Hepatitis C
Conditions
Keywords
Genotype 1
Brief summary
This study is being conducted to learn more about the safety and effect of telaprevir in combination with peginterferon alfa-2a (PEG-IFN) and ribavirin (RBV) in participants with hepatitis C who have never been treated for their hepatitis C virus (HCV). The study is designed to look at the relative benefits of 24 or 48 weeks of total treatment in people who respond quickly to a telaprevir-based treatment.
Interventions
DRUGtelaprevir
750 mg every 8 hours (q8h) for 12 weeks
DRUGribavirin
1000 - 1200 mg/day based on body weight for either 24 or 48 weeks
BIOLOGICALpeginterferon alfa-2a
180 mcg/week for either 24 or 48 weeks
Sponsors
Tibotec Pharmaceutical Limited
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Has not received any previous treatment with any approved or investigational drug or drug regimen for the treatment of hepatitis C * Male and female subjects, 18 to 70 years of age, inclusive * Genotype 1, chronic hepatitis C with detectable HCV RNA. * Screening laboratory values, tests, and physical exam within acceptable ranges * Able and willing to follow contraception requirements * Able to read and understand, and willing to sign the informed consent form and abide by the study restrictions.
Exclusion criteria
* Subject has any contraindications to Pegasys® or Copegus® therapy * Evidence of hepatic decompensation in cirrhotic subjects * History of organ transplant * History of, or any current medical condition which could impact the safety of the subject in participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Randomized Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable HCV RNA 24 Weeks After Last Dose of Study Treatment (SVR24) | 24 weeks after the last planned dose of study treatment | SVR24planned was used to measure the primary outcome. SVR24 planned is defined as undetectable HCV RNA levels at the end of treatment (EOT) visit and at 24 weeks after the last planned dose of study treatment without any confirmed detectable HCV RNA levels in between those visits. All plasma HCV RNA levels were assessed using the Roche TaqMan HCV RNA assay (Version 2.0, lower limit of quantification \[LLOQ\] of 25 IU/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving eRVR (Extended RVR), Demonstrated by Achieving Undetectable HCV RNA at Week 4 and at Week 12 | Week 4 and Week 12 | Extended rapid viral response is defined undetectable HCV RNA levels at Week 4 and Week 12 (on treatment). |
| Proportion of Randomized Subjects Who Have Undetectable HCV RNA 12 Weeks After Last Dose of Study Treatment | 12 weeks after last dose of study treatment | SVR12 is defined as undetectable HCV RNA levels 12 weeks after the last planned dose of study treatment. |
| Proportion of Subjects Who Have Undetectable HCV RNA at the EOT (Week 24 or Week 48 Respectively) | Week 24 or Week 48 | — |
| Proportion of Subjects Who Have Undetectable HCV RNA at Week 72 | 72 weeks after the last planned dose of study treatment | SVR at Week 72 is defined as achieved SVR24planned and undetectable HCV RNA at Week 72 without any confirmed detectable HCV RNA levels in between those visits. |
| Proportion of Enrolled Subjects Who Relapse | From EOT to Week 48 or Week 72 | Proportion of enrolled subjects who relapsed was defined as the number of subjects who had undetectable HCV RNA at the EOT, and became HCV RNA detectable during antiviral follow-up. |
| Safety and Tolerability as Assessed by Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Week 72 | — |
| Proportion of Randomized Subjects Who Relapse | From EOT to Week 48 or Week 72 | Proportion of randomized subjects who relapsed was defined as the number of subjects who completed treatment, had undetectable HCV RNA at end of treatment (EOT; Week 24 or Week 48 respectively), and became HCV RNA detectable during antiviral follow-up (24 weeks after EOT). |
Countries
Belgium, Netherlands, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| T12PR24 (eRVR+) Telaprevir + Peg-IFN-alfa-2a + RBV for 12 weeks, followed by 12 weeks of Peg-IFN-alfa-2a and RBV; subjects achieved an extended rapid viral response (eRVR+) and were randomized to this group | 162 |
| T12PR48 (eRVR+) Telaprevir + Peg-IFN-alfa-2a + RBV for 12 weeks, followed by 36 weeks of Peg-IFN-alfa-2a and RBV; subjects achieved an extended rapid viral response (eRVR+) and were randomized to this group | 160 |
| T12PR48 (eRVR-) Telaprevir + Peg-IFN-alfa-2a + RBV for 12 weeks, followed by 36 weeks of Peg-IFN-alfa-2a and RBV; subjects did not achieve an extended rapid viral response (eRVR-) and were assigned to this group | 118 |
| Other Subjects who received at least 1 dose of study drug, but prematurely discontinued treatment before Week 20 were not randomized or assigned to a treatment regimen. | 100 |
| Total | 540 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 20 | 12 | 62 |
| Overall Study | Lack of Efficacy | 0 | 6 | 18 | 12 |
| Overall Study | Lost to Follow-up | 0 | 2 | 2 | 5 |
| Overall Study | Non-Compliant With study Drug | 0 | 0 | 0 | 1 |
| Overall Study | Other Reasons | 0 | 1 | 0 | 5 |
| Overall Study | Refused Further Treatment | 0 | 11 | 5 | 8 |
| Overall Study | Required Prohibited Medication | 0 | 0 | 1 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 4 |
Baseline characteristics
| Characteristic | T12PR24 (eRVR+) | T12PR48 (eRVR+) | T12PR48 (eRVR-) | Other | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 0 Participants | 1 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 158 Participants | 157 Participants | 118 Participants | 99 Participants | 532 Participants |
| Age, Continuous | 48.6 years STANDARD_DEVIATION 8.9 | 48.3 years STANDARD_DEVIATION 9.9 | 49.5 years STANDARD_DEVIATION 8.7 | 51.6 years STANDARD_DEVIATION 8.4 | 49.3 years STANDARD_DEVIATION 9.2 |
| Region of Enrollment Europe | 8 participants | 9 participants | 12 participants | 2 participants | 31 participants |
| Region of Enrollment North America | 154 participants | 151 participants | 106 participants | 98 participants | 509 participants |
| Sex: Female, Male Female | 58 Participants | 63 Participants | 48 Participants | 46 Participants | 215 Participants |
| Sex: Female, Male Male | 104 Participants | 97 Participants | 70 Participants | 54 Participants | 325 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 161 / 162 | 160 / 160 | 117 / 118 | 99 / 100 |
| serious Total, serious adverse events | 4 / 162 | 16 / 160 | 7 / 118 | 22 / 100 |
Outcome results
Primary
Proportion of Randomized Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable HCV RNA 24 Weeks After Last Dose of Study Treatment (SVR24)
SVR24planned was used to measure the primary outcome. SVR24 planned is defined as undetectable HCV RNA levels at the end of treatment (EOT) visit and at 24 weeks after the last planned dose of study treatment without any confirmed detectable HCV RNA levels in between those visits. All plasma HCV RNA levels were assessed using the Roche TaqMan HCV RNA assay (Version 2.0, lower limit of quantification \[LLOQ\] of 25 IU/mL).
Time frame: 24 weeks after the last planned dose of study treatment
Population: The population analyzed included all subjects in the Full Analysis (FA) Set. All subjects in the FA Set received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T12PR24 (eRVR+) | Proportion of Randomized Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable HCV RNA 24 Weeks After Last Dose of Study Treatment (SVR24) | SVR24 (Statistical Analysis 1) | 149 participants |
| T12PR24 (eRVR+) | Proportion of Randomized Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable HCV RNA 24 Weeks After Last Dose of Study Treatment (SVR24) | SVR24 (Statistical Analysis 2) | 149 participants |
| T12PR48 (eRVR+) | Proportion of Randomized Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable HCV RNA 24 Weeks After Last Dose of Study Treatment (SVR24) | SVR24 (Statistical Analysis 2) | 144 participants |
| T12PR48 (eRVR+) | Proportion of Randomized Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable HCV RNA 24 Weeks After Last Dose of Study Treatment (SVR24) | SVR24 (Statistical Analysis 1) | 140 participants |
| T12PR48 (eRVR-) | Proportion of Randomized Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable HCV RNA 24 Weeks After Last Dose of Study Treatment (SVR24) | SVR24 (Statistical Analysis 1) | 76 participants |
| T12PR48 (eRVR-) | Proportion of Randomized Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable HCV RNA 24 Weeks After Last Dose of Study Treatment (SVR24) | SVR24 (Statistical Analysis 2) | 78 participants |
| Other | Proportion of Randomized Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable HCV RNA 24 Weeks After Last Dose of Study Treatment (SVR24) | SVR24 (Statistical Analysis 1) | 23 participants |
| Other | Proportion of Randomized Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable HCV RNA 24 Weeks After Last Dose of Study Treatment (SVR24) | SVR24 (Statistical Analysis 2) | 27 participants |
Comparison: Primary efficacy analysis was based on CI estimates (using the normal approximation, confidence limits were constructed for the difference in proportions) to rule out the inferiority of the T12/PR24/eRVR+ treatment regimen relative to the T12/PR48/eRVR+ treatment regimen. SVR24 was defined as undetectable HCV RNA at end of treatment through 24 weeks after the last planned dose.95% CI: [-2.1, 11.1]
Comparison: SVR24 was defined as below the limit of quantitation at 24 weeks after the planned end of treatment. For subjects who had missing data at week 24 after the planned end of treatment, the week 12 data or the last follow-up time point after week 12 was carried forward for determining SVR24.95% CI: [-4.3, 8.2]
Secondary
Proportion of Enrolled Subjects Who Relapse
Proportion of enrolled subjects who relapsed was defined as the number of subjects who had undetectable HCV RNA at the EOT, and became HCV RNA detectable during antiviral follow-up.
Time frame: From EOT to Week 48 or Week 72
Population: The population analyzed included all subjects in the Full Analysis (FA) Set. All subjects in the FA Set received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T12PR24 (eRVR+) | Proportion of Enrolled Subjects Who Relapse | 9 participants |
| T12PR48 (eRVR+) | Proportion of Enrolled Subjects Who Relapse | 4 participants |
| T12PR48 (eRVR-) | Proportion of Enrolled Subjects Who Relapse | 11 participants |
| Other | Proportion of Enrolled Subjects Who Relapse | 13 participants |
Secondary
Proportion of Randomized Subjects Who Have Undetectable HCV RNA 12 Weeks After Last Dose of Study Treatment
SVR12 is defined as undetectable HCV RNA levels 12 weeks after the last planned dose of study treatment.
Time frame: 12 weeks after last dose of study treatment
Population: The population analyzed included all subjects in the Full Analysis (FA) Set. All subjects in the FA Set received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T12PR24 (eRVR+) | Proportion of Randomized Subjects Who Have Undetectable HCV RNA 12 Weeks After Last Dose of Study Treatment | 151 participants |
| T12PR48 (eRVR+) | Proportion of Randomized Subjects Who Have Undetectable HCV RNA 12 Weeks After Last Dose of Study Treatment | 144 participants |
| T12PR48 (eRVR-) | Proportion of Randomized Subjects Who Have Undetectable HCV RNA 12 Weeks After Last Dose of Study Treatment | 79 participants |
| Other | Proportion of Randomized Subjects Who Have Undetectable HCV RNA 12 Weeks After Last Dose of Study Treatment | 28 participants |
Secondary
Proportion of Randomized Subjects Who Relapse
Proportion of randomized subjects who relapsed was defined as the number of subjects who completed treatment, had undetectable HCV RNA at end of treatment (EOT; Week 24 or Week 48 respectively), and became HCV RNA detectable during antiviral follow-up (24 weeks after EOT).
Time frame: From EOT to Week 48 or Week 72
Population: The population analyzed included all subjects in the Full Analysis (FA) Set. All subjects in the FA Set received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T12PR24 (eRVR+) | Proportion of Randomized Subjects Who Relapse | 9 participants |
| T12PR48 (eRVR+) | Proportion of Randomized Subjects Who Relapse | 1 participants |
| T12PR48 (eRVR-) | Proportion of Randomized Subjects Who Relapse | 5 participants |
| Other | Proportion of Randomized Subjects Who Relapse | 0 participants |
Secondary
Proportion of Subjects Achieving eRVR (Extended RVR), Demonstrated by Achieving Undetectable HCV RNA at Week 4 and at Week 12
Extended rapid viral response is defined undetectable HCV RNA levels at Week 4 and Week 12 (on treatment).
Time frame: Week 4 and Week 12
Population: The population analyzed included all subjects in the Full Analysis (FA) Set. All subjects in the FA Set received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T12PR24 (eRVR+) | Proportion of Subjects Achieving eRVR (Extended RVR), Demonstrated by Achieving Undetectable HCV RNA at Week 4 and at Week 12 | 162 participants |
| T12PR48 (eRVR+) | Proportion of Subjects Achieving eRVR (Extended RVR), Demonstrated by Achieving Undetectable HCV RNA at Week 4 and at Week 12 | 159 participants |
| T12PR48 (eRVR-) | Proportion of Subjects Achieving eRVR (Extended RVR), Demonstrated by Achieving Undetectable HCV RNA at Week 4 and at Week 12 | 0 participants |
| Other | Proportion of Subjects Achieving eRVR (Extended RVR), Demonstrated by Achieving Undetectable HCV RNA at Week 4 and at Week 12 | 31 participants |
Secondary
Proportion of Subjects Who Have Undetectable HCV RNA at the EOT (Week 24 or Week 48 Respectively)
Time frame: Week 24 or Week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T12PR24 (eRVR+) | Proportion of Subjects Who Have Undetectable HCV RNA at the EOT (Week 24 or Week 48 Respectively) | 159 participants |
| T12PR48 (eRVR+) | Proportion of Subjects Who Have Undetectable HCV RNA at the EOT (Week 24 or Week 48 Respectively) | 154 participants |
| T12PR48 (eRVR-) | Proportion of Subjects Who Have Undetectable HCV RNA at the EOT (Week 24 or Week 48 Respectively) | 97 participants |
| Other | Proportion of Subjects Who Have Undetectable HCV RNA at the EOT (Week 24 or Week 48 Respectively) | 59 participants |
Secondary
Proportion of Subjects Who Have Undetectable HCV RNA at Week 72
SVR at Week 72 is defined as achieved SVR24planned and undetectable HCV RNA at Week 72 without any confirmed detectable HCV RNA levels in between those visits.
Time frame: 72 weeks after the last planned dose of study treatment
Population: The population analyzed included all subjects in the Full Analysis (FA) Set. All subjects in the FA Set received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T12PR24 (eRVR+) | Proportion of Subjects Who Have Undetectable HCV RNA at Week 72 | 141 participants |
| T12PR48 (eRVR+) | Proportion of Subjects Who Have Undetectable HCV RNA at Week 72 | 140 participants |
| T12PR48 (eRVR-) | Proportion of Subjects Who Have Undetectable HCV RNA at Week 72 | 76 participants |
| Other | Proportion of Subjects Who Have Undetectable HCV RNA at Week 72 | 20 participants |
95% CI: [-7.7, 6.8]
95% CI: [0.49, 1.82]
Secondary
Safety and Tolerability as Assessed by Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 72
Population: The population analyzed included all subjects who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T12PR24 (eRVR+) | Safety and Tolerability as Assessed by Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Subjects With AEs | 161 participants |
| T12PR24 (eRVR+) | Safety and Tolerability as Assessed by Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Subjects With SAEs | 4 participants |
| T12PR48 (eRVR+) | Safety and Tolerability as Assessed by Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Subjects With SAEs | 16 participants |
| T12PR48 (eRVR+) | Safety and Tolerability as Assessed by Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Subjects With AEs | 160 participants |
| T12PR48 (eRVR-) | Safety and Tolerability as Assessed by Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Subjects With AEs | 117 participants |
| T12PR48 (eRVR-) | Safety and Tolerability as Assessed by Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Subjects With SAEs | 7 participants |
| Other | Safety and Tolerability as Assessed by Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Subjects With AEs | 99 participants |
| Other | Safety and Tolerability as Assessed by Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Subjects With SAEs | 22 participants |