Ledipasvir-sofosbuvir in Patients With Hepatitis C Virus Genotype 5 Infection: An Open-label, Multicenter, Single-arm, Phase 2 Study

Sol Ahn, Mercer University College of Pharmacy

A systemic review article of 1,217 studies found that hepatitis C virus (HCV) genotype 5 accounts for about 1.4 million cases of HCV infection globally. [1]

A systemic review article of ten clinical studies reports that patients with HCV genotype 5 have relatively low rates of response to pegylated interferon-alfa and ribavirin, with about 60% achieving sustained virological response (SVR) after 48 weeks of therapy. [2]

Ledipasvir-sofosbuvir in Patients With Hepatitis C Virus (HCV) Genotype 5 Infection: An Open-label, Multicenter, Single-arm, Phase 2 Study [3]
Design Prospective, open-label, phase 2 study; N= 41
Objective To investigate the efficacy and safety of combination therapy with the nonstructural protein 5A (NS5A) inhibitor ledipasvir and the nonstructural protein 5B (NS5B) polymerase inhibitor sofosbuvir in patients with HCV genotype 5
Study Groups Treatment naïve (n= 21); treatment experienced (n= 20)
Methods Eligible patients were at least 18 years old and had chronic infection with HCV genotype 5, with plasma HCV ribonucleic acid (RNA) of at least 10,000 IU per milliliters. Study participants were given a fixed-dose combination tablet of 90 mg ledipasvir and 400 mg sofobuvir orally once a day for 12 weeks.
Duration March 7, 2014 to June 10, 2014
Primary Outcome Measure The proportion of patients with a sustained viral response, defined as HCV RNA concentration less than 15 IU per milliliters at 12 weeks
Baseline Characteristics   Treatment naïve (n= 21) Treatment experienced (n= 20)
Age (years) 61 64
Male, n (%) 11 (52%) 10 (50%)
White, n (%) 21 (100%) 20 (100%)
European, n (%) 20 (95%) 19 (95%)
Middle Eastern or North African, n (%) 1 (5%) 1 (5%)
Body-mass index < 30 kg/m2 21 (100%) 17 (85%)
HCV RNA (log10 IU/mL) 6.2 6.6
HCV genotype subtype, 5a, n (%) 20 (95%) 20% (100%)
HCV genotype subtype, unknown, n (%) 1 (5%) 0
Cirrhosis 3 (14%) 6 (30%)
Alanine aminotransferase (U/L) 42 39
Creatinine clearance (mL/min) 85.4 85.1
Results   Treatment naïve (n= 21) Treatment experienced (n= 20)
Viral response after treatment, n (%, 95% CI) 20 (95%, 76-100) 19 (95%, 75-100)
Adverse Events Common Adverse Events: Asthenia (39%), headache (27%), fatigue (10%)
Serious Adverse Events: Depression (2%)
Percentage that Discontinued due to Adverse Events: 0%
Study Author Conclusions The original regimen of ledipasvir-sofosbuvir is an effective and well-tolerated treatment for patients with HCV genotype 5 infection who are treatment naïve or treatment experienced.

In this study, a fixed-dose combination regimen with ledipasvir-sofosbuvir once a day for 12 weeks resulted in SVR in 95% of study participants with HCV genotype 5. The findings of this study also shows that patients who were treatment naïve or treatment experienced were equally likely to reach SVR. A possible limitation of the study includes the fact that all study participants were white and recruited in France, limiting the generalizability of the study result in other patient populations.

References

[1] Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61(1):77-87.

[2] Devaki P, Jencks D, Yee BE, Nguyen MH. Sustained virologic response to standard interferon or pegylated interferon and ribavirin in patients with hepatitis C virus genotype 5: systematic review and meta-analysis of ten studies and 423 patients. Hepatol Int. 2015;9(3):431-7.

[3] Abergel A, Asselah T, Metivier S, et al. Ledipasvir-sofosbuvir in patients with hepatitis C virus genotype 5 infection: an open-label, multicentre, single-arm, phase 2 study. Lancet Infect Dis. 2016;16(4):459-64.

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