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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Hepatitis C, Chronic

• Study Type: Observational
• Enrollment (Actual): 734

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
    • Kingswood, New South Wales, Australia, 2747
    • Sydney, New South Wales, Australia, 2050
    • Westmead, New South Wales, Australia, 2145
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
    • Herston, Queensland, Australia, 4029
    • Woolloongabba, Queensland, Australia, 4102
  • South Australia
    • Adelaide, South Australia, Australia, 5000
  • Victoria
    • Melbourne, Victoria, Australia, 3181
    • Melbourne, Victoria, Australia, 3186
• Austria
  • Wien, Austria, 1080
• Brazil
  • BA
    • Salvador, BA, Brazil, 40210-341
  • RS
    • Porto Alegre, RS, Brazil, 90035-003
  • SP
    • Ribeirao Preto, SP, Brazil, 14049-900
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
    • Edmonton, Alberta, Canada, T6G 2B7
    • Edmonton, Alberta, Canada, T6L5X8
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
    • Vancouver, British Columbia, Canada, V5Z 1H2
    • Vancouver, British Columbia, Canada, V6Z 2K5
    • Vancouver, British Columbia, Canada, V6Z 2C7
    • Victoria, British Columbia, Canada, V8V 3P9
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
  • Ontario
    • London, Ontario, Canada, N6A 5A5
    • Ottawa, Ontario, Canada, K1H 8L6
    • Toronto, Ontario, Canada, M5T 2S8
    • Toronto, Ontario, Canada, M5G 1L7
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
• France
  • Clichy, France, 92118
  • Creteil, France, 94010
  • Lille, France, 59037
  • Marseille, France, 13285
  • Montpellier, France, 34295
  • Montpellier, France, 34094
  • Nice, France, 06202
  • Paris, France, 75651
  • Paris, France, 75679
  • Pessac, France, 33604
  • Rennes, France, 35033
  • Toulouse, France, 31059
  • Vandoeuvre-les-nancy, France, 54511
• Germany
  • Berlin, Germany, 13353
  • Berlin, Germany, 10969
  • Frankfurt Am Main, Germany, 60590
  • Hamburg, Germany, 20099
  • Hannover, Germany, 30625
  • Muenchen, Germany, 81377
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
  • Lombardia
    • Milano, Lombardia, Italy, 20162
    • Milano, Lombardia, Italy, 20121
    • Pavia, Lombardia, Italy, 27100
  • Piemonte
    • Torino, Piemonte, Italy, 10126
  • Puglia
    • Bari, Puglia, Italy, 70124
  • Toscana
    • Pisa, Toscana, Italy, 56124
• Mexico
  • Guadalajara, Mexico, 44650
  • Guadalajara, Mexico, 44280
  • Monterrey, Mexico, 64710
• New Zealand
  • Christchurch, New Zealand, 8011
  • Dunedin, New Zealand, 9016
  • Grafton, New Zealand, 1010
• Poland
  • Bydgoszcz, Poland, 85-030
  • Chorzow, Poland, 41-500
  • Lodz, Poland, 91-357
  • Myslowice, Poland, 41-400
  • Warszawa, Poland, 01-201
  • Warszawa, Poland, 02-507
  • Wrocław, Poland, 50-349
  • Łodz, Poland, 91-347
• Puerto Rico
  • San Juan, Puerto Rico, 00927
• Slovakia
  • Bratislava, Slovakia, 831 01
• Spain
  • Barcelona, Spain, 08003
  • Barcelona, Spain, 08035
  • Madrid, Spain, 28034
  • Madrid, Spain, 28222
  • Madrid, Spain, 28029
  • Pontevedra, Spain, 36071
  • Sevilla, Spain, 41014
  • Valencia, Spain, 46014
  • Barcelona
    • Badalona, Barcelona, Spain, 08915
  • Cantabria
    • Santander, Cantabria, Spain, 39008
  • Islas Baleares
    • Palma de Mallorca, Islas Baleares, Spain, 07010
  • La Coruña
    • La Coruna, La Coruña, Spain, 15006
  • Tenerife
    • La Laguna, Tenerife, Spain, 38320
• United Kingdom
  • Dorset, United Kingdom, BH7 7DW
  • Dundee, United Kingdom, DD1 9SY
  • London, United Kingdom, SE5 9RS
  • London, United Kingdom, W2 1NY
  • London, United Kingdom, E1 1BB
  • London, United Kingdom, SW17 0QT
  • Manchester, United Kingdom, M8 5RB
  • Nottingham, United Kingdom, NG7 2UH
• United States
  • California
    • La Jolla, California, United States, 92037-1030
    • Long Beach, California, United States, 90822
    • Sacramento, California, United States, 95817
    • Sacramento, California, United States, 95825
    • San Diego, California, United States, 92103-8465
    • San Francisco, California, United States, 94115
  • Colorado
    • Aurora, Colorado, United States, 80045
    • Englewood, Colorado, United States, 80113
  • Florida
    • Bradenton, Florida, United States, 34209
  • Georgia
    • Atlanta, Georgia, United States, 30309
    • Decatur, Georgia, United States, 30033
    • Marietta, Georgia, United States, 30060
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
  • Illinois
    • Chicago, Illinois, United States, 60637
  • Indiana
    • Indianapolis, Indiana, United States, 46202
  • Kansas
    • Kansas City, Kansas, United States, 66160-7222
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
  • Michigan
    • Detroit, Michigan, United States, 48202
  • Missouri
    • Kansas City, Missouri, United States, 64131
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
    • Newark, New Jersey, United States, 07102
  • New York
    • Manhasset, New York, United States, 11030
    • New York, New York, United States, 10021
    • New York, New York, United States, 10003
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
  • Tennessee
    • Nashville, Tennessee, United States, 37211
  • Texas
    • Dallas, Texas, United States, 75246
    • Houston, Texas, United States, 77030
    • San Antonio, Texas, United States, 78212
    • San Antonio, Texas, United States, 78234
  • Virginia
    • Newport News, Virginia, United States, 23602
    • Richmond, Virginia, United States, 23249
  • Washington
    • Vancouver, Washington, United States, 98604

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Chronic hepatitis C patients having received direct acting antiviral treatment in donor protocol

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Cohort

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: July 15, 2010
• First Submitted That Met QC Criteria: July 22, 2010
• First Posted (Estimate): July 23, 2010

Study Record Updates

• Last Update Posted (Estimate): March 11, 2016
• Last Update Submitted That Met QC Criteria: February 12, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: NV22688; 2009-016560-36 (EudraCT Number)