Evaluating the Effectiveness of Boceprevir, Pegylated-Interferon Alfa 2b and Ribavirin in Treating Hepatitis C Virus (HCV) Infection in Adults With HIV and HCV Infection
- Conditions
- Hepatitis CHIV Infections
- Interventions
- Registration Number
- NCT01482767
- Brief Summary
Hepatitis C virus (HCV) infection is a leading cause of death and illness in people with HIV-1. At the time the study was designed, the standard treatment for people with HIV-1 and HCV coinfection included two drugs: pegylated-interferon alfa 2b (PEG-IFN) and ribavirin (RBV). The purpose of this study was to evaluate the effectiveness of giving boceprevir (BOC) together with standard treatment in treating HCV infection in people with HIV-1 and HCV coinfection.
- Detailed Description
For HIV-1-infected individuals, HCV infection is a leading cause of morbidity and mortality, and the prevalence of HCV infection is higher among those infected with HIV-1. At the time the study was designed, the standard-of-care (SOC) therapy for HCV infection was treatment with both PEG-IFN and RBV. This therapy is 40%-45% effective in patients with HCV infection but is significantly less effective in patients with both HCV and HIV-1 (Shire et al. J Viral Hepat., 2007). The purpose of this study was to evaluate the effectiveness of adding BOC (Kwo et al. Lancet, 2010), an HCV protease inhibitor, to SOC therapy in treating HCV infection (genotype 1) in HCV/HIV-1-coinfected adults.
Participants were enrolled into one of two groups based on previous HCV treatment experience.
1. Group A: HCV treatment-naive participants who had never received treatment with PEG-IFN or experimental agents used to treat HCV, with or without RBV (N=170, refer to the note below).
2. Group B: HCV treatment-experienced participants who had received any treatment with standard interferon or with PEG-IFN with or without RBV, provided the last dose of treatment was 90 days or more before study entry (N=140, refer to the note below).
Note: The team correspondence with the FDA led to an amendment to close enrollment in December 2013, prior to the target sample sizes of 170 in Group A and 140 in Group B, as the study power could be lowered while still meeting the key study objectives.
All participants had to be on stable antiretroviral therapy (ART) for at least 8 weeks prior to study entry using a dual nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone plus one of the following: efavirenz (EFV), raltegravir (RAL), lopinavir (LPV)/ritonavir (RTV) 400/100 mg twice daily, atazanavir (ATV)/RTV, darunavir (DRV)/RTV 600/100 mg twice daily OR must not have received any ART for at least 4 weeks immediately prior to entry. Participation in this study lasted approximately 72 weeks.
HCV treatment-naive participants (Group A) were treated with PEG-IFN and RBV for 4 weeks (lead-in). Then BOC was added to the treatment regimen (triple therapy). Cirrhotic participants received 44 weeks of triple therapy. Among non-cirrhotics, the Week 8 HCV RNA was used to determine total duration of therapy. Those who had undetectable HCV RNA at Week 8 completed therapy at Week 28. Those with detectable HCV RNA at Week 8 received 32 weeks of triple therapy followed by 12 additional weeks of double-drug therapy with PEG-IFN/RBV. HCV treatment-experienced participants (Group B) also had a lead-in followed by 32 weeks of triple therapy and 12 weeks of PEG-IFN/RBV double therapy if non-cirrhotic, or by 44 weeks of triple therapy if cirrhotic.
Treatment was to be discontinued due to HCV virologic failure if:
1. HCV RNA ≥100 IU/mL at Week 12,
2. detectable HCV RNA at Week 24, or
3. confirmed HCV RNA \>1000 IU/mL any time after Week 12.
Undetectable HCV RNA was defined as below the lower limit of quantification (LLOQ) and target not detected (TND) by Roche COBAS® TaqMan® HCV Test v2.0.
Study visits were scheduled at screening and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24 and 28 for both study groups. Group A participants who completed treatment at Week 28 had further study visits at Weeks 40, 52, 60, and 72. Participants who were prescribed 48-weeks of therapy (Group A and Group B) had further study visits at Weeks 32, 36, 40, 44, 48, 60, and 72. At each visit, a physical examination and blood collection were conducted. Participants also completed an HCV treatment adherence questionnaire. Select visits included urine collection and pregnancy testing (for women of reproductive potential). Plasma, serum, and peripheral blood mononuclear cells (PBMCs) were be stored for use in future studies. After experiencing HCV virologic failure as defined above or premature treatment discontinuation due to safety or other reasons, participants were followed on a separate schedule of events with visits every 12 weeks from Week 24 to 72. The evaluations at these follow-up visits were limited to safety evaluations and stored plasma/serum sample collection.
The A5294 study consisted of single-arm evaluations to assess the efficacy of BOC added to PEG-IFN/RBV in the two study populations:
1. HCV treatment-naive participants (Group A)
2. HCV treatment-experienced participants (Group B).
The two study populations were addressed together in this single trial - rather than in two separate trials - mainly for administrative efficiency. The analyses were conducted separately for each Study Group. The study was not designed for comparison. The pooled summaries for Baseline Characteristics provided in the Results Section in this record were prepared solely for the ClinicalTrials.gov results submission.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 262
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description HCV Treatment-Naive (Group A) Ribavirin (RBV) Participants were prescribed a lead-in with PEG-IFN and RBV for 4 weeks. After the lead-in, BOC was added. Cirrhotic participants received 44 weeks of triple therapy (BOC+PEG-IFN+RBV). Among non-cirrhotics, the Week 8 HCV RNA was used to determine total duration of therapy. Those who had undetectable HCV RNA at Week 8 completed therapy at Week 28. Those with detectable HCV RNA at Week 8 received 32 weeks of triple therapy followed by 12 additional weeks of PEG-IFN+RBV. HCV Treatment-Experienced (Group B) Ribavirin (RBV) Participants were prescribed a lead-in with PEG-IFN and RBV for 4 weeks. After the lead-in, BOC was added. Cirrhotic participants received 44 weeks of triple therapy (BOC+PEG-IFN+RBV), and non-cirrhotics received 32 weeks of triple therapy followed by 12 additional weeks of PEG-IFN+RBV. HCV Treatment-Naive (Group A) Pegylated-Interferon Alfa 2b (PEG-IFN) Participants were prescribed a lead-in with PEG-IFN and RBV for 4 weeks. After the lead-in, BOC was added. Cirrhotic participants received 44 weeks of triple therapy (BOC+PEG-IFN+RBV). Among non-cirrhotics, the Week 8 HCV RNA was used to determine total duration of therapy. Those who had undetectable HCV RNA at Week 8 completed therapy at Week 28. Those with detectable HCV RNA at Week 8 received 32 weeks of triple therapy followed by 12 additional weeks of PEG-IFN+RBV. HCV Treatment-Experienced (Group B) Pegylated-Interferon Alfa 2b (PEG-IFN) Participants were prescribed a lead-in with PEG-IFN and RBV for 4 weeks. After the lead-in, BOC was added. Cirrhotic participants received 44 weeks of triple therapy (BOC+PEG-IFN+RBV), and non-cirrhotics received 32 weeks of triple therapy followed by 12 additional weeks of PEG-IFN+RBV. HCV Treatment-Experienced (Group B) Boceprevir (BOC) Participants were prescribed a lead-in with PEG-IFN and RBV for 4 weeks. After the lead-in, BOC was added. Cirrhotic participants received 44 weeks of triple therapy (BOC+PEG-IFN+RBV), and non-cirrhotics received 32 weeks of triple therapy followed by 12 additional weeks of PEG-IFN+RBV. HCV Treatment-Naive (Group A) Boceprevir (BOC) Participants were prescribed a lead-in with PEG-IFN and RBV for 4 weeks. After the lead-in, BOC was added. Cirrhotic participants received 44 weeks of triple therapy (BOC+PEG-IFN+RBV). Among non-cirrhotics, the Week 8 HCV RNA was used to determine total duration of therapy. Those who had undetectable HCV RNA at Week 8 completed therapy at Week 28. Those with detectable HCV RNA at Week 8 received 32 weeks of triple therapy followed by 12 additional weeks of PEG-IFN+RBV.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Sustained Virologic Response at 24 Weeks After Treatment Discontinuation (SVR24) 24 weeks after treatment discontinuation SVR24 was defined as undetectable HCV RNA (below the lower limit of quantitation of the assay and target not detected by Roche COBAS® TaqMan® HCV Test v2.0) at 24 weeks after treatment discontinuation. Participants without HCV RNA for SVR24 determination were considered not to have achieved SVR24.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With HIV-1 Viral Load <50 Copies/mL Entry and weeks (W) 4, 8, 12, 24, 28, 40, 48, 52, 60, 72 HIV-1 RNA testing was performed with Abbott RealTime HIV-1 assay (LLOQ=40 copies/mL) or with Roche COBAS AmpliPrep/Taqman HIV-1 assay (LLOQ=20 copies/mL).
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) From study treatment dispensation to Week 72 Number of participants who experienced an AE (sign or symptom or laboratory abnormality) of Grade 3 or higher at any time after baseline while on study. The AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening.
CD4+ T-Cell Count (CD4) Change From Baseline Entry and weeks (W) 8, 12, 24, 28, 40, 48, 52, 60, 72 Change in CD4 T-cell count was calculated as value at the post entry visit minus the value at entry.
Number of Participants With Undetectable HCV RNA at Week 4, 8 and 12 Study Visits Weeks (W) 4, 8, 12 Undetectable HCV RNA was defined as below the lower limit of quantitation of the assay and target not detected by Roche COBAS® TaqMan® HCV Test v2.0.
Number of Participants With Grade 2 or Higher Signs and Symptoms and Laboratory Abnormalities and Other Serious AEs From study treatment dispensation to Week 28 This outcome measure was intended for a potential interim analysis when study data up to Week 28 were complete. However, this interim analysis was not conducted. Refer to Outcome Measure 2 above for the safety outcome that includes the whole study duration from entry to week 72.
Percentage of Participants With Sustained Virologic Response at 12 Weeks After Treatment Discontinuation (SVR12) 12 weeks after treatment discontinuation SVR12 was defined as undetectable HCV RNA (below the lower limit of quantitation of the assay and target not detected by Roche COBAS® TaqMan® HCV Test v2.0) at 12 weeks after treatment discontinuation. Participants without HCV RNA for SVR12 determination were considered not to have achieved SVR12.
Number of Participants With Undetectable HCV RNA at Week 16, 20, 24 and 28 Study Visits Weeks (W) 16, 20, 24, and 28 Undetectable HCV RNA was defined as below the lower limit of quantitation of the assay and target not detected by Roche COBAS® TaqMan® HCV Test v2.0. This outcome measure was intended for a potential interim analysis when study data up to Week 28 were complete. However, this interim analysis was not conducted.
Trial Locations
- Locations (43)
Rush University CRS
🇺🇸Chicago, Illinois, United States
Case Clinical Research Site
🇺🇸Cleveland, Ohio, United States
MetroHealth CRS
🇺🇸Cleveland, Ohio, United States
University of Southern California CRS
🇺🇸Los Angeles, California, United States
UCLA CARE Center CRS
🇺🇸Los Angeles, California, United States
Harbor-UCLA CRS
🇺🇸Torrance, California, United States
Northwestern University CRS
🇺🇸Chicago, Illinois, United States
IHV Baltimore Treatment CRS
🇺🇸Baltimore, Maryland, United States
Johns Hopkins University CRS
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital CRS (MGH CRS)
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
🇺🇸Boston, Massachusetts, United States
Bmc Actg Crs
🇺🇸Boston, Massachusetts, United States
Ohio State University CRS
🇺🇸Columbus, Ohio, United States
Penn Therapeutics, CRS
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh CRS
🇺🇸Pittsburgh, Pennsylvania, United States
Trinity Health and Wellness Center CRS
🇺🇸Dallas, Texas, United States
Houston AIDS Research Team CRS
🇺🇸Houston, Texas, United States
University of Washington AIDS CRS
🇺🇸Seattle, Washington, United States
UCSD Antiviral Research Center CRS
🇺🇸San Diego, California, United States
Cincinnati Clinical Research Site
🇺🇸Cincinnati, Ohio, United States
Ucsf Hiv/Aids Crs
🇺🇸San Francisco, California, United States
Duke Univ. Med. Ctr. Adult CRS
🇺🇸Durham, North Carolina, United States
Vanderbilt Therapeutics (VT) CRS
🇺🇸Nashville, Tennessee, United States
Cooper Univ. Hosp. CRS
🇺🇸Camden, New Jersey, United States
New Jersey Medical School Clinical Research Center CRS
🇺🇸Newark, New Jersey, United States
Georgetown University CRS (GU CRS)
🇺🇸Washington, District of Columbia, United States
Wayne State Univ. CRS
🇺🇸Detroit, Michigan, United States
Henry Ford Hosp. CRS
🇺🇸Detroit, Michigan, United States
Stanford AIDS Clinical Trials Unit CRS
🇺🇸Palo Alto, California, United States
The Ponce de Leon Center CRS
🇺🇸Atlanta, Georgia, United States
Washington University Therapeutics (WT) CRS
🇺🇸Saint Louis, Missouri, United States
Weill Cornell Chelsea CRS
🇺🇸New York, New York, United States
Bronx-Lebanon Hosp. Ctr. CRS
🇺🇸Bronx, New York, United States
Weill Cornell Uptown CRS
🇺🇸New York, New York, United States
Columbia P&S CRS
🇺🇸New York, New York, United States
University of Rochester Adult HIV Therapeutic Strategies Network CRS
🇺🇸Rochester, New York, United States
The Miriam Hospital Clinical Research Site (TMH CRS) CRS
🇺🇸Providence, Rhode Island, United States
Puerto Rico AIDS Clinical Trials Unit CRS
🇵🇷San Juan, Puerto Rico
Alabama CRS
🇺🇸Birmingham, Alabama, United States
University of Colorado Hospital CRS
🇺🇸Aurora, Colorado, United States
Denver Public Health CRS
🇺🇸Denver, Colorado, United States
Chapel Hill CRS
🇺🇸Chapel Hill, North Carolina, United States
Virginia Commonwealth University CRS
🇺🇸Richmond, Virginia, United States