Genotype 1 Chronic Hepatitis C, Treatment Naive
Conditions
Keywords
Genotype 1 chronic hepatitis C, VX-950-C211, VX-950, IL28B, Telaprevir, Hepatitis C, BID, Q8h, SOC
Brief summary
The purpose of this study is to evaluate the effectiveness of telaprevir administered twice daily versus every 8 hours in combination with Peg-IFN-alfa-2a and ribavirin in treatment-naïve participants with chronic HCV genotype 1 infection.
Detailed description
This is a randomized (study drug assigned by chance), open-label (all persons know the study drug assignment) multicenter study to evaluate the effectiveness of telaprevir administered orally as 1125 milligram (mg) twice daily versus 750mg every 8 hours in combination with Peg-IFN-alfa-2a, administered via intramuscular injection once a week, and ribavirin, administered as an oral tablet twice a day, in treatment-naïve study participants with chronic hepatitis C virus (HCV) genotype 1 infection. Telaprevir will be given orally (by mouth) from Day 1 through Week 12 as 3 tablets (1125mg) twice daily or 2 tablets (750mg) every 8 hours. Peg-IFN-alfa-2a will be administered once a week as an injection under the skin (180 microgram/week) from Day 1 through Week 24 or 48 (based on the patient's treatment response on week 4). Ribavirin is administered orally (by mouth) twice daily from Day 1 through Week 24 or 48 (based on the participant's treatment response on week 4) as 1,000-1,200 mg per day. After the end of treatment (Week 24, Week 48, or at early discontinuation of all study drugs), participants with undetectable HCV RNA at end of treatment will be required to attend follow-up visits until Week 72 safety/tolerability assessments will be performed throughout the treatment period and during the follow-up period.
Interventions
DRUGRibavirin
Ribavirin (RBV) 1000-1200 milligram (mg) per day (weight dependent) twice daily regimen oral tablets for 24 or 48 weeks depending on the patient's treatment response at week 4
DRUGTelaprevir
1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks
DRUGPegylated interferon alfa-2a
180 microgram (µg) per week, subcutaneous injection, for 24 or 48 weeks Pegylated interferon alfa-2a 180 microgram (µg) per week subcutaneous injection for 24 or 48 weeks depending on the patient's treatment response at week 4
Sponsors
Vertex Pharmaceuticals Incorporated
Janssen Infectious Diseases BVBA
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
* Patient has chronic HCV infection genotype 1 with HCV RNA level \> 1,000 IU/mL * Patients should not have had any previous treatment for hepatitis C * Patient must have documentation of a liver biopsy within 2 years before the screening visit or the patient must agree to have a biopsy performed within the screening period * Patients with cirrhosis should have serum alpha-fetoprotein (AFP) \<= 50 ng/mL. If AFP \> 50 ng/mL, absence of a mass must be demonstrated by ultrasound within the screening period * A female patient of childbearing potential and a nonvasectomized male patient who has a female partner of childbearing potential must agree to the use of 2 effective methods of birth control from screening until 6 months (female patient) or 7 months (male patient) after the last dose of RBV.
Exclusion criteria
* Patient is infected or co-infected with HCV of another genotype than genotype 1 and/or patient is infected with more than one genotype subtype * Patient has a pre-existing psychiatric condition * Patient has history of decompensated liver disease or shows evidence of significant liver disease in addition to hepatitis C * Patient has human immunodeficiency virus (HIV) or hepatitis B virus (HBV) co-infection * Patient has active malignant disease or history of malignant disease within the past 5 years (with the exception of treated basal cell carcinoma).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After the Last Planned Dose of Study Drugs (SVR12 Planned) | End of trial, 12 weeks after last planned dose | The table below shows the percentage of participants achieving Sustained Virologic Response 12 weeks after last planned dose of study medication (SVR12 planned). SVR was defined as having Hepatitis C Virus (HCV) ribonucleic acid (RNA) levels less than 25 international units/milliliter (IU/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 72 Weeks After the Start of Study Medication (SVR72 Planned) | End of trial, 72 weeks after the start of study medication | The table below shows the percentage of participants achieving SVR 72 weeks after the start of study medication (SVR72 planned). SVR was defined as having plasma Hepatitis C Virus (HCV) ribonucleic acid (RNA) levels less than 25 IU/mL, target not detected, at end of treatment and up to 72 weeks after start of study medication (i.e., no confirmed detectable HCV RNA in between). |
| Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points. | Baseline, Week 4 and Week 4+12. | The table below shows the percentage of participants with undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels, which means less than 25 IU/ml, target not detected, at different time points during the study. |
| Percentage of Participants With Sustained Virologic Response 24 Weeks After the Last Planned Dose of Study Drugs (SVR24 Planned) | End of trial, 24 weeks after last planned dose | The table below shows the percentage of participants achieving SVR 24 weeks after the last planned dose of study medication. SVR was defined as having Hepatitis C Virus (HCV) ribonucleic acid (RNA) levels less than 25 international units/milliliter (IU/mL). The response for T12(b.i.d)/PR group is higher than that after 12 weeks because HCV RNA data for two participants were missing for SVR assessment at that time. Consequently, by definition of SVR12, they were counted as not having achieved SVR12. |
| Percentage of Participants Who Relapsed During Follow-up Period | During Follow-Up (24 weeks after the last dose of study drug) | The table below shows the percentage of participants who relapsed (ie, those having confirmed detectable hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] during the 12-week follow-up period after previous HCV RNA \<25 IU/mL, target not detected, at end of treatment). |
| Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned) | End of trial, 12 weeks after the last planned dose | The table below shows the effect of interleukin 28B (IL28B) gene's subtype (CC, CT or TT genotype) on the primary outcome measure: SVR12 planned. |
| Percentage of Participants With On-treatment Virologic Failure Which Required Them to Permanently Discontinue All Study Drugs | Week 4, 12, 24, 32, 40 | The table below shows the percentage of participants who met a stopping rule, defined as having a hepatitis C virus (HCV) ribonucleic acid (RNA) value at Week 4 \>1000 IU/mL and at Weeks 12, 24, 32 and 40 ≥25 IU/mL. |
Countries
Australia, Austria, Belgium, Brazil, France, Germany, Ireland, Mexico, Poland, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
This study evaluated the effectiveness of telaprevir administered twice daily versus every 8 hours in combination with pegylated interferon and ribavirin in treatment-naïve participants with chronic HCV genotype 1 infection.
Pre-assignment details
The study was conducted between 15 November 2010 and 02 August 2012 and recruited participants from 125 study centers in 14 countries worldwide. 744 participants were initially enrolled and 740 out of them randomly allocated to the 2 treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| T12(q8h)/PR Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4. | 371 |
| T12(b.i.d.)/PR Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4. | 369 |
| Total | 740 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 18 | 22 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Switch To Commercially Available Medicat | 1 | 4 |
| Overall Study | Withdrawal by Subject | 13 | 13 |
Baseline characteristics
| Characteristic | T12(q8h)/PR | T12(b.i.d.)/PR | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 0 Participants | 3 Participants |
| Age, Categorical >=65 years | 17 Participants | 7 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 351 Participants | 362 Participants | 713 Participants |
| Age, Continuous | 48 years | 47.5 years | 47.7 years |
| Region of Enrollment Australia | 28 participants | 28 participants | 56 participants |
| Region of Enrollment Brazil | 20 participants | 21 participants | 41 participants |
| Region of Enrollment Europe | 192 participants | 179 participants | 371 participants |
| Region of Enrollment Mexico | 5 participants | 4 participants | 9 participants |
| Region of Enrollment North-America | 126 participants | 137 participants | 263 participants |
| Sex: Female, Male Female | 136 Participants | 160 Participants | 296 Participants |
| Sex: Female, Male Male | 235 Participants | 209 Participants | 444 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 | 359 / 371 | 358 / 369 | 717 / 740 |
| serious Total, serious adverse events | 35 / 371 | 28 / 369 | 63 / 740 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After the Last Planned Dose of Study Drugs (SVR12 Planned)
The table below shows the percentage of participants achieving Sustained Virologic Response 12 weeks after last planned dose of study medication (SVR12 planned). SVR was defined as having Hepatitis C Virus (HCV) ribonucleic acid (RNA) levels less than 25 international units/milliliter (IU/mL).
Time frame: End of trial, 12 weeks after last planned dose
Population: All analyses were performed on the full analysis (FA) set, which was defined as all randomized subjects who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T12(q8h)/PR | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After the Last Planned Dose of Study Drugs (SVR12 Planned) | 72.8 percentage of participants with response |
| T12(b.i.d.)/PR | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After the Last Planned Dose of Study Drugs (SVR12 Planned) | 74.3 percentage of participants with response |
95% CI: [-4.9, 12]Regression, Logistic
Secondary
Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points.
The table below shows the percentage of participants with undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels, which means less than 25 IU/ml, target not detected, at different time points during the study.
Time frame: Baseline, Week 4 and Week 4+12.
Population: All analyses were performed on the full analysis (FA) set, which was defined as all randomized subjects who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T12(q8h)/PR | Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points. | Baseline | 0 percentage of participants with response |
| T12(q8h)/PR | Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points. | at Week 4 | 67.4 percentage of participants with response |
| T12(q8h)/PR | Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points. | at Week 4 and Week 12 | 63.1 percentage of participants with response |
| T12(b.i.d.)/PR | Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points. | Baseline | 0 percentage of participants with response |
| T12(b.i.d.)/PR | Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points. | at Week 4 | 69.4 percentage of participants with response |
| T12(b.i.d.)/PR | Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points. | at Week 4 and Week 12 | 66.1 percentage of participants with response |
Secondary
Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned)
The table below shows the effect of interleukin 28B (IL28B) gene's subtype (CC, CT or TT genotype) on the primary outcome measure: SVR12 planned.
Time frame: End of trial, 12 weeks after the last planned dose
Population: All analyses were performed on the full analysis (FA) set, which was defined as all randomized subjects who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T12(q8h)/PR | Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned) | CC genotype (n = 108; n = 103) | 86.8 percentage of participants with response |
| T12(q8h)/PR | Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned) | CT genotype (n = 207; n = 207) | 67.8 percentage of participants with response |
| T12(q8h)/PR | Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned) | TT genotype (n = 56; n = 59) | 64.9 percentage of participants with response |
| T12(b.i.d.)/PR | Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned) | CC genotype (n = 108; n = 103) | 92.4 percentage of participants with response |
| T12(b.i.d.)/PR | Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned) | CT genotype (n = 207; n = 207) | 67.5 percentage of participants with response |
| T12(b.i.d.)/PR | Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned) | TT genotype (n = 56; n = 59) | 65.5 percentage of participants with response |
Secondary
Percentage of Participants Who Relapsed During Follow-up Period
The table below shows the percentage of participants who relapsed (ie, those having confirmed detectable hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] during the 12-week follow-up period after previous HCV RNA \<25 IU/mL, target not detected, at end of treatment).
Time frame: During Follow-Up (24 weeks after the last dose of study drug)
Population: The analysis was performed on subjects with HCV RNA \<25 IU/mL at the planned end of treatment, which included all randomized participants who received at least one dose of study drug and had data at the follow-up visit performed 24 weeks after the last dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T12(q8h)/PR | Percentage of Participants Who Relapsed During Follow-up Period | 7.2 percentage of participants |
| T12(b.i.d.)/PR | Percentage of Participants Who Relapsed During Follow-up Period | 7.7 percentage of participants |
Secondary
Percentage of Participants With On-treatment Virologic Failure Which Required Them to Permanently Discontinue All Study Drugs
The table below shows the percentage of participants who met a stopping rule, defined as having a hepatitis C virus (HCV) ribonucleic acid (RNA) value at Week 4 \>1000 IU/mL and at Weeks 12, 24, 32 and 40 ≥25 IU/mL.
Time frame: Week 4, 12, 24, 32, 40
Population: All analyses were performed on the full analysis (FA) set, which was defined as all randomized subjects who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T12(q8h)/PR | Percentage of Participants With On-treatment Virologic Failure Which Required Them to Permanently Discontinue All Study Drugs | 9.7 percentage of participants |
| T12(b.i.d.)/PR | Percentage of Participants With On-treatment Virologic Failure Which Required Them to Permanently Discontinue All Study Drugs | 10.3 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 24 Weeks After the Last Planned Dose of Study Drugs (SVR24 Planned)
The table below shows the percentage of participants achieving SVR 24 weeks after the last planned dose of study medication. SVR was defined as having Hepatitis C Virus (HCV) ribonucleic acid (RNA) levels less than 25 international units/milliliter (IU/mL). The response for T12(b.i.d)/PR group is higher than that after 12 weeks because HCV RNA data for two participants were missing for SVR assessment at that time. Consequently, by definition of SVR12, they were counted as not having achieved SVR12.
Time frame: End of trial, 24 weeks after last planned dose
Population: All analyses were performed on the full analysis (FA) set, which was defined as all randomized subjects who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T12(q8h)/PR | Percentage of Participants With Sustained Virologic Response 24 Weeks After the Last Planned Dose of Study Drugs (SVR24 Planned) | 72.8 percentage of participants with response |
| T12(b.i.d.)/PR | Percentage of Participants With Sustained Virologic Response 24 Weeks After the Last Planned Dose of Study Drugs (SVR24 Planned) | 74.8 percentage of participants with response |
Secondary
Percentage of Participants With Sustained Virologic Response 72 Weeks After the Start of Study Medication (SVR72 Planned)
The table below shows the percentage of participants achieving SVR 72 weeks after the start of study medication (SVR72 planned). SVR was defined as having plasma Hepatitis C Virus (HCV) ribonucleic acid (RNA) levels less than 25 IU/mL, target not detected, at end of treatment and up to 72 weeks after start of study medication (i.e., no confirmed detectable HCV RNA in between).
Time frame: End of trial, 72 weeks after the start of study medication
Population: All analyses were performed on the full analysis (FA) set, which was defined as all randomized subjects who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T12(q8h)/PR | Percentage of Participants With Sustained Virologic Response 72 Weeks After the Start of Study Medication (SVR72 Planned) | 69.0 percentage of participants with response |
| T12(b.i.d.)/PR | Percentage of Participants With Sustained Virologic Response 72 Weeks After the Start of Study Medication (SVR72 Planned) | 70.2 percentage of participants with response |