Hepatitis C, HIV Infections
Conditions
Keywords
VX-950, INCIVEK, INCIVO
Brief summary
The purpose of this study is to determine whether the combination of telaprevir, peginterferon alfa-2a, and ribavirin is safe and effective in treating hepatitis C virus (HCV) infection in subjects who are infected with both HCV and human immunodeficiency virus (HIV).
Interventions
DRUGtelaprevir or matching placebo
Tablet, Oral, 750 mg, q8h, 12 weeks
BIOLOGICALpeginterferon alfa-2a
Subcutaneous injection, 180 μg, once weekly, 48 weeks
DRUGribavirin (fixed dose)
Tablet, Oral, 800 mg, b.i.d., 48 weeks
DRUGribavirin (weight-based dose)
Tablet, Oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
Sponsors
Tibotec Pharmaceutical Limited
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
* Chronic, genotype 1, hepatitis C with detectable HCV RNA * HIV-1 infection for \>6 months * Documentation of a liver biopsy within 1 year before the screening visit showing evidence of hepatitis (demonstrated by inflammation and/or fibrosis)
Exclusion criteria
* Previous treatment with any approved or investigational drug or drug regimen for the treatment of hepatitis C * Previous treatment with interferon or ribavirin * Evidence of hepatic decompensation in cirrhotic subjects * Subjects who have participated in a clinical study involving administration of an investigational drug within 2 months * Part A only: subjects who have been on a HAART regimen within 12 weeks before study start
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Subjects Achieving Undetectable HCV RNA at Week 12 | 12 weeks after first dose of study drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | 4 and 12 weeks after the first dose of study drug | number of subjects with undetectable HCV RNA |
| Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | 12 weeks after last dose of study drug | — |
| Effect of Efavirenz-based (EFV) and Atazanavir-based (ATV/r) Highly Active Antiretroviral Therapy(HAART) on Telaprevir Exposure | through 12 weeks after first dose of study drug | — |
| Median Trough Plasma Concentration (Ctrough) Ratios of Efavirenz and Tenofovir (Part B Only, Subjects on EFV-based HAART) | through 12 weeks after first dose of study drug | Ctrough ratio of HAART medication with telaprevir (test) and without telaprevir (reference) |
| Median Trough Plasma Concentration (Ctrough) Ratios of Atazanavir (ATZ), Ritonavir, and Tenofovir (Part B Only, Subjects on ATV-based HAART) | through 12 weeks after first dose of study drug | Ctrough of HAART medication with telaprevir (test) and without telaprevir (reference) |
Countries
France, Germany, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A: T/PR Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART. | 7 |
| Part A: Pbo/PR Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART. | 6 |
| Part B: EFV-based HAART + T/PR Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz(EFV)-based highly active antiretroviral therapy(HAART) for the entire 48 week study. | 16 |
| Part B: EFV-based HAART + Pbo/PR Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz(EFV)-based highly active antiretroviral therapy(HAART) for the entire 48 week study. | 8 |
| Part B: ATV/R-based HAART + T/PR Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir(ATV/r)-based highly active antiretroviral therapy(HAART) for the entire 48 week study. | 15 |
| Part B: ATV/R-based HAART + Pbo/PR Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir(ATV/r)-based highly active antiretroviral therapy(HAART) for the entire 48 week study. | 8 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 2 | 2 | 2 | 1 |
| Overall Study | Unable to come to study follow-up visits | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A: T/PR | Total | Part B: ATV/R-based HAART + Pbo/PR | Part B: ATV/R-based HAART + T/PR | Part B: EFV-based HAART + Pbo/PR | Part B: EFV-based HAART + T/PR | Part A: Pbo/PR |
|---|---|---|---|---|---|---|---|
| Age Continuous median (min, max) | 39.4 years | 44.5 years | 39.0 years | 52.0 years | 47.0 years | 47.5 years | 47.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 17 Participants | 3 Participants | 3 Participants | 1 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 42 Participants | 5 Participants | 12 Participants | 7 Participants | 10 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian/Alaska Native | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black/African American | 4 participants | 16 participants | 1 participants | 2 participants | 3 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Other | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White | 2 participants | 42 participants | 7 participants | 13 participants | 5 participants | 12 participants | 3 participants |
| Region of Enrollment Europe | 0 participants | 14 participants | 4 participants | 6 participants | 0 participants | 3 participants | 1 participants |
| Region of Enrollment France | 0 participants | 2 participants | 0 participants | 2 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Germany | 0 participants | 3 participants | 1 participants | 1 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment North America | 7 participants | 46 participants | 4 participants | 9 participants | 8 participants | 13 participants | 5 participants |
| Region of Enrollment Spain | 0 participants | 9 participants | 3 participants | 3 participants | 0 participants | 2 participants | 1 participants |
| Region of Enrollment United States | 7 participants | 46 participants | 4 participants | 9 participants | 8 participants | 13 participants | 5 participants |
| Sex: Female, Male Female | 1 Participants | 7 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 53 Participants | 7 Participants | 13 Participants | 7 Participants | 16 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 38 | 22 / 22 |
| serious Total, serious adverse events | 7 / 38 | 2 / 22 |
Outcome results
Primary
Proportion of Subjects Achieving Undetectable HCV RNA at Week 12
Time frame: 12 weeks after first dose of study drug
Population: Subjects who were randomized and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: T/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 12 | 6 participants |
| Part A: Pbo/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 12 | 2 participants |
| Part B: EFV-based HAART + T/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 12 | 14 participants |
| Part B: EFV-based HAART + Pbo/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 12 | 2 participants |
| Part B: ATV/R-based HAART + T/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 12 | 10 participants |
| Part B: ATV/R-based HAART + Pbo/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 12 | 2 participants |
Secondary
Effect of Efavirenz-based (EFV) and Atazanavir-based (ATV/r) Highly Active Antiretroviral Therapy(HAART) on Telaprevir Exposure
Time frame: through 12 weeks after first dose of study drug
Population: subjects with available plasma concentration data
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: T/PR | Effect of Efavirenz-based (EFV) and Atazanavir-based (ATV/r) Highly Active Antiretroviral Therapy(HAART) on Telaprevir Exposure | Cmin | 0.8842 ratio (test/reference) |
| Part A: T/PR | Effect of Efavirenz-based (EFV) and Atazanavir-based (ATV/r) Highly Active Antiretroviral Therapy(HAART) on Telaprevir Exposure | Cavg | 0.9610 ratio (test/reference) |
| Part A: T/PR | Effect of Efavirenz-based (EFV) and Atazanavir-based (ATV/r) Highly Active Antiretroviral Therapy(HAART) on Telaprevir Exposure | Cmax | 1.0061 ratio (test/reference) |
| Part A: Pbo/PR | Effect of Efavirenz-based (EFV) and Atazanavir-based (ATV/r) Highly Active Antiretroviral Therapy(HAART) on Telaprevir Exposure | Cmin | 1.3059 ratio (test/reference) |
| Part A: Pbo/PR | Effect of Efavirenz-based (EFV) and Atazanavir-based (ATV/r) Highly Active Antiretroviral Therapy(HAART) on Telaprevir Exposure | Cavg | 1.0930 ratio (test/reference) |
| Part A: Pbo/PR | Effect of Efavirenz-based (EFV) and Atazanavir-based (ATV/r) Highly Active Antiretroviral Therapy(HAART) on Telaprevir Exposure | Cmax | 1.0075 ratio (test/reference) |
Secondary
Median Trough Plasma Concentration (Ctrough) Ratios of Atazanavir (ATZ), Ritonavir, and Tenofovir (Part B Only, Subjects on ATV-based HAART)
Ctrough of HAART medication with telaprevir (test) and without telaprevir (reference)
Time frame: through 12 weeks after first dose of study drug
Population: subjects with available concentration data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: T/PR | Median Trough Plasma Concentration (Ctrough) Ratios of Atazanavir (ATZ), Ritonavir, and Tenofovir (Part B Only, Subjects on ATV-based HAART) | Atazanavir (N=12 T/PR, N=6 Pbo/PR) | 1.16 ratio (test/reference) |
| Part A: T/PR | Median Trough Plasma Concentration (Ctrough) Ratios of Atazanavir (ATZ), Ritonavir, and Tenofovir (Part B Only, Subjects on ATV-based HAART) | Tenofovir (N=13 T/PR, N=7 Pbo/PR) | 0.75 ratio (test/reference) |
| Part A: T/PR | Median Trough Plasma Concentration (Ctrough) Ratios of Atazanavir (ATZ), Ritonavir, and Tenofovir (Part B Only, Subjects on ATV-based HAART) | Ritonavir (N=9 T/PR, N=7 Pbo/PR) | 0.72 ratio (test/reference) |
| Part A: Pbo/PR | Median Trough Plasma Concentration (Ctrough) Ratios of Atazanavir (ATZ), Ritonavir, and Tenofovir (Part B Only, Subjects on ATV-based HAART) | Atazanavir (N=12 T/PR, N=6 Pbo/PR) | 1.03 ratio (test/reference) |
| Part A: Pbo/PR | Median Trough Plasma Concentration (Ctrough) Ratios of Atazanavir (ATZ), Ritonavir, and Tenofovir (Part B Only, Subjects on ATV-based HAART) | Tenofovir (N=13 T/PR, N=7 Pbo/PR) | 0.93 ratio (test/reference) |
| Part A: Pbo/PR | Median Trough Plasma Concentration (Ctrough) Ratios of Atazanavir (ATZ), Ritonavir, and Tenofovir (Part B Only, Subjects on ATV-based HAART) | Ritonavir (N=9 T/PR, N=7 Pbo/PR) | 0.74 ratio (test/reference) |
Secondary
Median Trough Plasma Concentration (Ctrough) Ratios of Efavirenz and Tenofovir (Part B Only, Subjects on EFV-based HAART)
Ctrough ratio of HAART medication with telaprevir (test) and without telaprevir (reference)
Time frame: through 12 weeks after first dose of study drug
Population: subjects with available concentration data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: T/PR | Median Trough Plasma Concentration (Ctrough) Ratios of Efavirenz and Tenofovir (Part B Only, Subjects on EFV-based HAART) | Efavirenz | 0.94 ratio (test/reference) |
| Part A: T/PR | Median Trough Plasma Concentration (Ctrough) Ratios of Efavirenz and Tenofovir (Part B Only, Subjects on EFV-based HAART) | Tenofovir | 1.06 ratio (test/reference) |
| Part A: Pbo/PR | Median Trough Plasma Concentration (Ctrough) Ratios of Efavirenz and Tenofovir (Part B Only, Subjects on EFV-based HAART) | Efavirenz | 0.79 ratio (test/reference) |
| Part A: Pbo/PR | Median Trough Plasma Concentration (Ctrough) Ratios of Efavirenz and Tenofovir (Part B Only, Subjects on EFV-based HAART) | Tenofovir | 0.64 ratio (test/reference) |
Secondary
Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12
number of subjects with undetectable HCV RNA
Time frame: 4 and 12 weeks after the first dose of study drug
Population: Subjects who were randomized and received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: T/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | Week 4 (RVR) | 5 participants |
| Part A: T/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | Weeks 4 and 12 (eRVR) | 4 participants |
| Part A: Pbo/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | Week 4 (RVR) | 0 participants |
| Part A: Pbo/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | Weeks 4 and 12 (eRVR) | 0 participants |
| Part B: EFV-based HAART + T/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | Week 4 (RVR) | 12 participants |
| Part B: EFV-based HAART + T/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | Weeks 4 and 12 (eRVR) | 12 participants |
| Part B: EFV-based HAART + Pbo/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | Week 4 (RVR) | 0 participants |
| Part B: EFV-based HAART + Pbo/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | Weeks 4 and 12 (eRVR) | 0 participants |
| Part B: ATV/R-based HAART + T/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | Week 4 (RVR) | 9 participants |
| Part B: ATV/R-based HAART + T/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | Weeks 4 and 12 (eRVR) | 7 participants |
| Part B: ATV/R-based HAART + Pbo/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | Week 4 (RVR) | 0 participants |
| Part B: ATV/R-based HAART + Pbo/PR | Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12 | Weeks 4 and 12 (eRVR) | 0 participants |
Secondary
Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment
Time frame: 12 weeks after last dose of study drug
Population: subjects who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: T/PR | Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | SVR12 | 5 participants |
| Part A: T/PR | Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | SVR24 | 5 participants |
| Part A: Pbo/PR | Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | SVR12 | 2 participants |
| Part A: Pbo/PR | Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | SVR24 | 2 participants |
| Part B: EFV-based HAART + T/PR | Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | SVR12 | 11 participants |
| Part B: EFV-based HAART + T/PR | Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | SVR24 | 11 participants |
| Part B: EFV-based HAART + Pbo/PR | Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | SVR12 | 4 participants |
| Part B: EFV-based HAART + Pbo/PR | Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | SVR24 | 4 participants |
| Part B: ATV/R-based HAART + T/PR | Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | SVR12 | 12 participants |
| Part B: ATV/R-based HAART + T/PR | Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | SVR24 | 12 participants |
| Part B: ATV/R-based HAART + Pbo/PR | Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | SVR12 | 4 participants |
| Part B: ATV/R-based HAART + Pbo/PR | Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment | SVR24 | 4 participants |