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

NCT01482767 | Completed Phase 3 Results DMC

• 4 other identifiers: A5294 (BIRTH)11774ACTG 5294BIRTH
• Study Type: interventional
• Target: 262
• Locations: 2 countries
• Sites: 43

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.

Conditions

HIV Infections; Hepatitis C

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Sustained Virologic Response at 24 Weeks After Treatment Discontinuation (SVR24)

  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.

  24 weeks after treatment discontinuation

Secondary Outcomes (7)

• Percentage of Participants With Grade 3 or Higher Adverse Events (AEs)

  From study treatment dispensation to Week 72

• Percentage of Participants With Sustained Virologic Response at 12 Weeks After Treatment Discontinuation (SVR12)

  12 weeks after treatment discontinuation

• 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

• CD4+ T-Cell Count (CD4) Change From Baseline

  Entry and weeks (W) 8, 12, 24, 28, 40, 48, 52, 60, 72

• Number of Participants With Undetectable HCV RNA at Week 4, 8 and 12 Study Visits

  Weeks (W) 4, 8, 12

Study Arms (2)

HCV Treatment-Naive (Group A)

EXPERIMENTAL

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.

Drug: Pegylated-Interferon Alfa 2b (PEG-IFN); Drug: Ribavirin (RBV); Drug: Boceprevir (BOC)

HCV Treatment-Experienced (Group B)

EXPERIMENTAL

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.

Drug: Pegylated-Interferon Alfa 2b (PEG-IFN); Drug: Ribavirin (RBV); Drug: Boceprevir (BOC)

Interventions

Pegylated-Interferon Alfa 2b (PEG-IFN) DRUG

1.5 mcg/kg subcutaneously (SC) once a week (based on participant's weight at entry) for up to 48 weeks depending on cirrhosis status and, in Group A, Week 8 HCV viral response.

HCV Treatment-Experienced (Group B); HCV Treatment-Naive (Group A)

Ribavirin (RBV) DRUG

800-1400 mg orally per day with food (based on participant's weight at entry) for up to 48 weeks depending on cirrhosis status and, in Group A, Week 8 HCV viral response.

HCV Treatment-Experienced (Group B); HCV Treatment-Naive (Group A)

Boceprevir (BOC) DRUG

800 mg orally every 8 hours with food from Week 5 to up to Week 48 depending on cirrhosis status and, in Group A, Week 8 HCV viral response

HCV Treatment-Experienced (Group B); HCV Treatment-Naive (Group A)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Screening HCV genotype 1 performed within 6 months prior to study entry.
• 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 had not been performed within 104 weeks prior to study entry, then either a biopsy or HCV FibroSURE™ test must have been obtained prior to enrollment. The cut-off value for the FibroSURE™ test was 0.74, where greater than 0.74 was interpreted as cirrhosis. More information on this criterion can be found in the protocol.
• Alpha feto protein (AFP) levels less than 50. If 50 or greater, they must have had a liver imaging study (e.g., ultrasound, computed tomography \[CT\] scan, magnetic resonance imaging \[MRI\] showing no evidence of hepatocellular carcinoma.
• HIV-1 infection. 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 were allowed. Dose modifications or changes in drugs during the 8 weeks prior to study entry were permitted unless the change in drug was due to treatment failure. 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.
• For participants on ART, screening plasma HIV-1 RNA less than 50 copies/mL obtained within 42 days prior to study entry. For participants not on ART, plasma HIV-1 RNA less than 50,000 copies/mL obtained within 42 days prior to study entry.
• The following laboratory values 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 mm\^3,
• Creatinine less than 1.5 mg/dL,

You may not qualify if:

• 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 was determined by liver biopsy (Stage 4 Metavir or Stage 5, 6 Ishak) or by imaging, then participants had to 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 have precluded tolerability or safety of study requirements. Individuals with suicidal ideation or history of a suicidal attempt in the last 5 years prior to enrollment were 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 have precluded completion of the protocol.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (43)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

University of Southern California CRS

Los Angeles, California, 90033-1079, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Stanford AIDS Clinical Trials Unit CRS

Palo Alto, California, 94304-5350, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

Harbor-UCLA CRS

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Denver Public Health CRS

Denver, Colorado, 80204, United States

Location

Georgetown University CRS (GU CRS)

Washington D.C., District of Columbia, 20007, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Rush University CRS

Chicago, Illinois, 60612, United States

Location

IHV Baltimore Treatment CRS

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS

Boston, Massachusetts, 02115, United States

Location

Bmc Actg Crs

Boston, Massachusetts, 02118, United States

Location

Wayne State Univ. CRS

Detroit, Michigan, 48201, United States

Location

Henry Ford Hosp. CRS

Detroit, Michigan, 48202, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

Location

Cooper Univ. Hosp. CRS

Camden, New Jersey, 08103, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10011, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

Weill Cornell Uptown CRS

New York, New York, 10065, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, 14642, United States

Location

Bronx-Lebanon Hosp. Ctr. CRS

The Bronx, New York, 10457, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, 27710, United States

Location

Cincinnati Clinical Research Site

Cincinnati, Ohio, 45219, United States

Location

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

MetroHealth CRS

Cleveland, Ohio, 44109, United States

Location

Ohio State University CRS

Columbus, Ohio, 43210, United States

Location

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

The Miriam Hospital Clinical Research Site (TMH CRS) CRS

Providence, Rhode Island, 02906, United States

Location

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

Location

Trinity Health and Wellness Center CRS

Dallas, Texas, 75208, United States

Location

Houston AIDS Research Team CRS

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University CRS

Richmond, Virginia, 23298, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104-9929, United States

Location

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00935, Puerto Rico

Location

Related Publications (4)

• Shire NJ, Welge JA, Sherman KE. Response rates to pegylated interferon and ribavirin in HCV/HIV coinfection: a research synthesis. J Viral Hepat. 2007 Apr;14(4):239-48. doi: 10.1111/j.1365-2893.2006.00824.x.

  PMID: 17381715 BACKGROUND

• Kwo PY, Lawitz EJ, McCone J, Schiff ER, Vierling JM, Pound D, Davis MN, Galati JS, Gordon SC, Ravendhran N, Rossaro L, Anderson FH, Jacobson IM, Rubin R, Koury K, Pedicone LD, Brass CA, Chaudhri E, Albrecht JK; SPRINT-1 investigators. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet. 2010 Aug 28;376(9742):705-16. doi: 10.1016/S0140-6736(10)60934-8. Epub 2010 Aug 6.

  PMID: 20692693 BACKGROUND

• The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).

  BACKGROUND

• Sherman KE, Kang M, Sterling R, Umbleja T, Marks K, Alston-Smith B, Greaves W, Butt A. BIRTH: A Phase 3 Trial of Boceprevir/Pegylated Interferon/Ribavirin in HCV/HIV. IDWeek. San Diego, CA. October, 2015. [Abstract 903]

  RESULT

MeSH Terms

Conditions

HIV Infections; Hepatitis C

Interventions

Ribavirin; N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hepatitis, Viral, Human; Flaviviridae Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: ACTG ClinicalTrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Adeel A Butt, MD, MS

  University of Pittsburgh

  STUDY CHAIR

• Kenneth E Sherman, MD, PhD

  University of Cincinnati CRS

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2011
• First Posted: December 1, 2011
• Study Start: April 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: November 4, 2021
• Results First Posted: May 10, 2016

Record last verified: 2016-06

Locations

PR (1); US (42)