8 Weeks Versus 12 Weeks of Elbasvir/Grazoprevir in Treatment-naïve CHC With Mild Fibrosis

Study Overview
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Brief Summary
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Grazoprevir plus elbasvir 12 to 16 weeks is now approved for chronic hepatitis C (CHC) genotype 1, 4, or 6 infection regardless liver disease severity. The current study aims to explore the efficacy and safety of 8-week grazoprevir/elbasvir in HCV-1b patients with mild liver fibrosis

Detailed Description
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Grazoprevir, an HCV nonstructural protein 3/4A (NS3/4A) inhibitor 100 mg, plus elbasvir, an HCV NS5A inhibitor 50 mg fixed dose combination, Zepatier, achieved high SVR12 rates of > 95 % in treatment-naïve, experienced cirrhotic and non-cirrhotic patients with genotype 1, 4, or 6 infection. Zepatier, 12 to 16 weeks, was approved for the treatment of HCV genotype 1 and 4 in Taiwan in December, 2016. An SVR rate of 93 % was demonstrated in treatment-naive, non-cirrhotic (F0-F3) GT1b-infected patients who received 8 weeks of grazoprevir/elbasvir with or without ribavirin in the pooled analysis of C-WORTHY (PN035) and C-EDGE treatment-naive (PN060) trials. Furthermore, truncated treatment period of 8-week grazoprevir/elbasvir could achieve an even higher SVR rate at > 98% for naive HCV G1b patients with mild fibrosis (Fibrosis score 0-2). The study aims to evaluate the efficacy of 8-week regimen with grazoprevir/elbasvir on naïve, HCV G1b patients with mild fibrosis by a randomized clinical trial.

Official Title
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Efficacy of 8 Weeks Versus 12 Weeks of Elbasvir/Grazoprevir in Treatment-naïve Chronic Hepatitis C Genotype 1b Patients With Mild Fibrosis: an Open-label, Randomized, Active Control Trial (EGALITE)

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Zepatier Oral Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment naïve, HCV genotype 1b patients History of chronic HCV infection > 6 months Aged at least 20 years HCV RNA of 10,000 IU/mL or greater Fibroscan examination < 9.5 Kpa Negative serum or urine pregnancy test result (sensitivity of 25 mIU or better) for women with childbearing potential within the 24-hour period before the first dose of study drugs Female patients with childbearing potential must agree to use two reliable forms of effective non-hormonal contraception (i.e., condoms, cervical barriers, intrauterine device, spermicides, or sponge), at least 1 of which must be a physical barrier method, during treatment till end of follow up. A hormonal contraception (in lieu of non-hormonal) plus a physical barrier method can be used after end of treatment. All men with female partners of childbearing potential must use two reliable forms of effective contraception (combined) during treatment and till end of follow up Ability to participate and willingness to give written informed consent and to comply with the study restrictions. Exclusion Criteria: Prior experience of IFN or direct antiviral agents (DAA) Hepatitis B virus or HIV co-infection. Patients with experience of ascites, esophageal varices, or other evidence of hepatic decompensation, and/or hepatocellular carcinoma. History of organ transplantation, except cornea transplantation. Hemoglobulin concentration < 11 mg/dl Platelet count < 75,000/mm3 Albumin < 3 mg/dL History of active malignancy within the last 5 years, with the exception of localized or in situ carcinoma (e.g., basal or squamous cell carcinoma of the skin) Poorly controlled diabetes (Hemoglobin A1c value ≥ 8.5%) and endocrine condition. Total bilirubin >2 mg/dL, unless subject has a documented history of Gilbert's disease. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 8-week arm<br>patients receiving 8 weeks of elbasvir 50 mg/grazoprevir (Zepatier Oral Product)100 mg daily | Drug: Zepatier Oral Product<br>* Grazoprevir, an HCV nonstructural protein 3/4A (NS3/4A) inhibitor 100 mg, plus elbasvir, an HCV NS5A inhibitor 50 mg fixed dose combination,Zepatier Oral Product, will be prescribed for 8-12 weeks<br>* Other names: Zepatier;|
| Active Comparator: 12-week arm<br>patients receiving 12 weeks of elbasvir 50 mg/grazoprevir 100 mg (Zepatier Oral Product) daily | Drug: Zepatier Oral Product<br>* Grazoprevir, an HCV nonstructural protein 3/4A (NS3/4A) inhibitor 100 mg, plus elbasvir, an HCV NS5A inhibitor 50 mg fixed dose combination,Zepatier Oral Product, will be prescribed for 8-12 weeks<br>* Other names: Zepatier;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the rate of subjects with undetectable HCV RNA 12 weeks post end-of-treatment | to determine the treatment efficacy (sustained virological response 12 weeks after treatment, SVR12) of 8 weeks of grazoprevir/elbasvir for naïve HCV G1b patients with mild fibrosis, compared to the SVR12 of a universal 12-week grazoprevir/elbasvir for naïve HCV G1b patients with mild fibrosis (Fibrosis score 0-2 | through study completion, an average of 5.5 months |