Background: Complications from chronic hepatitis C virus (HCV) infection are a major cause of morbidity and mortality among individuals with inherited blood disorders (IBLD). Inability to tolerate ribavirin and frequent comorbidities have limited HCV treatment options in these patients. The aim of the C-EDGE IBLD study was to evaluate the efficacy and safety of a once-daily, fixed-dose combination of elbasvir 50 mg (EBR, an NS5A inhibitor) and grazoprevir 100 mg (GZR, an NS3/4A protease inhibitor) in patients with HCV infection and IBLD, including those with hemoglobinopathies.

Methods: C-EDGE-IBLD was a randomized, double-blind, placebo-controlled study of treatment-naïve and treatment-experienced patients with HCV genotype (GT)1, 4, or 6 infection and IBLD (hemophilia A/B, von Willebrand disease, β-thalassemia, or sickle cell anemia). Patients were randomized in a 2:1 ratio to an immediate-treatment group (ITG; 12 weeks of EBR/GZR) or deferred-treatment group (DTG; 12 weeks of placebo, followed by EBR/GZR for 12 weeks). Randomization was stratified according to the presence of cirrhosis and IBLD diagnosis. The primary endpoints were the proportion of patients in the ITG who achieved sustained virologic response (SVR12, HCV RNA <15 IU/mL 12 weeks after completion of treatment) and a comparison of safety and tolerability between patients receiving EBR/GZR in the ITG vs those receiving placebo in the DTG.

Results: One hundred fifty-nine patients were randomized (ITG, n = 107; DTG, n = 52). Three patients in the DTG did not commence deferred active treatment; therefore, 156 patients received ≥1 dose of EBR/GZR. Mean age was 44 years. Other baseline patient demographics were as follows: 75% male; 18% black; 41% GT1a-infected; 46% GT1b-infected; 11% GT4-infected; 24% cirrhotic; 6% HIV/HCV co-infected; 43% with hemophilia A/B or von Willebrand disease; 38% with β-thalassemia; 18% with sickle cell anemia. SVR12 was achieved by 92.9% (145/156) of patients receiving EBR/GZR (ITG 93.5% [100/107]; DTG 91.8% [45/49]). Of the 11 patients who did not achieve SVR12, 2 discontinued treatment for reasons unrelated to study medication and 9 relapsed, including 7 who had NS5A resistance-associated variants present at baseline. One patient achieved SVR12 but relapsed between follow-up weeks 12 and 24. SVR12 was achieved by 90.8% (59/65), 95.7% (67/70), and 94.4% (17/18) of patients with HCV GT1a, GT1b, and GT4 infection, respectively (2 patients with GT1 non-a,b achieved SVR and the 1 patient with GT6 infection relapsed). SVR 12 was achieved by 96.3% (26/27) of patients with sickle cell anemia, 95% (57/60) with β-thalassemia, and 89.9% (62/69) with hemophilia A/B or von Willebrand disease. During the initial treatment period (EBR/GZR vs placebo), serious adverse events were reported in 3 (2.9%) patients in the ITG (1 drug-related, 2 related to IBLD) and 6 (11.5%) patients receiving placebo in the DTG (1 drug-related, 3 related to IBLD). In the DTG placebo phase, 1 patient discontinued treatment due to an adverse event and 1 patient withdrew consent. No patient in either arm discontinued treatment due to worsening of underlying IBLD. There was 1 hepatic event of clinical interest in each arm (ALT >3× baseline and >100 U/L). In the EBR/GZR treatment phase of the DTG (n = 49), 3 patients reported serious adverse events; none were drug-related and 2 were related to IBLD.

Conclusions: Final data from the C-EDGE IBLD study indicate that EBR/GZR is well tolerated and effective in patients with HCV GT1 or 4 infection with IBLD.

Disclosures

Hézode:BMS: Consultancy; Janssen: Consultancy; MSD: Consultancy; AbbVie: Consultancy; Gilead: Consultancy. Fried:NIH: Research Funding; Gilead: Consultancy, Research Funding; TARGET PharmaSolutions: Equity Ownership; Merck: Consultancy, Research Funding; BMS: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding. Colombo:Merck: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Tibotec: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Vertex: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen Cilag: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Lundbeck: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GenSpera: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AlfaWasserman: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jennerex: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Intercept: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bourlière:MSD: Consultancy; AbbVie: Consultancy; Gilead: Consultancy; Janssen: Consultancy; GSK: Consultancy; BMS: Consultancy. Ben-Ari:Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Strasser:MSD/Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Norgine: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Honoraria. Perumalswami:Merck: Research Funding; Gilead: Research Funding. Zamor:Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Lee:Eli Lilly: Consultancy; BMS: Research Funding; Gilead: Research Funding; Sanofi: Consultancy; Merck: Research Funding; Novartis: Consultancy. Satoskar:Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Research Funding. Sherman:AbbVie: Research Funding; Gilead: Research Funding; BMS: Research Funding; Merck: Consultancy, Research Funding. Morgan:Merck & Co., Inc.: Employment, Equity Ownership. Qiu:Merck: Employment. Hwang:Merck: Employment, Equity Ownership. Robertson:Merck: Employment, Equity Ownership. Nguyen:Merck: Employment. Barr:Merck: Employment, Equity Ownership. Wahl:Merck: Employment. Haber:Merck: Employment. Chase:Merck: Employment. Talwani:Merck & Co., Inc: Employment. Di Marco:Gilead: Research Funding.

Topics:
elbasvir, grazoprevir, hematological diseases, hepatitis c, chronic, infections, adverse event, hemophilia a, sickle cell anemia, thalassemia, von willebrand disease

Author notes

*

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© 2016 by The American Society of Hematology
2016
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