RUBY-I

RUBY-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir ± RBV for HCV genotype 1 with renal impairment
RUBY-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir ± RBV for HCV genotype 1 with renal impairment
Pockros PJ. Gastroenterology 2016 ; 150:1590-8

Anti-HCV
Paritaprevir/ritonavir
Ombitasvir
Dasabuvir
Ribavirin
Genotype
1
1a
1b
Treatment history
Naive
Cirrhosis
No
Special population
Chronic Kidney disease

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Design


** Liver biopsy ( Metavir = F3, Ishak score = 4) or fibroscan < 12.5 kPa or FibroTest = 0.72 + APRI = 2

Treatment regimens

  • Co-formulated ombitasvir (OBV)/ paritaprevir (PTV)/ rironavir (r): 25/150/100 mg qd = 2 tablets
  • Dasabuvir (DSV): 250 mg bid
  • RBV 200 mg qd (genotype 1a)

Objective

  • SVR12 ( HCV RNA < 25 IU/ml ) by intent-to-treat with 2-sided 95% CI

Baseline characteristics and outcome


* 2 failures

  • 1 Genotype 1a, 60 year old male on hemodialysis and history of hypertesnsion , died at D14 after the end of treatment (unrelated cardiac cause) ; HCV RNA undetectable at the end of treatment
  • 1 relapse : black male on hemodialysis, 49, GT1a, F3, IL28B CT, RBV discontinued at D58 due to anemia, compliance not optimal, RAVs emergence at failure : NS3 (D168V) and NS5A (Q30R)

Adverse events and laboratory abnormalities, N (%)

Plasma trough concentrations for study drugs (ng/ml), geometric mean and 95% CI

Time interval > 22-26 hours for PTV, RTV and OBV, and > 10-14 hours for DSV, DSV M1 and RBV

  • C trough geometric means
    • Comparable for PTV, RTV, OBV and DSV in patients with stage 4 and 5 CKD and patients without end-stage renal disease (data from phase 3 studies)
    • 15-38% lower for DSV M1
    • 27-36% lower for RBV
  • Intensive PK in 1 patient on hemodialysis : concentrations of all anti-HCV comparable prior to the start of hemodialysis

Summary

  • In HCV genotype 1-infected patients with stage 4 or 5 chronic kidney disease, including patients on dialysis, 12 weeks of therapy achieved a SVR12 of 90% overall
  • Among patients with post-treatment data available, the SVR12 rate was
    • For genotype 1a : 92.3% (12/13) with OBV/PTV/r + DSV + RBV ; 1 relapse, possibly related to poor treatment compliance
    • For genotype 1b : 100% (7/7) with OBV/PTV/r + DSV
  • OBV/PTV/r + DSV ± RBV was well tolerated with no treatment discontinuations
  • The majority of patients receiving RBV 200 mg/day required RBV interruption (9/13)
  • Laboratory abnormalities and safety findings were otherwise consistent with the safety profile in patients with normal renal function
  • These data support the use of the 3D regimen with no dose adjustment in patients with severe or end-stage renal disease