Hepatitis C
Conditions
Keywords
Hepatitis C, Hepatitis, TMC435, Liver disease, Virus Infection
Brief summary
The purpose of this study is to investigate durability of SVR in chronic HCV patients who achieved SVR in the previous study with TMC435-containing regimen and time for resistance associated mutations to return to baseline in chronic HCV patients who did not achieve SVR in the previous study with TMC435-containing regimen.
Detailed description
This is a 3-year follow-up study in patients who completed the last post-therapy follow-up visit of the previous Phase IIb \[NCT00882908, NCT00980330\] or Phase III \[NCT01289782, NCT01290679, NCT01281839\] study in which they received TMC435, in combination with pegylated interferon and ribavirin, for the treatment of hepatitis C infection. The entire study duration for each patients will be approximately 36 months. The medical follow-up of the patients will be performed according to the local standard of care. This study will evaluate the levels of hepatitis C virus in the blood circulation, as well as safety and alpha-fetoprotein testing and the change in sequence of HCV NS3/4A region over time in patients with confirmed detectable HCV RNA at last post-therapy follow-up visit of the previous TMC435 study. In this study the development of liver disease progression will also be assessed. No medication will be administered in this study.
Interventions
DRUGNo treatment
No treatment was given to patients during this study as this is a follow-up study of previous Phase IIb or Phase III in which they received a TMC435-containing regimen.
Sponsors
Janssen R&D Ireland
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have previously participated in a Phase IIb or Phase III study * Must have received at least one dose of TMC435 in that study * Has completed the last post-therapy follow-up visit of the previous (LPVPS) study
Exclusion criteria
* Must be currently enrolled or plan to enroll in another study with an investigational drug or invasive investigational medical device * Have received antiviral or immunomodulating treatment, including therapeutic vaccines, for hepatitis C virus (HCV) between LPVPS and the screening visit of present study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Maintaining SVR at the Last Available Visit | Last Available Visit (Month 36 for subjects completing the study) | The SVR rate is the proportion (%) of participants with HCV RNA less than (\<) 25 International Units/milliliter (IU/mL). |
| Overall Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA at the Last Visit of the Previous Study | Baseline and Month 36 | Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study. |
| Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (With Q80K at Baseline) at the Last Visit of the Previous Study | Baseline and Month 36 | Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study. |
| Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (Without Q80K at Baseline) at the Last Visit of the Previous Study | Baseline and Month 36 | Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Late Viral Relapse | End of study (at month 36) | Relapse at any time after the LPVPS until the last individual visit of this study. All participants maintained SVR until the last available visit. No late viral relapse was therefore observed. |
| Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | End of study (at month 36) | — |
Countries
Belgium, Canada, France, Germany, Poland, Russia, United States
Participant flow
Pre-assignment details
In total 250 participants were screened and among those 249 were enrolled into the study (200 participants with SVR and 49 participants with no SVR).
Participants by arm
| Arm | Count |
|---|---|
| SVR at Last Post-Therapy Follow-up Visit of Previous Study Participants with sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb \[NCT00882908, NCT00980330\] or Phase III \[NCT01289782, NCT01290679, NCT01281839\] study. | 200 |
| No SVR at Last Post-Therapy Follow-up Visit of Previous Study Participants with no sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb \[NCT00882908, NCT00980330\] or Phase III \[NCT01289782, NCT01290679, NCT01281839\] study. | 49 |
| Total | 249 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 3 | 0 |
| Overall Study | Lost to Follow-up | 10 | 1 |
| Overall Study | Subject Ineligible To Continue The Trial | 0 | 19 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | SVR at Last Post-Therapy Follow-up Visit of Previous Study | No SVR at Last Post-Therapy Follow-up Visit of Previous Study | Total |
|---|---|---|---|
| Age, Continuous | 52 years | 56 years | 53 years |
| Sex: Female, Male Female | 78 Participants | 17 Participants | 95 Participants |
| Sex: Female, Male Male | 122 Participants | 32 Participants | 154 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 200 | 1 / 49 | 5 / 249 |
| serious Total, serious adverse events | 10 / 200 | 0 / 49 | 10 / 249 |
Outcome results
Primary
Overall Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA at the Last Visit of the Previous Study
Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.
Time frame: Baseline and Month 36
Population: N signifies number of participants with no SVR at LPVPS and with available sequence data. n defines the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Overall Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA at the Last Visit of the Previous Study | NEM Return to Baseline at EOS (n=5) | 0.0 Percentage of participants |
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Overall Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA at the Last Visit of the Previous Study | NEM Change to New Profile at EOS (n=5) | 0.0 Percentage of participants |
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Overall Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA at the Last Visit of the Previous Study | AEM Return to Baseline at EOS (n=43) | 86.0 Percentage of participants |
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Overall Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA at the Last Visit of the Previous Study | AEM Change to New Profile at EOS (n=43) | 7.0 Percentage of participants |
Primary
Percentage of Participants Maintaining SVR at the Last Available Visit
The SVR rate is the proportion (%) of participants with HCV RNA less than (\<) 25 International Units/milliliter (IU/mL).
Time frame: Last Available Visit (Month 36 for subjects completing the study)
Population: All participants with SVR at LPVPS were included in the population analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Percentage of Participants Maintaining SVR at the Last Available Visit | 100 Percentage of participants |
Primary
Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (Without Q80K at Baseline) at the Last Visit of the Previous Study
Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.
Time frame: Baseline and Month 36
Population: N signifies number of particpants with no SVR at LPVPS and with available sequence data. n defines the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (Without Q80K at Baseline) at the Last Visit of the Previous Study | NEM Return to Baseline at EOS (n=4) | 0.0 Percentage of participnats |
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (Without Q80K at Baseline) at the Last Visit of the Previous Study | AEM Change to New Profile at EOS (n=34) | 8.8 Percentage of participnats |
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (Without Q80K at Baseline) at the Last Visit of the Previous Study | NEM Change to New Profile at EOS (n=4) | 0.0 Percentage of participnats |
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (Without Q80K at Baseline) at the Last Visit of the Previous Study | AEM Return to Baseline at EOS (n=34) | 85.3 Percentage of participnats |
Primary
Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (With Q80K at Baseline) at the Last Visit of the Previous Study
Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.
Time frame: Baseline and Month 36
Population: N signifies number of particpants with no SVR at LPVPS and with available sequence data. n defines the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (With Q80K at Baseline) at the Last Visit of the Previous Study | AEM Change to New Profile at EOS (n=9) | 0.0 Percentage of participants |
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (With Q80K at Baseline) at the Last Visit of the Previous Study | NEM Return to Baseline at EOS (n=1) | 0.0 Percentage of participants |
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (With Q80K at Baseline) at the Last Visit of the Previous Study | NEM Change to New Profile at EOS (n=1) | 0.0 Percentage of participants |
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (With Q80K at Baseline) at the Last Visit of the Previous Study | AEM Return to Baseline at EOS (n=9) | 88.9 Percentage of participants |
Secondary
Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
Time frame: End of study (at month 36)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | Adverse Events (AE) | 4 Participants |
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | Serious Adverse Events (SAE) | 10 Participants |
| No SVR at Last Post-Therapy Follow-up Visit of Previous Study | Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | Adverse Events (AE) | 1 Participants |
| No SVR at Last Post-Therapy Follow-up Visit of Previous Study | Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | Serious Adverse Events (SAE) | 0 Participants |
Secondary
Percentage of Participants With Late Viral Relapse
Relapse at any time after the LPVPS until the last individual visit of this study. All participants maintained SVR until the last available visit. No late viral relapse was therefore observed.
Time frame: End of study (at month 36)
Population: Late viral relapse was evaluated in all enrolled participants with SVR at LPVPS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SVR at Last Post-Therapy Follow-up Visit of Previous Study | Percentage of Participants With Late Viral Relapse | 0 percentage of participants |