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

Hepatitis C, Chronic Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01168856
• Other study ID #: NV22688
• Secondary ID: 2009-016560-36
• Status: Terminated
• Phase: N/A
• First received: July 15, 2010
• Last updated: February 12, 2016
• Start date: September 2010
• Est. completion date: April 2015

Study information

• Verified date: February 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: AFSSAPS
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 734
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  Canada,  France,  Germany,  Italy,  Mexico,  New Zealand,  Poland,  Puerto Rico,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No