C-SURFER

C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease
C-SURFER: Grazoprevir plus Elbasvir in Treatment-Naive and Treatment-Experienced Patients with Hepatitis C Virus Genotype 1 Infection and Chronic Kidney Disease
Roth D. Lancet. 2015 Oct 17;386(10003):1537-45

Anti-HCV
Grazoprevir
Elbasvir
Genotype
1
1a
1b
Treatment history
Naive
IFN-Experienced
Special population
Chronic Kidney disease

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Design


* Randomisation was stratified on diabetes ( yes or no ) and hemodialysis status (yes or no )
** based on eGFR (MDRD equation) : 15-29 ml/min = CKD 4 ; < 15 ml/min = CKD 5

GZR 100 mg qd , EBR 50 mg qd , GZR/EBR 100mg/50 mg fixed dose combination 1 pill qd

Objective

  • SVR12 (HCV RNA < 15 IU/ml) > 45% in immediate and PK groups : reference rate, with 2-sided significance level of 0.05

Baseline characteristics

SVR12 (HCV RNA < 15 IU/ml) , % (95% CI), mITT


* Genotype 1b, non cirrhotic, CKD stage 5, NS5A RAV at baseline : L31M, at failure : L31M + Y93H

Virologic outcome

  • SVR12 (99%) > to historical control (45%), p < 0.001
  • SVR rates similar in patients with unfavourable baseline charcateristics (African American, IL28B non-CC, cirrhosis), and in in all subgroups including haemodialysis and non- haemodialysis

Resistance associated variants at baseline

  • NS3 : 36/112 (32.1%) patients : SVR12 in 36/36
  • NS5A : 17/115 (14.8%) of patients : SVR12 in 16/17

Adverse events and laboratory abnormalities, N (%)


* Erythropoietin use : 23% of GZR + EBR group vs 35% of placebo

Renal function monitored events

Summary

  • Once daily GZR + EBR for 12 weeks achieved SVR12 of 99% for treatment of HCV genotype 1 infection among patients with chronic kidney disease stage 4-5
    • SVR12 of 100% in naïve patients
    • SVR12 of 95% in experienced patients
  • Efficacy was consistent across different subpopulation
    • Genotypes 1a and 1b
    • Diabetes
    • Hemodialysis
  • Failure to achieve SVR12 was rare
    • One patient with genotype 1b relapsed
  • Once daily GZR + EBR for 12 weeks was well-tolerated