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

Terminated

• Conditions: Hepatitis C, Chronic

• Registration Number: NCT01168856
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-07-15
• Study First Submitted QC: 2010-07-22
• Study First Posted: 2010-07-23
• Study Start: 2010-09
• Primary Completion: 2015-04
• Study Completion: 2015-04
• Results First Submitted: 2015-12-30
• Status Verified: 2016-02
• Results First Submitted QC: 2016-02-12
• Last Update Submitted: 2016-02-12
• Results First Posted: 2016-03-11
• Last Update Posted: 2016-03-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 734

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With the Detectable HCV Ribonucleic Acid (RNA) Results in Resistance Monitoring Arm at Month 3	Month 3	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 International Units per milliliter \[IU/mL\]).
HCV RNA Levels in Resistance Monitoring Arm at Month 3	Month 3	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
HCV RNA Levels in Resistance Monitoring Arm at Month 6	Month 6	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Percentage of Participants With the Detectable HCV RNA Results in Resistance Monitoring Arm at Month 6	Month 6	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Percentage of Participants With the Detectable HCV RNA Results in Resistance Monitoring Arm at Month 9	Month 9	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
HCV RNA Levels in Resistance Monitoring Arm at Month 18	Month 18	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Percentage of Participants With the Detectable HCV RNA Results in Resistance Monitoring Arm at Month 12	Month 12	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Percentage of Participants With the Detectable HCV RNA Results in Resistance Monitoring Arm at Month 18	Month 18	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
HCV RNA Levels in Resistance Monitoring Arm at Month 9	Month 9	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
HCV RNA Levels in Resistance Monitoring Arm at Month 12	Month 12	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Mean Systolic Blood Pressure in Resistance Monitoring Arm at Month 3	Month 3	Any abnormalities in systolic blood pressure (units: millimeters of Mercury \[Hg\] \[mmHg\]) were reported at the discretion of principal investigator.
Systolic Blood Pressure in Resistance Monitoring Arm at Month 9	Month 9	Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator.
Mean Systolic Blood Pressure in Resistance Monitoring Arm at Month 12	Month 12	Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator.
Mean Systolic Blood Pressure in Resistance Monitoring Arm at Month 18	Month 18	Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator.
Systolic Blood Pressure in Resistance Monitoring Arm at Month 6	Month 6	Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator.
Mean Diastolic Blood Pressure in Resistance Monitoring Arm at Month 6	Month 6	Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator.
Mean Diastolic Blood Pressure in Resistance Monitoring Arm at Month 3	Month 3	Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator.
Mean Diastolic Blood Pressure in Resistance Monitoring Arm at Month 9	Month 9	Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator.
Mean Diastolic Blood Pressure in Resistance Monitoring Arm at Month 12	Month 12	Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator.
Mean Diastolic Blood Pressure in Resistance Monitoring Arm at Month 18	Month 18	Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator.
Mean Pulse Rate in Resistance Monitoring Arm at Month 3	Month 3	Any abnormalities in pulse rate were reported at the discretion of principal investigator.
Mean Pulse Rate in Resistance Monitoring Arm at Month 6	Month 6	Any abnormalities in pulse rate were reported at the discretion of principal investigator.
Mean Pulse Rate in Resistance Monitoring Arm at Month 9	Month 9	Any abnormalities in pulse rate were reported at the discretion of principal investigator.
Mean Pulse Rate in Resistance Monitoring Arm at Month 12	Month 12	Any abnormalities in pulse rate were reported at the discretion of principal investigator.
Mean Pulse Rate in Resistance Monitoring Arm at Month 18	Month 18	Any abnormalities in pulse rate were reported at the discretion of principal investigator.
Percentage of Participants Who Received Anti-HCV Medications in Resistance Monitoring Arm	Up to 18 months	Percentage of participants who received any anti-HCV medication during the monitoring period was reported.
Percentage of Participants With the Detectable HCV RNA Results in SVR Durability Monitoring Arm at Month 6	Month 6	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Percentage of Participants With the Detectable HCV RNA Results in SVR Durability Monitoring Arm at Month 12	Month 12	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Percentage of Participants With the Detectable HCV RNA Results in SVR Durability Monitoring Arm at Month 24	Month 24	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Percentage of Participants With the Detectable HCV RNA Results in SVR Durability Monitoring Arm at Month 36	Month 36	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Mean HCV RNA Levels in SVR Durability Monitoring Arm at Month 6	Month 6	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Mean HCV RNA Levels in SVR Durability Monitoring Arm at Month 12	Month 12	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Mean Diastolic Blood Pressure in SVR Durability Monitoring Arm at Month 24	Month 24	Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator.
Mean Pulse Rate in SVR Durability Monitoring Arm at Month 6	Month 6	Any abnormalities in pulse rate were reported at the discretion of principal investigator.
Number of Participants With STV Resistance Status-Clonal Sequencing	Month 3-18	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.
Mean HCV RNA Levels in SVR Durability Monitoring Arm at Month 24	Month 24	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Mean Systolic Blood Pressure in SVR Durability Monitoring Arm at Month 24	Month 24	Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator.
Mean Diastolic Blood Pressure in SVR Durability Monitoring Arm at Month 12	Month 12	Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator.
Mean Diastolic Blood Pressure in SVR Durability Monitoring Arm at Month 36	Month 36	Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator.
Mean HCV RNA Levels in SVR Durability Monitoring Arm at Month 36	Month 36	Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 IU/mL).
Mean Systolic Blood Pressure in SVR Durability Monitoring Arm at Month 6	Month 6	Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator.
Mean Systolic Blood Pressure in SVR Durability Monitoring Arm at Month 12	Month 12	Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator.
Mean Systolic Blood Pressure in SVR Durability Monitoring Arm at Month 36	Month 36	Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator.
Mean Pulse Rate in SVR Durability Monitoring Arm at Month 12	Month 12	Any abnormalities in pulse rate were reported at the discretion of principal investigator.
Number of Participants Who Had Received Mericitabine (MCB)-Based Regimen and Enrolled in NV22688	Month 18	Population sequencing was used for determination of loss of resistance status. Results are reported as per donor protocol.
Mean Diastolic Blood Pressure in SVR Durability Monitoring Arm at Month 6	Month 6	Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator.
Mean Pulse Rate in SVR Durability Monitoring Arm at Month 24	Month 24	Any abnormalities in pulse rate were reported at the discretion of principal investigator.
Mean Pulse Rate in SVR Durability Monitoring Arm at Month 36	Month 36	Any abnormalities in pulse rate were reported at the discretion of principal investigator.
Number of Participants With Danoprevir (DNV) Resistance Status-Population Sequencing	Month 3-18	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.
Number of Participants With DNV Resistance Status-Clonal Sequencing	Month 3-18	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.
Number of Participants With Boceprevir (BOC) or Telaprevir (TVR) Resistance Status-Population Sequencing	Month 3-18	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.
Number of Participants With BOC or TVR Resistance Status-Clonal Sequencing	Month 3-18	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.
Number of Participants With Setrobuvir (STV) Resistance Status-Population Sequencing	Month 3-18	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.