Genotype 1 Chronic Hepatitis C
Conditions
Keywords
Genotype 1 chronic Hepatitis C, VX-950HPC3007, VX-950, Hepatitis C, Telaprevir, HCV
Brief summary
The purpose of this study is to determine the effectiveness, safety and tolerability of telaprevir administered as 750 mg every 8 hours (q8h) in combination with pegylated interferon (Peg-IFN)-alfa-2a and ribavirin (RBV) in treatment-naïve and treatment-experienced Russian participants with genotype 1 chronic hepatitis C.
Detailed description
This is an open-label (all persons know the study drug assignment), multicenter study in treatment-naïve (participant did not receive any previous treatment for the treatment of hepatitis C) and treatment-experienced (participant did receive previous treatment for hepatitis C) Russian participants with genotype 1 chronic hepatitis C. After a screening period of approximately 4 weeks, participants will be treated for 12 weeks with telaprevir 750 mg every 8 hours in combination with Peg-IFN-alfa-2a and RBV followed by 12 or 36 weeks of treatment with Peg-IFN-alfa-2a and RBV alone depending on their liver disease status, response to previous treatment and individual virologic response during treatment in this study. After the treatment period, there is a follow-up phase of at least 12 weeks.
Interventions
DRUGTelaprevir
Telaprevir Type = exact number, unit = mg, number = 750, form = tablet, route = oral. Telaprevir 750 mg (2 oral tablets) is taken every 8 hours for 12 weeks
Pegylated-interferon-alfa-2a type = exact number, unit = microgram, number = 180, form = injection, route = subcutaneous. 180 microgram (µg) per week, subcutaneous injection, for 24 or 48 weeks
DRUGRibavirin
Ribavirin Type = exact, number = 1000 or 1200, unit = mg, form = tablet, route = oral. 1000mg (if participant's weight is \< 75kg) or 1200mg (if participant's weight is \>= 75kg) per day for 24 or 48 weeks.
Sponsors
Janssen-Cilag International NV
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Participant has genotype 1 chronic hepatitis C with HCV RNA level \>1000 IU/mL * Participant is either treatment-naïve and did not receive any previous treatment with any approved or investigational drug or drug regimen for the treatment of hepatitis C, or participant is treatment-experienced who did not achieve sustained virologic response (SVR) 24 weeks after at least 1 prior course of Peg-IFN/RBV therapy (null-responder, partial-responder or viral relapse) * Participant must have documentation of liver biopsy or fibroscan within 2 years before the screening visit or agree to have a biopsy or fibroscan within the screening period unless histological cirrhosis was demonstrated by a biopsy or fibroscan \> 2 years ago prior to screening * A female participant of childbearing potential and a nonvasectomized male participant 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 participant ) or 7 months (male participant) after the last dose of RBV
Exclusion criteria
* Prior non-responder that is classified as a viral breakthrough participant * Participant is infected or co-infected with HCV of another genotype than genotype 1 * Participant has history of decompensated liver disease or shows evidence of significant liver disease in addition to hepatitis C * Participant has human immunodeficiency virus (HIV) or hepatitis B virus (HBV) co-infection * Participant has active malignant disease or history of malignant disease within the past 5 years (with the exception of treated basal cell carcinoma or hepatocellular carcinoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Extended Rapid Virologic Response (eRVR) | Week 4 and Week 12 | A eRVR is defined as having hepatitis C virus (HCV) ribonucleic acid (RNA) less than 25 IU/mL, (target not detected) at Weeks 4 and 12 of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Baseline (Week 0), Week 4, Week 8, Week 12, Week 24, Week 32, Week 40, and Week 48 | Changes from baseline in log10 HCV RNA levels were calculated. |
| Number of Participants With Rapid Virologic Response (RVR) at Week 4 | Week 4 | A RVR is defined as having hepatitis C virus (HCV) ribonucleic acid (RNA) less than 25 IU/mL, (target not detected) at Week 4 |
| Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Weeks 8, 12, 24, 32, 40 and 48 | The table below shows number of participants with HCV RNA Less than 25 IU/mL, (target not detected) at Weeks 8, 12, 24, 32, 40 and 48. Only 3 treatment-naive and 14 Treatment-experienced participants were assigned to receive study treatment after Week 24. Only participants still receiving Treatment were assessed at 32, 40, and 48 weeks. |
| Number of Participants With Virologic Failure | Week 4, Week 8, Week 12, Week 24, Week 32, or Week 40 | Virologic failure is defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels more than 1,000 IU/mL at Weeks 4, 8, 12, 24, 32, or 40. |
| Number of Participants in Each Specific Category of Treatment Outcome | From Day 1 (Baseline) up to Follow-up visit (Week 36 or Week 60) | Participants were evaluated for following 4 categories of treatment outcome;Sustained Virologic Response 12 Weeks After Last Planned Dose of Study Medication(SVR12):hepatitis C virus (HCV)ribonucleic acid (RNA)\<25 IU/mL(target not detected)12 weeks after last planned dose of study medication;Relapse:HCV RNA =\>25 IU/mL during follow-up period after previous HCV RNA\<25 IU/mL at planned end of treatment(EOT)\[Week 24 or Week 48\] and participant did not achieve SVR12planned;On treatment virologic failure:meeting virologic stopping rule and/or having detectable HCV RNA at EOT with viral breakthrough(having a confirmed increase \>1 log 10 in HCV RNA level from the lowest level reached or confirmed value of HCV RNA \>100 IU/mL in participants whose HCV RNA has previously become \<25 IU/mL during treatment).Stopping rule defined as HCV RNA value \>1000 IU/mL at Week 4, 8 or 12 or detectable HCV RNA at Week 24, 32 or 40;Other:HCV RNA \<25 IU/mL at actual EOT and never HCV RNA =\>25 IU/mL thereafter. |
Countries
Russia
Participant flow
Recruitment details
The study was conducted at 5 sites in Russia.
Pre-assignment details
Of the 39 participants screened, 36 participants (16 treatment-naïve/ 20 treatment-experienced) were enrolled and treated.
Participants by arm
| Arm | Count |
|---|---|
| Treatment-naïve Treatment naïve participants received telaprevir 750 mg every 8 hours for 12 weeks in combination with Peg-IFN alfa-2a 180 microgram once a week and RBV 1000 - 1200 mg daily (dependent on weight) for 24 or 48 weeks. Total treatment duration is based on participant's prior treatment status, liver disease status, and individual on-treatment virologic response in this study. | 16 |
| Treatment-experienced Treatment-experienced participants received telaprevir 750 mg every 8 hours for 12 weeks in combination with Peg-IFN alfa-2a 180 microgram once a week and RBV 1000 - 1200 mg daily (dependent on weight) for 24 or 48 weeks. Total treatment duration is based on participant's prior treatment status, liver disease status, and individual on-treatment virologic response in this study. | 20 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Treatment-naïve | Treatment-experienced | Total |
|---|---|---|---|
| Age, Customized <= 45 years | 13 Participants | 12 Participants | 25 Participants |
| Age, Customized > 65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Customized Between 45 and 65 years | 2 Participants | 8 Participants | 10 Participants |
| Sex: Female, Male Female | 9 Participants | 13 Participants | 22 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 16 | 19 / 20 |
| serious Total, serious adverse events | 0 / 16 | 0 / 20 |
Outcome results
Primary
Number of Participants With Extended Rapid Virologic Response (eRVR)
A eRVR is defined as having hepatitis C virus (HCV) ribonucleic acid (RNA) less than 25 IU/mL, (target not detected) at Weeks 4 and 12 of treatment.
Time frame: Week 4 and Week 12
Population: Full analysis (FA) population: All participants who received at least one dose of the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment-naïve | Number of Participants With Extended Rapid Virologic Response (eRVR) | 13 Participants |
| Treatment-experienced | Number of Participants With Extended Rapid Virologic Response (eRVR) | 18 Participants |
Secondary
Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Changes from baseline in log10 HCV RNA levels were calculated.
Time frame: Baseline (Week 0), Week 4, Week 8, Week 12, Week 24, Week 32, Week 40, and Week 48
Population: Full analysis (FA) population: All participants who received at least one dose of the study medication. n signifies number of participants who were evaluable at each specified timepoint for each arm, respectively.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment-naïve | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Baseline (n=16, 20) | 6.20 Log 10 IU/mL |
| Treatment-naïve | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 24 (n=14, 19) | -5.53 Log 10 IU/mL |
| Treatment-naïve | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 8 (n=16,19) | -5.50 Log 10 IU/mL |
| Treatment-naïve | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 32 (n=2, 12) | -5.30 Log 10 IU/mL |
| Treatment-naïve | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 4 (n=16, 20) | -5.47 Log 10 IU/mL |
| Treatment-naïve | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 40 (n=2, 12) | -5.30 Log 10 IU/mL |
| Treatment-naïve | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 48 (n=2, 12) | -3.14 Log 10 IU/mL |
| Treatment-naïve | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 12 (n=15,19) | -5.46 Log 10 IU/mL |
| Treatment-experienced | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 48 (n=2, 12) | -5.46 Log 10 IU/mL |
| Treatment-experienced | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Baseline (n=16, 20) | 6.10 Log 10 IU/mL |
| Treatment-experienced | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 4 (n=16, 20) | -5.33 Log 10 IU/mL |
| Treatment-experienced | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 8 (n=16,19) | -5.39 Log 10 IU/mL |
| Treatment-experienced | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 12 (n=15,19) | -5.39 Log 10 IU/mL |
| Treatment-experienced | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 24 (n=14, 19) | -5.39 Log 10 IU/mL |
| Treatment-experienced | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 32 (n=2, 12) | -5.46 Log 10 IU/mL |
| Treatment-experienced | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 40 (n=2, 12) | -5.46 Log 10 IU/mL |
Secondary
Number of Participants in Each Specific Category of Treatment Outcome
Participants were evaluated for following 4 categories of treatment outcome;Sustained Virologic Response 12 Weeks After Last Planned Dose of Study Medication(SVR12):hepatitis C virus (HCV)ribonucleic acid (RNA)\<25 IU/mL(target not detected)12 weeks after last planned dose of study medication;Relapse:HCV RNA =\>25 IU/mL during follow-up period after previous HCV RNA\<25 IU/mL at planned end of treatment(EOT)\[Week 24 or Week 48\] and participant did not achieve SVR12planned;On treatment virologic failure:meeting virologic stopping rule and/or having detectable HCV RNA at EOT with viral breakthrough(having a confirmed increase \>1 log 10 in HCV RNA level from the lowest level reached or confirmed value of HCV RNA \>100 IU/mL in participants whose HCV RNA has previously become \<25 IU/mL during treatment).Stopping rule defined as HCV RNA value \>1000 IU/mL at Week 4, 8 or 12 or detectable HCV RNA at Week 24, 32 or 40;Other:HCV RNA \<25 IU/mL at actual EOT and never HCV RNA =\>25 IU/mL thereafter.
Time frame: From Day 1 (Baseline) up to Follow-up visit (Week 36 or Week 60)
Population: Full analysis (FA) population: All participants who received at least one dose of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment-naïve | Number of Participants in Each Specific Category of Treatment Outcome | SVR12 | 14 Participants |
| Treatment-naïve | Number of Participants in Each Specific Category of Treatment Outcome | Relapse | 0 Participants |
| Treatment-naïve | Number of Participants in Each Specific Category of Treatment Outcome | On treatment virologic failure | 1 Participants |
| Treatment-naïve | Number of Participants in Each Specific Category of Treatment Outcome | Other | 1 Participants |
| Treatment-experienced | Number of Participants in Each Specific Category of Treatment Outcome | Other | 1 Participants |
| Treatment-experienced | Number of Participants in Each Specific Category of Treatment Outcome | SVR12 | 16 Participants |
| Treatment-experienced | Number of Participants in Each Specific Category of Treatment Outcome | On treatment virologic failure | 2 Participants |
| Treatment-experienced | Number of Participants in Each Specific Category of Treatment Outcome | Relapse | 1 Participants |
Secondary
Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48
The table below shows number of participants with HCV RNA Less than 25 IU/mL, (target not detected) at Weeks 8, 12, 24, 32, 40 and 48. Only 3 treatment-naive and 14 Treatment-experienced participants were assigned to receive study treatment after Week 24. Only participants still receiving Treatment were assessed at 32, 40, and 48 weeks.
Time frame: Weeks 8, 12, 24, 32, 40 and 48
Population: Full analysis (FA) population: All participants who received at least one dose of the study medication. n signifies number of participants who were evaluable at each specified timepoint for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment-naïve | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Week 8 (n=16, 20) | 16 Participants |
| Treatment-naïve | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Week 12 (n=16, 20) | 15 Participants |
| Treatment-naïve | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Week 24 (n=16, 20) | 15 Participants |
| Treatment-naïve | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Week 32 (n=3, 14) | 2 Participants |
| Treatment-naïve | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Week 40 (n=3, 14) | 2 Participants |
| Treatment-naïve | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Week 48 (n=3, 14) | 1 Participants |
| Treatment-experienced | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Week 40 (n=3, 14) | 12 Participants |
| Treatment-experienced | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Week 8 (n=16, 20) | 19 Participants |
| Treatment-experienced | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Week 32 (n=3, 14) | 12 Participants |
| Treatment-experienced | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Week 12 (n=16, 20) | 19 Participants |
| Treatment-experienced | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Week 48 (n=3, 14) | 12 Participants |
| Treatment-experienced | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 | Week 24 (n=16, 20) | 18 Participants |
Secondary
Number of Participants With Rapid Virologic Response (RVR) at Week 4
A RVR is defined as having hepatitis C virus (HCV) ribonucleic acid (RNA) less than 25 IU/mL, (target not detected) at Week 4
Time frame: Week 4
Population: Full analysis (FA) population: All participants who received at least one dose of the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment-naïve | Number of Participants With Rapid Virologic Response (RVR) at Week 4 | 14 Participants |
| Treatment-experienced | Number of Participants With Rapid Virologic Response (RVR) at Week 4 | 18 Participants |
Secondary
Number of Participants With Virologic Failure
Virologic failure is defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels more than 1,000 IU/mL at Weeks 4, 8, 12, 24, 32, or 40.
Time frame: Week 4, Week 8, Week 12, Week 24, Week 32, or Week 40
Population: Full analysis (FA) population: All participants who received at least one dose of the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment-naïve | Number of Participants With Virologic Failure | 1 Participants |
| Treatment-experienced | Number of Participants With Virologic Failure | 2 Participants |