An Observational Study on Long-Term Persistence of Resistant Mutations And Durability of Sustained Virological Response in Patients With Chronic Hepatitis C Treated With Direct Acting Antiviral (DAA)- Containing Regimens

Study Overview
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Brief Summary
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This observational long-term follow-up study will assess the persistence of direct acting antiviral (DAA) resistant mutations and the durability of sustained virological response in patients with chronic hepatitis C who have participated in a Roche DAA treatment protocol. Up to 5 scheduled monitoring visits for blood sampling during an observational period of up to 36 months.

Official Title
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A Long-term Monitoring Study to Evaluate the Persistence of Direct Antiviral (DAA) Treatment Resistant Mutations or the Durability of Sustained Virological Response (SVR) in Patients Treated With DAA Containing Regimens for Chronic Hepatitis C Infections (CHC)

Conditions
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Hepatitis C, Chronic

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >/=18 years of age chronic hepatitis C participation in Roche DAA treatment protocol for CHC infection DAA-associated resistant mutations persisting through to last evaluation in donor protocol , or partial viral response or viral load rebound while on RO5024048 treatment, or sustained virological response >/= 20 weeks after last dose of study medication in donor study Exclusion Criteria: For patients participating in DAA resistance monitoring: Initiation of treatment after participation in the donor protocol for which there is evidence of cross-resistance to donor protocol DAA For patients participating in DAA SVR durability: Treatment with any anti-HVC therapy since establishing SVR in the donor study

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With the Detectable HCV Ribonucleic Acid (RNA) Results in Resistance Monitoring Arm at Month 3 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 International Units per milliliter [IU/mL]). | Month 3 | 
| Percentage of Participants With the Detectable HCV RNA Results in Resistance Monitoring Arm at Month 6 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 6 | 
| Percentage of Participants With the Detectable HCV RNA Results in Resistance Monitoring Arm at Month 9 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 9 | 
| Percentage of Participants With the Detectable HCV RNA Results in Resistance Monitoring Arm at Month 12 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 12 | 
| Percentage of Participants With the Detectable HCV RNA Results in Resistance Monitoring Arm at Month 18 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 18 | 
| HCV RNA Levels in Resistance Monitoring Arm at Month 3 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 3 | 
| HCV RNA Levels in Resistance Monitoring Arm at Month 6 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 6 | 
| HCV RNA Levels in Resistance Monitoring Arm at Month 9 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 9 | 
| HCV RNA Levels in Resistance Monitoring Arm at Month 12 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 12 | 
| HCV RNA Levels in Resistance Monitoring Arm at Month 18 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 18 | 
| Mean Systolic Blood Pressure in Resistance Monitoring Arm at Month 3 | Any abnormalities in systolic blood pressure (units: millimeters of Mercury [Hg] [mmHg]) were reported at the discretion of principal investigator. | Month 3 | 
| Systolic Blood Pressure in Resistance Monitoring Arm at Month 6 | Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator. | Month 6 | 
| Systolic Blood Pressure in Resistance Monitoring Arm at Month 9 | Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator. | Month 9 | 
| Mean Systolic Blood Pressure in Resistance Monitoring Arm at Month 12 | Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator. | Month 12 | 
| Mean Systolic Blood Pressure in Resistance Monitoring Arm at Month 18 | Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator. | Month 18 | 
| Mean Diastolic Blood Pressure in Resistance Monitoring Arm at Month 3 | Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator. | Month 3 | 
| Mean Diastolic Blood Pressure in Resistance Monitoring Arm at Month 6 | Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator. | Month 6 | 
| Mean Diastolic Blood Pressure in Resistance Monitoring Arm at Month 9 | Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator. | Month 9 | 
| Mean Diastolic Blood Pressure in Resistance Monitoring Arm at Month 12 | Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator. | Month 12 | 
| Mean Diastolic Blood Pressure in Resistance Monitoring Arm at Month 18 | Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator. | Month 18 | 
| Mean Pulse Rate in Resistance Monitoring Arm at Month 3 | Any abnormalities in pulse rate were reported at the discretion of principal investigator. | Month 3 | 
| Mean Pulse Rate in Resistance Monitoring Arm at Month 6 | Any abnormalities in pulse rate were reported at the discretion of principal investigator. | Month 6 | 
| Mean Pulse Rate in Resistance Monitoring Arm at Month 9 | Any abnormalities in pulse rate were reported at the discretion of principal investigator. | Month 9 | 
| Mean Pulse Rate in Resistance Monitoring Arm at Month 12 | Any abnormalities in pulse rate were reported at the discretion of principal investigator. | Month 12 | 
| Mean Pulse Rate in Resistance Monitoring Arm at Month 18 | Any abnormalities in pulse rate were reported at the discretion of principal investigator. | Month 18 | 
| Percentage of Participants Who Received Anti-HCV Medications in Resistance Monitoring Arm | Percentage of participants who received any anti-HCV medication during the monitoring period was reported. | Up to 18 months | 
| Percentage of Participants With the Detectable HCV RNA Results in SVR Durability Monitoring Arm at Month 6 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 6 | 
| Percentage of Participants With the Detectable HCV RNA Results in SVR Durability Monitoring Arm at Month 12 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 12 | 
| Percentage of Participants With the Detectable HCV RNA Results in SVR Durability Monitoring Arm at Month 24 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 24 | 
| Percentage of Participants With the Detectable HCV RNA Results in SVR Durability Monitoring Arm at Month 36 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 36 | 
| Mean HCV RNA Levels in SVR Durability Monitoring Arm at Month 6 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 6 | 
| Mean HCV RNA Levels in SVR Durability Monitoring Arm at Month 12 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 12 | 
| Mean HCV RNA Levels in SVR Durability Monitoring Arm at Month 24 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 24 | 
| Mean HCV RNA Levels in SVR Durability Monitoring Arm at Month 36 | Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL). | Month 36 | 
| Mean Systolic Blood Pressure in SVR Durability Monitoring Arm at Month 6 | Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator. | Month 6 | 
| Mean Systolic Blood Pressure in SVR Durability Monitoring Arm at Month 12 | Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator. | Month 12 | 
| Mean Systolic Blood Pressure in SVR Durability Monitoring Arm at Month 24 | Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator. | Month 24 | 
| Mean Systolic Blood Pressure in SVR Durability Monitoring Arm at Month 36 | Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator. | Month 36 | 
| Mean Diastolic Blood Pressure in SVR Durability Monitoring Arm at Month 6 | Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator. | Month 6 | 
| Mean Diastolic Blood Pressure in SVR Durability Monitoring Arm at Month 12 | Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator. | Month 12 | 
| Mean Diastolic Blood Pressure in SVR Durability Monitoring Arm at Month 24 | Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator. | Month 24 | 
| Mean Diastolic Blood Pressure in SVR Durability Monitoring Arm at Month 36 | Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator. | Month 36 | 
| Mean Pulse Rate in SVR Durability Monitoring Arm at Month 6 | Any abnormalities in pulse rate were reported at the discretion of principal investigator. | Month 6 | 
| Mean Pulse Rate in SVR Durability Monitoring Arm at Month 12 | Any abnormalities in pulse rate were reported at the discretion of principal investigator. | Month 12 | 
| Mean Pulse Rate in SVR Durability Monitoring Arm at Month 24 | Any abnormalities in pulse rate were reported at the discretion of principal investigator. | Month 24 | 
| Mean Pulse Rate in SVR Durability Monitoring Arm at Month 36 | Any abnormalities in pulse rate were reported at the discretion of principal investigator. | Month 36 | 
| Number of Participants With Danoprevir (DNV) Resistance Status-Population Sequencing | Population sequencing was used for determination of loss of resistance status. Resistance status was reported as either with loss of DNV resistance or without loss of DNV resistance. Results are reported as per donor protocol. Category 1: Number of participants with loss of resistance in NV22688. A total of 99 participants with resistance at the end of donor study by population sequencing were included in this analysis. Category 2: Number of participants with no loss of resistance in NV22688. A total of 33 participants with resistance at the end of donor study by population sequencing were included in this analysis. Category 3: Number of participants with loss of resistance in donor study. A total of 30 participants with no DNV resistance at the end of donor study by population sequencing enrolled in NV22688 were included in this analysis. | Month 3-18 | 
| Number of Participants With DNV Resistance Status-Clonal Sequencing | Clonal sequencing was used for determination of loss of resistance status. Resistance status was reported as either with loss of DNV resistance or without loss of DNV resistance. Category 1-Number of participants with loss of resistance in NV22688. A total of 64 participants with loss of resistance in NV22688 were included in this analysis. Category 2-Number of participants with no loss of resistance in NV22688. A total of 35 participants with no loss of resistance in NV22688 were included in this analysis. Category 3-Number of participants with loss of resistance in donor study. A total of 26 participants who had no DNV resistance at the end of donor study were analyzed by clonal sequencing in NV22688. Three participants from donor studies WV21913, NP28266 and NP27946, respectively were not analyzed by clonal sequencing in NV22688 as loss of resistance mutations was demonstrated by clonal sequencing in donor study. | Month 3-18 | 
| Number of Participants With Boceprevir (BOC) or Telaprevir (TVR) Resistance Status-Population Sequencing | Population sequencing was used for determination of loss of resistance status. Resistance status was reported as either with loss of BOC or TVR resistance or without loss of BOC or TVR resistance. Category 1-Number of participants with loss of resistance in NV22688. A total of 6 participants with resistance at the end of donor study by population sequencing were included in this analysis. Category 2-Number of participants with no loss resistance in NV22688. One participant with resistance at the end of donor study by population sequencing was included in this analysis. Category 3-Number of participants with loss of resistance in donor study. A total of 2 participants with no BOC or TVR resistance at the end of donor study by population sequencing enrolled in NV22688 were included in this analysis. | Month 3-18 | 
| Number of Participants With BOC or TVR Resistance Status-Clonal Sequencing | Clonal sequencing was used for determination of loss of resistance status. Resistance status was reported as either with loss of BOC or TVR resistance or without loss of BOC or TVR resistance. Category 1-Number of participants with loss of resistance in NV22688. A total of 3 participants with loss of resistance in NV22688 were included in this analysis. Category 2-Number of participants with no loss of resistance in NV22688. A total of 3 participants with no loss of resistance in NV22688 were included in this analysis. Category 3-Number of participants with loss of resistance in donor study. A total of 2 participants who had no resistance at the end of donor study were analyzed by clonal sequencing in NV22688. | Month 3-18 | 
| Number of Participants With Setrobuvir (STV) Resistance Status-Population Sequencing | Population sequencing was used for determination of loss of resistance status. Resistance status was reported as either with loss of STV resistance or without loss of STV resistance. Category 1-Number of participants with loss of resistance in NV22688. A total of 5 participants with resistance at the end of donor study by population sequencing were included in this analysis. Category 2-Number of participants with no loss resistance in NV22688. A total of 3 participants with resistance at the end of donor study by population sequencing were included in this analysis. Category 3-Number of participants with loss of resistance in donor study. A total of 3 participants with no STV resistance at the end of donor study by population sequencing enrolled in NV22688 were included in this analysis. | Month 3-18 | 
| Number of Participants With STV Resistance Status-Clonal Sequencing | Clonal sequencing was used for determination of loss of resistance status. Resistance status was reported as either with loss of STV resistance or without loss of STV resistance. Category 1-Number of participants with loss of resistance in NV22688. One participant with loss of resistance in NV22688 was included in this analysis. Category 2-Number of participants with no loss of resistance in NV22688. A total of 4 participants with no loss of resistance in NV22688 were included in this analysis. Category 3-Number of participants with loss of resistance in donor study. One participant with loss of resistance, analyzed by clonal sequencing in NV22688. Category 4-Number of participants with loss of resistance in donor study. Two participants with no loss of resistance, analyzed by clonal sequencing in NV22688. | Month 3-18 | 
| Number of Participants Who Had Received Mericitabine (MCB)-Based Regimen and Enrolled in NV22688 | Population sequencing was used for determination of loss of resistance status. Results are reported as per donor protocol. | Month 18 |