïve/relapse or non-response or other)

Objective

  • SVR12 : superiority of SMV + SOF vs historical control of approved DAA + PEG-IFN + RBV regimens (composite SVR12 of 83% for 8 weeks and 87% for 12 weeks, with a lower limit of the 95% CI > SVR12 of historical control). If superiority, assessment of non-inferiority of 8 vs 12 weeks of SMV + SOF. Analyses by ITT

Baseline characteristics and patient disposition

SVR12 (HCV RNA < 25 IU/ml), % (95% CI), intent -to- treat


*Not superior to historical control
** Superior to historical control

SVR12 (HCV RNA < 25 IU/ml), %, intent -to- treat


No impact of race, ethnicity, BMI on SVR

Relapses, overall and according to sub-groups, N (%)

Resistance testing (population sequencing) of 28 relapses

  • Resistance emergence to SMV, N = 2 (R155K + D1682 + I170T ; I170T)
  • Resistance to SOF (S282T) in 1/25 relapses in the 8-week arm

Adverse events, N (%)

Laboratory abnormalities, N (%)

Summary

  • In HCV genotype 1- infected treatment-naïve and treatment-experienced patients without cirrhosis, 12 weeks of SMV + SOF led to SVR12 rates of 97% overall, and demonstrated superiority over the historical control
    • 8 weeks of SMV + SOF led to SVR12 rates of 83% overall, and did not achieve superiority compared with the historical control
  • In the 12-week arm, SVR12 = 92% were observed in all subgroups, including those with baseline characteristics historically associated with a poor response to HCV treatment (non-CC IL28B genotype, high HCV RNA at baseline, genotype 1a [ with or without Q80K])
  • In the 8-week arm, high SVR12 rates were observed in patients with baseline HCV RNA < 4 million IU /ml (96%), genotype 1b ( 92%) and IL28B CC genotype (93%)
  • Patients in the 8-week arm with baseline HCV RNA < 4 million IU /ml had low relapse rates (4%)
  • Treatment with SMV+SOF for 12 or 8 weeks was safe and well tolerated, with no discontinuations due to adverse events
  • Patient-reported symptoms and quality of life significantly improved from baseline to the SVR12 time point in both treatment arms