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

Phase 3

Terminated

Conditions: Hepatitis C

Interventions: Drug: Telaprevir
Drug: Ribavirin
Biological: Pegylated Interferon Alfa-2a
Drug: Highly Active Antiretroviral Therapy (HAART)

Registration Number: NCT01467479

Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 185

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
T/PR + HAART Regimen (ATV/r-Based)	Pegylated Interferon Alfa-2a	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.
T/PR + HAART Regimen (EFV-Based)	Highly Active Antiretroviral Therapy (HAART)	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.
T/PR + HAART Regimen (RAL-Based)	Pegylated Interferon Alfa-2a	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.
T/PR + HAART Regimen (RAL-Based)	Highly Active Antiretroviral Therapy (HAART)	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.
T/PR + HAART Regimen (ATV/r-Based)	Highly Active Antiretroviral Therapy (HAART)	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.
T/PR + HAART Regimen (ATV/r-Based)	Ribavirin	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.
T/PR + HAART Regimen (EFV-Based)	Pegylated Interferon Alfa-2a	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.
T/PR + HAART Regimen (ATV/r-Based)	Telaprevir	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.
T/PR + HAART Regimen (EFV-Based)	Telaprevir	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.
T/PR + HAART Regimen (EFV-Based)	Ribavirin	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.
T/PR + HAART Regimen (RAL-Based)	Telaprevir	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.
T/PR + HAART Regimen (RAL-Based)	Ribavirin	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)	12 weeks after last planned dose of study drug (up to Week 60)	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).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24)	24 weeks after last planned dose of study drug (up to Week 72)	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).
Percentage of Participants With Rapid Viral Response (RVR)	Week 4	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.
Percentage of Participants With Extended Rapid Viral Response (eRVR)	Week 4 and Week 12	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.
Percentage of Participants With Undetectable HCV RNA at End of Treatment (EOT)	EOT (up to Week 48)	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.
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to Week 52	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.
Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg)	Day -14 to Day -1 and Week 1 for ATV, EFV, and RAL; Week 1 for telaprevir	Cmax, Cmin, and Cavg were reported for atazanavir (ATV), efavirenz (EFV), raltegravir (RAL), and telaprevir.
Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region	Baseline, follow-up (Week 96)	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.

Trial Locations

Locations (40): Munchen
🇩🇪
Munchen, Germany
Florida
🇺🇸
West Palm Beach, Florida, United States
Illinois
🇺🇸
Chicago, Illinois, United States
North Carolina
🇺🇸
Durham, North Carolina, United States
Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Texas
🇺🇸
Houston, Texas, United States
Utah
🇺🇸
Salt Lake City, Utah, United States
South Carlonia
🇺🇸
Columbia, South Carolina, United States
Washington
🇺🇸
Seattle, Washington, United States
Maryland
🇺🇸
Lutherville, Maryland, United States
Hamilton
🇨🇦
Hamilton, Ontario, Canada
Vancouver
🇨🇦
Vancouver, British Columbia, Canada
Edmonton
🇨🇦
Edmonton, Alberta, Canada
Bonn
🇩🇪
Bonn, Germany
Essen
🇩🇪
Essen, Germany
Toronto
🇨🇦
Toronto, Ontario, Canada
Michigan
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Detroit, Michigan, United States
Oregon
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Portland, Oregon, United States
Connecticut
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New Haven, Connecticut, United States
DC
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Washington DC, District of Columbia, United States
New York
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Rochester, New York, United States
Barcelona
🇪🇸
Barcelona, Spain
Montreal
🇨🇦
Montreal, Quebec, Canada
Hamburg
🇩🇪
Hamburg, Germany
Georgia
🇺🇸
Decatur, Georgia, United States
Madrid
🇪🇸
Madrid, Spain
Spain
🇪🇸
Badalona, Spain
Puerto Rico
🇵🇷
San Juan, Puerto Rico
Alabama
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Birmingham, Alabama, United States
Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Massachusetts
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Springfield, Massachusetts, United States
Missouri
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Saint Louis, Missouri, United States
Washington, DC
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Washington, District of Columbia, United States
New Mexico
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Santa Fe, New Mexico, United States
Virginia
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Richmond, Virginia, United States
Maine
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Portland, Maine, United States
California
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San Francisco, California, United States
Rhode Island
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Providence, Rhode Island, United States
New Jersey
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Newark, New Jersey, United States
Ohio
🇺🇸
Cleveland, Ohio, United States