Chronic Hepatitis C
Conditions
Brief summary
Study the effectiveness of telaprevir (VX-950) in combination with Pegylated Interferon Alfa 2a (Peg-IFN-alfa-2a) and Ribavirin (RBV) in reducing plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels
Interventions
DRUGTelaprevir
tablet
DRUGRibavirin
tablet
Solution for injection
OTHERPlacebo
matching placebo tablet
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Hepatitis C virus Genotype 1 with detectable plasma hepatitis C virus RNA * Have been infected with hepatitis C virus for greater than (\>) 6 months * Seronegative for hepatitis B surface antigen and Human Immunodeficiency Virus 1 and 2 * Must agree to use 2 methods of contraception, including 1 barrier method, during and for 24 weeks after the completion of the study (unless the subject is a female of documented non-child-bearing potential) * Female subjects must have a negative pregnancy test at all visits before the first dose
Exclusion criteria
* Received any approved or investigational drug or drug regimen for the treatment of hepatitis C * Any medical contraindications to Pegylated Interferon Alfa 2a or Ribavirin therapy * Any other cause of significant liver disease in addition to hepatitis C; this may include but is not limited to, hepatitis B, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, Nonalcoholic Steatohepatitis or primary biliary cirrhosis * Diagnosed or suspected hepatocellular carcinoma * Histologic evidence of hepatic cirrhosis (including compensated cirrhosis) based on a liver biopsy taken within 2 years before study start * Alcohol abuse or excessive use in the last 12 months * Participation in any investigational drug study within 90 days before drug administration or participation in more than 2 drug studies in the last 12 months (exclusive of the current study)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing | 24 weeks after the completion of study drug dosing (up to Week 72) | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing | 12 weeks after the completion of study drug dosing (up to Week 60) | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). |
| Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to Week 48 | AE: any adverse change from the subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Study drug includes all investigational agents (including placebo, if applicable) administered during the course of the study. |
| Number of Subjects With Viral Relapse | After last dose of study drug up to antiviral follow-up (up to Week 72) | Viral relapse was defined as having detectable HCV RNA during antiviral follow-up. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). |
| Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir | Day 1, 4, 8, 15, 22, 29, 43, 57, 71, 85 | Only subjects who received telaprevir were to be analyzed for this outcome. Maximum, minimum and average plasma concentrations observed during assessment period were reported. |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
A total of 263 subjects were enrolled, of which 13 subjects discontinued the study prior to study drug administration. A total of 250 subjects started treatment.
Participants by arm
| Arm | Count |
|---|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week Placebo (PBO) matched to telaprevir tablet orally thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (\<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (\>=) 75 kg, for 48 weeks. | 75 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. | 79 |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 24 weeks. | 79 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 12 weeks. | 17 |
| Total | 250 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 11 | 18 | 4 |
| Overall Study | Lost to Follow-up | 3 | 2 | 0 | 0 |
| Overall Study | Noncompliant | 1 | 7 | 3 | 0 |
| Overall Study | Other | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 2 | 3 | 1 | 0 |
| Overall Study | Virologic Stopping Rule | 20 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 3 | 0 |
Baseline characteristics
| Characteristic | Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 79 Participants | 79 Participants | 75 Participants | 17 Participants | 250 Participants |
| Age, Continuous | 48.7 years STANDARD_DEVIATION 7.4 | 48.4 years STANDARD_DEVIATION 7.6 | 46.8 years STANDARD_DEVIATION 8.7 | 49.1 years STANDARD_DEVIATION 8 | 48.1 years STANDARD_DEVIATION 7.9 |
| Region of Enrollment North America | 79 participants | 79 participants | 75 participants | 17 participants | 250 participants |
| Sex: Female, Male Female | 31 Participants | 25 Participants | 32 Participants | 5 Participants | 93 Participants |
| Sex: Female, Male Male | 48 Participants | 54 Participants | 43 Participants | 12 Participants | 157 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 | 75 / 75 | 79 / 79 | 79 / 79 | 17 / 17 |
| serious Total, serious adverse events | 4 / 75 | 5 / 79 | 10 / 79 | 3 / 17 |
Outcome results
Primary
Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL).
Time frame: 24 weeks after the completion of study drug dosing (up to Week 72)
Population: The Full Analysis set included all randomized subjects who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing | 41.3 percentage of participants |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing | 67.1 percentage of participants |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing | 60.8 percentage of participants |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing | 35.3 percentage of participants |
p-value: 0.001495% CI: [1.525, 5.842]Regression, Logistic
p-value: 0.020495% CI: [1.127, 4.178]Regression, Logistic
Secondary
Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir
Only subjects who received telaprevir were to be analyzed for this outcome. Maximum, minimum and average plasma concentrations observed during assessment period were reported.
Time frame: Day 1, 4, 8, 15, 22, 29, 43, 57, 71, 85
Population: Pharmacokinetic population included all subjects who provided pharmacokinetic assessments and had evaluable and interpretable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir | Cmax | 3032.48 nanogram per milliliter (ng/mL) | Standard Deviation 756.93 |
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir | Cmin | 2235.51 nanogram per milliliter (ng/mL) | Standard Deviation 618.37 |
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir | Cavg | 2738.46 nanogram per milliliter (ng/mL) | Standard Deviation 699.06 |
Secondary
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any adverse change from the subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Study drug includes all investigational agents (including placebo, if applicable) administered during the course of the study.
Time frame: Baseline up to Week 48
Population: The Full Analysis set included all randomized subjects who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 75 participants |
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 4 participants |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 5 participants |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 79 participants |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 79 participants |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 10 participants |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 17 participants |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 3 participants |
Secondary
Number of Subjects With Viral Relapse
Viral relapse was defined as having detectable HCV RNA during antiviral follow-up. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL).
Time frame: After last dose of study drug up to antiviral follow-up (up to Week 72)
Population: Analysis population included subjects who completed their assigned study drug treatment and had undetectable HCV RNA at the completion of treatment (up to Week 48).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | Number of Subjects With Viral Relapse | 8 participants |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | Number of Subjects With Viral Relapse | 3 participants |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | Number of Subjects With Viral Relapse | 1 participants |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | Number of Subjects With Viral Relapse | 3 participants |
Secondary
Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL).
Time frame: 12 weeks after the completion of study drug dosing (up to Week 60)
Population: The Full Analysis set included all randomized subjects who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing | 36.0 percentage of participants |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing | 58.2 percentage of participants |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing | 53.2 percentage of participants |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing | 35.3 percentage of participants |
p-value: 0.005195% CI: [1.331, 5.025]Regression, Logistic
p-value: 0.041895% CI: [1.026, 3.807]Regression, Logistic