A Study to Treat Subjects With Telaprevir, Ribavirin, and Peginterferon Who Are Coinfected With HIV and Hepatitis C Virus (HCV)

Study Overview
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Brief Summary
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The purpose of this study is to treat human immunodeficiency virus (HIV) and Hepatitis C Virus (HCV) co-infected subjects with telaprevir, pegylated interferon alfa-2a (Peg-IFN-alfa-2a), and ribavirin (RBV) to achieve undetectable hepatitis C virus ribonucleic acid (HCV RNA) 12 weeks after the last planned dose of study drug.

Official Title
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An Open Label,Phase 3 Study of Telaprevir in Combination With Peginterferon Alfa 2a (Pegasys®) and Ribavirin (Copegus®) in Subjects Coinfected With Genotype 1 Hepatitis C Virus and Human Immunodeficiency Virus Type 1(HCV/HIV-1)

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Telaprevir
* Drug: Ribavirin
* Biological: Pegylated Interferon Alfa-2a
* Drug: Highly Active Antiretroviral Therapy (HAART)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have chronic, genotype 1a or 1b, hepatitis C with HCV RNA greater than (>) 1000 international units per milliliter (IU/mL) Population A: HCV Pegylated interferon (Peg-IFN)/RBV treatment naive (received no prior HCV therapy)or Peg-IFN/RBV prior treatment with relapse Population B: Peg-IFN/RBV prior null or partial responder Participants must not have achieved undetectable HCV RNA 24 weeks after the last planned dose of study drug (SVR24) after at least 1 prior course of Peg IFN/RBV therapy of standard duration Participant must have positive HIV antibody at Screening Participant must have a diagnosis of HIV-1 infection >6 months before Screening Participants should be taking 1 of the following permissible highly active antiretroviral therapy (HAART) regimens for HIV continuously for 12 weeks prior to screening: Atripla® or equivalent components (efavirenz, tenofovir, emtricitabine) Efavirenz plus Epzicom® (abacavir, lamivudine) or equivalent components Boosted atazanavir (atazanavir with ritonavir) plus Truvada® (tenofovir, emtricitabine) or equivalent components Boosted atazanavir plus Epzicom®, or equivalent components Raltegravir plus Truvada®, or equivalent components Raltegravir plus Epzicom®, or equivalent components Cluster of differentiation 4 (CD4) counts and human immunodeficiency virus Type 1 (HIV-1) ribonucleic acid (RNA) meeting acceptable criteria at Screening as specified in the protocol Laboratory values within acceptable ranges at Screening as specified in the protocol Exclusion Criteria: Subjects anticipating a need to switch HAART regimens within 14 weeks after Day 1 or any switches occurring 12 weeks prior to Day 1 Use of azidothymidine (AZT), didanosine (ddI) or stavudine (d4T) nucleosides Contraindications to any planned HAART component as per the respective drug labeling information Contraindications to Peg-IFN or RBV Evidence of hepatic decompensation Clinical suspicion of acute hepatitis Any other cause of liver disease in addition to hepatitis C History of organ transplantation (except cornea and skin) Autoimmune-mediated disease Participated in any investigational drug study within 90 days before Day 1 Previous treatment with an HCV protease inhibitor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T/PR + HAART Regimen (ATV/r-Based)<br>Participants who were receiving atazanavir/ritonavir (ATV/r) based highly active antiretroviral therapy (HAART) at baseline, received Telaprevir (T)1125 milligram (mg) tablet twice daily for 12 weeks in combination with pegylated interferon alfa 2a (P) (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (R) (RBV) tablet orally twice daily at a dose of 800 milligram per day (mg/day) for 24 or 48 weeks, depending on individual response to telaprevir treatment. Participants continued their HAART, as per standard practice and investigator discretion. | Drug: Telaprevir<br>* Tablet<br>* Other names: VX-950;Drug: Ribavirin<br>* Tablet<br>* Other names: RBV;Biological: Pegylated Interferon Alfa-2a<br>* Subcutaneous Injection<br>* Other names: Peg-IFN-Alfa-2a;Drug: Highly Active Antiretroviral Therapy (HAART)<br>* Atazanavir/ritonavir (ATV/r) based HAART, Efavirenz (EFV) based HAART, or Raltegravir (RAL) based HAART, as per standard practice. HAART medications were not considered study drugs.<br>|
| Experimental: T/PR + HAART Regimen (EFV-Based)<br>Participants who were receiving efavirenz (EFV) based highly active antiretroviral therapy (HAART) at baseline, received Telaprevir (T)1125 milligram (mg) tablet three times a day for 12 weeks in combination with pegylated interferon alfa 2a (P) (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (R) (RBV) tablet orally twice daily at a dose of 800 milligram per day (mg/day) for 24 or 48 weeks, depending on individual response to telaprevir treatment. Participants continued their HAART, as per standard practice and investigator discretion. | Drug: Telaprevir<br>* Tablet<br>* Other names: VX-950;Drug: Ribavirin<br>* Tablet<br>* Other names: RBV;Biological: Pegylated Interferon Alfa-2a<br>* Subcutaneous Injection<br>* Other names: Peg-IFN-Alfa-2a;Drug: Highly Active Antiretroviral Therapy (HAART)<br>* Atazanavir/ritonavir (ATV/r) based HAART, Efavirenz (EFV) based HAART, or Raltegravir (RAL) based HAART, as per standard practice. HAART medications were not considered study drugs.<br>|
| Experimental: T/PR + HAART Regimen (RAL-Based)<br>Participants who were receiving raltegravir (RAL) based highly active antiretroviral therapy (HAART) at baseline, received Telaprevir (T)1125 milligram (mg) tablet twice daily for 12 weeks in combination with pegylated interferon alfa 2a (P) (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (R) (RBV) tablet orally twice daily at a dose of 800 milligram per day (mg/day) for 24 or 48 weeks, depending on individual response to telaprevir treatment. Participants continued their HAART, as per standard practice and investigator discretion. | Drug: Telaprevir<br>* Tablet<br>* Other names: VX-950;Drug: Ribavirin<br>* Tablet<br>* Other names: RBV;Biological: Pegylated Interferon Alfa-2a<br>* Subcutaneous Injection<br>* Other names: Peg-IFN-Alfa-2a;Drug: Highly Active Antiretroviral Therapy (HAART)<br>* Atazanavir/ritonavir (ATV/r) based HAART, Efavirenz (EFV) based HAART, or Raltegravir (RAL) based HAART, as per standard practice. HAART medications were not considered study drugs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | SVR 12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (<lower limit of quantification) at 12 weeks after last planned dose of study drug. The plasma hepatitis C virus ribonucleic acid (HCV RNA) level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL). | 12 weeks after last planned dose of study drug (up to Week 60) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | SVR 24 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (<lower limit of quantification) at 24 weeks after last planned dose of study drug. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL). | 24 weeks after last planned dose of study drug (up to Week 72) | 
| Percentage of Participants With Rapid Viral Response (RVR) | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. RVR was defined as undetectable HCV RNA (<lower limit of quantification) 4 weeks after the start of study treatment. | Week 4 | 
| Percentage of Participants With Extended Rapid Viral Response (eRVR) | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. eRVR was defined as undetectable HCV RNA (<lower limit of quantification) at both 4 weeks and 12 weeks after the start of study treatment. | Week 4 and Week 12 | 
| Percentage of Participants With Undetectable HCV RNA at End of Treatment (EOT) | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. Percentage of participants with undetectable HCV RNA (<lower limit of quantification) at EOT (up to Week 48) are reported. Data for this outcome was not planned to be reported by prior response. | EOT (up to Week 48) | 
| Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. SAE (subset of AE): 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. | Up to Week 52 | 
| Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | Cmax, Cmin, and Cavg were reported for atazanavir (ATV), efavirenz (EFV), raltegravir (RAL), and telaprevir. | Day -14 to Day -1 and Week 1 for ATV, EFV, and RAL; Week 1 for telaprevir | 
| Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region | Sequence analysis of the HCV NS3-4A region was performed to monitor telaprevir-resistant variants. HCV RNA was isolated from the plasma, amplified by reverse transcription-polymerase chain reaction (RT-PCR), and sequenced (sequencing assay limit of detection HCV RNA >=1000 IU/mL). Results of this outcome measure were to be reported for overall participants instead of by HAART treatment. | Baseline, follow-up (Week 96) |