Trial record 10 of 27 for:    " November 16, 2011":" December 16, 2011"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01482767
First received: November 28, 2011
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

Hepatitis C virus (HCV) infection is a leading cause of death and illness in people with HIV-1. Currently, the standard treatment for people with HIV-1 and HCV coinfection includes two drugs—pegylated-interferon alfa 2b (PEG-IFN) and ribavirin (RBV). The purpose of this study is to evaluate the effectiveness of giving boceprevir (BOC) together with standard treatment in treating HCV infection in people with HIV-1 and HCV coinfection.


Condition Intervention Phase
HIV Infections
Hepatitis C
Drug: Pegylated-Interferon Alfa 2b (PEG-IFN)
Drug: Ribavirin (RBV)
Drug: Boceprevir (BOC)
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Phase III, Open-Label Study of Boceprevir, Pegylated-Interferon Alfa 2b and Ribavirin in HCV/HIV Coinfected Subjects

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Sustained Virological Response (SVR) defined as undetectable HCV RNA [ Time Frame: Measured at 24 weeks after treatment discontinuation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Grade 3 or higher signs and symptoms and laboratory abnormalities and other serious adverse events (AEs) during the study [ Time Frame: Measured through Week 72 ] [ Designated as safety issue: Yes ]
  • Undetectable HCV RNA discontinuation (SVR12) [ Time Frame: Measured at Weeks 4, 8, 12, and at 12 weeks after treatment discontinuation ] [ Designated as safety issue: No ]
  • Baseline HIV-1 viral load and changes from baseline at each post-entry visit [ Time Frame: Measured through Week 72 ] [ Designated as safety issue: No ]
  • Baseline CD4+ T-cell count and changes from baseline at each post-entry visit [ Time Frame: Measured through Week 72 ] [ Designated as safety issue: No ]
  • Baseline fibrosis stage, race, gender, insulin sensitivity, and HCV viral load level [ Time Frame: Measured at baseline ] [ Designated as safety issue: No ]
  • Undetectable HCV RNA [ Time Frame: Measured at Weeks 16, 20, 24, and 28 ] [ Designated as safety issue: No ]
  • Grade 2 or higher signs and symptoms and laboratory abnormalities and other serious AEs [ Time Frame: Measured at Week 28 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 310
Study Start Date: April 2012
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HCV Treatment-Naive (Group A)
Group A will include HCV treatment-naive participants who have never received treatment with PEG-IFN, or experimental agents used to treat HCV, with or without RBV. Participants will receive PEG-IFN and RBV followed by triple therapy with PEG-IFN, RBV, and BOC until Week 36 or until the end of the study treatment duration (Week 48). Participants who stop triple therapy at Week 36 will receive an additional 12 weeks of PEG-IFN and RBV (until Week 48). Some participants will discontinue study treatment at Week 28.
Drug: Pegylated-Interferon Alfa 2b (PEG-IFN)
Week 1 through Week 48: 1.5 mcg/kg SC once a week (based on participant's weight at entry).
Drug: Ribavirin (RBV)
Week 1 through Week 48: 800-1400 mg orally per day with food (based on participant's weight at entry).
Drug: Boceprevir (BOC)
Participants will receive 800 mg orally every 8 hours with food at Week 5 through Week 36 or through Week 48.
Experimental: HCV Treatment-Experienced (Group B)
Group B will include participants who have received any treatment with standard interferon or PEG-IFN with or without RBV, provided the last dose of treatment was 90 days or more before study entry. Participants will receive PEG-IFN and RBV followed by triple therapy with PEG-IFN, RBV, and BOC until Week 36 or until the end of the study treatment duration (Week 48). Participants who stop triple therapy at Week 36 will receive an additional 12 weeks PEG-IFN and RBV (until Week 48).
Drug: Pegylated-Interferon Alfa 2b (PEG-IFN)
Week 1 through Week 48: 1.5 mcg/kg SC once a week (based on participant's weight at entry).
Drug: Ribavirin (RBV)
Week 1 through Week 48: 800-1400 mg orally per day with food (based on participant's weight at entry).
Drug: Boceprevir (BOC)
Participants will receive 800 mg orally every 8 hours with food at Week 5 through Week 36 or through Week 48.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (Groups A and B):

  • Men and women 18 years of age or older
  • Presence of chronic HCV infection, defined by presence of plasma or serum HCV RNA in a participant with HCV antibody for at least 180 days, two documented HCV RNA positive results greater than 180 days apart, or positive HCV RNA with biopsy demonstrating chronic hepatitis. More information on this criterion can be found in the protocol.
  • Serum or plasma HCV RNA level 10,000 IU/mL or greater obtained within 42 days prior to study entry by any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent. NOTE: This must be a quantitative HCV RNA test, not a qualitative HCV RNA test.
  • Screening HCV genotype 1 performed within 6 months prior to study entry from a College of American Pathologists (CAP)/CLIA-approved laboratory. Screening genotype test MUST BE performed locally; ONLY IF IT IS NOT AVAILABLE LOCALLY can it be done at the designated virology specialty laboratory (VSL) (see A5294 Laboratory Processing Chart [LPC] in protocol).
  • Liver biopsy or HCV FibroSURE™ test within 104 weeks prior to study entry with interpretation consistent with chronic HCV infection. If a liver biopsy HCV FibroSURE™ test has not been performed within 104 weeks prior to study entry, then either a biopsy or HCV FibroSURE™ test must be obtained prior to enrollment. The cut-off value for the FibroSURE™ test is 0.74, where greater than 0.74 is interpreted as cirrhosis. More information on this criterion can be found in the protocol.
  • Participants should have alpha feto protein (AFP) levels less than 50. If 50 or greater, they should have a liver imaging study (e.g., ultrasound, computed tomography [CT] scan, magnetic resonance imaging [MRI] showing no evidence of hepatocellular carcinoma.
  • HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, by HIV-1 p24 antigen, or by plasma HIV-1 RNA viral load. More information on this criterion can be found in the protocol.
  • Currently not on any antiretroviral therapy (ART) for at least 4 weeks immediately prior to entry or on stable ART for at least 8 weeks prior to study entry using a dual NRTI backbone PLUS one of the following: EFV, RAL, LPV/RTV 400/100 mg twice daily, ATV/RTV, DRV/RTV 600/100 mg twice daily. Breaks in therapy for a maximum of 14 days will be allowed. Dose modifications or changes in drugs during the 8 weeks prior to study entry are permitted unless the change in drug was due to treatment failure. Participants not on ART should have no plans to initiate therapy during the first 24 weeks after study entry. Participants on ART should plan to remain on the same therapy for at least 12 weeks after study entry. More information on this criterion can be found in the protocol.
  • CD4+ T-cell count greater than 200 cells/mm^3 obtained within 42 days prior to study entry at any laboratory that has a CLIA certification or its equivalent
  • For participants on ART, screening plasma HIV-1 RNA less than 50 copies/mL obtained within 42 days prior to study entry by any Food and Drug Administration (FDA)-approved test for quantifying HIV-1 RNA at any laboratory that has a CLIA certification or its equivalent. For participants who are not on ART, plasma HIV-1 RNA less than 50,000 copies/mL obtained within 42 days prior to study entry by any FDA-approved test for quantifying HIV-1 RNA at any laboratory that has a CLIA certification or its equivalent.
  • The following laboratory values must be obtained within 42 days prior to entry:

    • Absolute neutrophil count (ANC) 1000/mm^3 or greater
    • Hemoglobin greater than 12 g/dL for men and greater than 11 g/dL for women
    • Platelet count greater than 80,000 per mm3
    • Creatinine less than 1.5 mg/dL
    • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alkaline phosphatase (ALT)/serum glutamic pyruvic transaminaseless (SGPT) less than or equal to 10 x the upper limit of normal (ULN)
    • Direct bilirubin less than 1.5 mg/dL
    • International normalized ratio (INR) less than 1.5
    • Serum lipase less than or equal to 1.5 x ULN
    • Thyroid stimulating hormone (TSH) within normal range, unless accompanied by thyroid profile consistent with normal thyroid function
  • Female participants of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL performed within 42 days prior to study entry
  • All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization)
  • When participating in sexual activity that could lead to pregnancy, participants must agree to use at least two reliable methods of contraception simultaneously while receiving protocol-specified medications, and for 6 months after stopping the medications. Such methods include:

    • Condoms (male or female) with a spermicidal agent
    • Diaphragm or cervical cap with spermicide
    • Intrauterine device (IUD)
    • Tubal ligation More information on this criterion can be found in the protocol.
  • Participants who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy or men who have documented azoospermia or have undergone vasectomy) are eligible without requiring the use of contraceptives. Acceptable documentation of sterilization and menopause is detailed in protocol.
  • Ability and willingness of participant to provide written informed consent

Step 2 Inclusion Criterion (Group A):

Completion of Step 1.

Exclusion Criteria (Groups A and B):

  • Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation
  • Evidence of decompensated liver disease manifested by the presence of or history of ascites, variceal bleeding, or hepatic encephalopathy. If hepatic cirrhosis is determined by liver biopsy (Stage 4 Metavir or Stage 5, 6 Ishak) or by imaging, then participants must be no more than Child-Pugh Class A and have a Child-Pugh-Turcotte (CPT) score of 6 or less. More information on this criterion can be found in the protocol.
  • Other known causes of significant liver disease including chronic or acute hepatitis B, acute hepatitis A, hemochromatosis, or homozygote alpha-1 antitrypsin deficiency
  • Infection with any HCV genotype other than genotype 1, or mixed genotype infection
  • Uncontrolled or active depression or other psychiatric disorder such as untreated Grade 3 psychiatric disorder or Grade 3 disorder not amenable to medical intervention that in the opinion of the site investigator might preclude tolerability or safety of study requirements. Individuals with suicidal ideation or history of a suicidal attempt in the last 5 years prior to enrollment will be excluded.
  • History of uncontrolled seizure disorders
  • Serious illness including malignancy, active coronary artery disease within 24 weeks prior to study entry, or other chronic medical conditions that in the opinion of the site investigator may preclude completion of the protocol. Such conditions may be discussed with the study chairs.
  • Presence of active or acute AIDS-defining opportunistic infections within 12 weeks prior to study entry. More information on this criterion can be found in the protocol.
  • History of hemoglobinopathy (e.g., thalassemia) or any other cause of or tendency to hemolysis
  • History of major organ transplantation with an existing functional graft
  • History of autoimmune processes including Crohn's disease, ulcerative colitis, severe psoriasis, or rheumatoid arthritis that may be exacerbated by IFN use.
  • Breastfeeding
  • Male participants with pregnant sexual partner
  • Use of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 14 days prior to study entry
  • Use of systemic corticosteroids, lovastatin, simvastatin, interferon gamma, tumor necrosis factor(TNF)-alpha inhibitors, rifampin, rifabutin, pyrazinamide, isoniazid, ganciclovir or hydroxyurea within 14 days prior to study entry
  • Previous use of any HCV protease or polymerase inhibitor
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Serious illness requiring systemic treatment and/or hospitalization within 42 days prior to entry

Step 2 Exclusion Criterion (Group A):

  • Virologic failure as defined in protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01482767

  Show 43 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Adeel A Butt, MD, MS University of Pittsburgh
Study Chair: Kenneth E Sherman, MD, PhD University of Cincinnati CRS
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01482767     History of Changes
Other Study ID Numbers: A5294 (BIRTH), 11774, ACTG 5294, BIRTH
Study First Received: November 28, 2011
Last Updated: June 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Hepatitis
Hepatitis A
Hepatitis C
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
Flaviviridae Infections
Interferon-alpha
Interferon Alfa-2a
Interferon Alfa-2b
Interferons
Ribavirin
Peginterferon alfa-2b
Reaferon
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014