Efficacy and Safety of 8-weeks of Glecaprevir/Pibrentasvir in Treatment-Naïve Adults With HCV Genotype 1-6 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) ≤1

Study Overview
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Brief Summary
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A study to evaluate the efficacy and safety of glecaprevir(GLE)/pibrentasvir(PIB) in treatment-naïve participants with chronic hepatitis C virus (HCV) genotypes 1-6 infection and with an aspartate aminotransferase to platelet ratio index (APRI) of less than or equal to 1.

Official Title
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A Single Arm, Open Label, Multicenter Study to Evaluate the Efficacy and Safety of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment Naïve Adults With Chronic Hepatitis C Virus (HCV) Genotypes 1 - 6 Infection and Aspartate Aminotransferase to Platelet Ratio Index (APRI) ≤ 1

Conditions
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Hepatitis C Virus (HCV)

Intervention / Treatment
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* Drug: Glecaprevir/Pibrentasvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hepatitis C virus (HCV) genotype (GT) 1, 2, 3, 4, 5, or 6 infection. Mixed GT and indeterminate GT may be acceptable. Aspartate aminotransferase (AST) to platelet ratio index (APRI) score of less than or equal to 1, at time of screening. Does not have current active hepatitis B virus infection defined as: positive hepatitis B surface antigen (HBsAg), OR hepatitis B virus (HBV) deoxyribonucleic acid (DNA) > lower limit of quantification (LLOQ) in subjects with isolated positive anti-hepatitis B core (HBc) (i.e., negative HBsAg and anti-hepatitis B surface[HBs]) Platelets ≥ 150,000 cells/mm³ Albumin ≥ lower limit of normal (LLN) Positive anti-HCV antibody (Ab) AND plasma HCV ribonucleic acid (RNA) viral load ≥ 1,000 IU/mL at Screening and for at least 6 months before Screening. No past history/evidence of cirrhosis. No history of hepatocellular carcinoma. Hepatitis C virus treatment-naïve (had not received a single dose of any approved or investigational anti-HCV medication). If female, the subject must not be pregnant, breastfeeding, or considering becoming pregnant during the study and for 30 days after the last dose of study drug.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glecaprevir/Pibrentasvir<br>Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks. | Drug: Glecaprevir/Pibrentasvir<br>* Glecaprevir/pibrentasvir 100 mg/40 mg co-formulated tablets taken orally as 3 tablets once a day.<br>* Other names: MAVYRET™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in the Modified Intention-to-Treat Population With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; 15 IU/mL) 12 weeks after the last dose of study drug. The 95% confidence interval (95%CI) was calculated using the Wilson's score method. Efficacy was to be established if the lower bound of the 95%CI was greater than the threshold of 92.4%, based on the historical rate observed in glecaprevir/pibrentasvir registrational studies in treatment-naïve, non-cirrhotic patients (98.4%) minus a margin of 6%. | 12 weeks after the last actual dose of study drug, Week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in the Intention-to-Treat Population With SVR12 | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the LLOQ (15 IU/mL) 12 weeks after the last dose of study drug. The 95% confidence interval was calculated using the normal approximation to the binomial distribution. Efficacy was to be established if the lower bound of the 95%CI was greater than the threshold of 91.4%, based on the mITT threshold minus an expected 1% rate of non-virological SVR failures. | 12 weeks after the last actual dose of study drug, Week 20 | 
| Percentage of Participants With On-treatment Virologic Failure | On-treatment virologic failure was defined as one of the following conditions: confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < 15 IU/mL during the Treatment Period; or confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements > 1 log₁₀ IU/mL above nadir) at any time point during the Treatment Period; or HCV RNA ≥ 15 IU/mL at end of treatment with at least 6 weeks of treatment, where the HCV RNA value must be collected on or after Study Drug Day 36 and study drug duration ≥ 36 days. | Up to 8 weeks | 
| Percentage of Participants With Post-treatment Relapse | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment. | From the end of treatment (Week 8) through 12 weeks after the last dose of study drug (Week 20) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pibrentasvir, Sustained Virologic Response 12 weeks post dosing (SVR12), aspartate aminotransferase, platelet, Aspartate aminotransferase to Platelet Ratio Index (APRI), glecaprevir, chronic hepatitis C virus (HCV), Hepatitis, HCV genotype