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

This study has been terminated.
(This study was terminated due to the decrease in percentage of participants.)
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01168856
First received: July 15, 2010
Last updated: February 12, 2016
Last verified: February 2016
  Purpose
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.

Condition
Hepatitis C, Chronic

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With the Detectable HCV Ribonucleic Acid (RNA) Results in Resistance Monitoring Arm at Month 3 [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
    Serum HCV RNA concentration was determined using the Roche COBAS TaqMan HCV Test (Detection limit = 15 International Units per milliliter [IU/mL]).

  • Percentage of Participants With the Detectable HCV RNA Results in Resistance Monitoring Arm at Month 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 9 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 18 ] [ Designated as safety issue: No ]
    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 3 [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 9 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 18 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
    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 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator.

  • Systolic Blood Pressure in Resistance Monitoring Arm at Month 9 [ Time Frame: Month 9 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 18 ] [ Designated as safety issue: No ]
    Any abnormalities in systolic blood pressure were reported at the discretion of principal investigator.

  • Mean Diastolic Blood Pressure in Resistance Monitoring Arm at Month 3 [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
    Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator.

  • Mean Diastolic Blood Pressure in Resistance Monitoring Arm at Month 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 9 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 18 ] [ Designated as safety issue: No ]
    Any abnormalities in diastolic blood pressure were reported at the discretion of principal investigator.

  • Mean Pulse Rate in Resistance Monitoring Arm at Month 3 [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
    Any abnormalities in pulse rate were reported at the discretion of principal investigator.

  • Mean Pulse Rate in Resistance Monitoring Arm at Month 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    Any abnormalities in pulse rate were reported at the discretion of principal investigator.

  • Mean Pulse Rate in Resistance Monitoring Arm at Month 9 [ Time Frame: Month 9 ] [ Designated as safety issue: No ]
    Any abnormalities in pulse rate were reported at the discretion of principal investigator.

  • Mean Pulse Rate in Resistance Monitoring Arm at Month 12 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Any abnormalities in pulse rate were reported at the discretion of principal investigator.

  • Mean Pulse Rate in Resistance Monitoring Arm at Month 18 [ Time Frame: Month 18 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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 24 [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
    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 36 [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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 24 [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    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 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    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 12 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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 24 [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    Any abnormalities in pulse rate were reported at the discretion of principal investigator.

  • Mean Pulse Rate in SVR Durability Monitoring Arm at Month 12 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Any abnormalities in pulse rate were reported at the discretion of principal investigator.

  • Mean Pulse Rate in SVR Durability Monitoring Arm at Month 24 [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
    Any abnormalities in pulse rate were reported at the discretion of principal investigator.

  • Mean Pulse Rate in SVR Durability Monitoring Arm at Month 36 [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    Any abnormalities in pulse rate were reported at the discretion of principal investigator.

  • Number of Participants With Danoprevir (DNV) Resistance Status-Population Sequencing [ Time Frame: Month 3-18 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Month 3-18 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Month 3-18 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Month 3-18 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Month 3-18 ] [ Designated as safety issue: No ]

    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.


  • Number of Participants With STV Resistance Status-Clonal Sequencing [ Time Frame: Month 3-18 ] [ Designated as safety issue: No ]

    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.


  • Number of Participants Who Had Received Mericitabine (MCB)-Based Regimen and Enrolled in NV22688 [ Time Frame: Month 18 ] [ Designated as safety issue: No ]
    Population sequencing was used for determination of loss of resistance status. Results are reported as per donor protocol.


Biospecimen Retention:   None Retained
Serum specimens collected from patients with partial viral response or viral load rebound of viral response to monitor for resistance mutations in viral RNA

Enrollment: 734
Study Start Date: September 2010
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Chronic hepatitis C patients having received direct acting antiviral treatment in donor protocol
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01168856

  Show 126 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01168856     History of Changes
Other Study ID Numbers: NV22688  2009-016560-36 
Study First Received: July 15, 2010
Results First Received: December 30, 2015
Last Updated: February 12, 2016
Health Authority: France: AFSSAPS

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 27, 2016