Safety and Effectiveness of the Oral HIV Entry Inhibitor Vicriviroc in HIV Infected Patients
NCT ID: NCT00082498
Last Updated: 2021-11-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
119 participants
INTERVENTIONAL
2004-05-31
2011-01-31
Brief Summary
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Detailed Description
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The study will last at least 48 weeks, but no more than 5 years. There are 3 steps in this study. Patients will be randomly assigned to one of 4 groups. Group 1 will receive placebo; Group 2 will receive 5 mg vicriviroc daily; Group 3 will receive 10 mg vicriviroc daily; and Group 4 will receive 15 mg vicriviroc daily. If at or after Week 16 a participant's viral load has not met certain criteria, a dose increase of vicriviroc may occur and the participant will enter Step 2. As of 10/12/05, patients in Group 2 and any patients who entered Step 2 following virologic failure in Step 1 will be unblinded and offered either 15 mg vicriviroc daily through this study or the option of seeking alternative treatment. All patients will continue their current ART (not provided by the study). After two weeks, patients will receive ART optimized by the results of genotypic/phenotypic testing performed at study screening. All participants who have received or are receiving vicriviroc will enter Step 3 and be followed for an additional 4 years. Participants who complete the study may be eligible to receive vicriviroc through a rollover study sponsored by Schering-Plough, the drug's manufacturer.
Physical exams and blood collection will occur at study entry, Day 4, and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48. Additionally, blood will be drawn twice, at least 2 hours apart, at both Weeks 2 and 8 for vicriviroc pharmacokinetic analysis. Patients will undergo an electrocardiogram (EKG) at Weeks 2, 8, 24, and 48. Patients will be assessed for peripheral neuropathy at study entry and Weeks 24 and 48, and will be asked to complete an adherence questionnaire at entry and Weeks 2, 8, 16, 24, 32, 40, and 48. For Step 3 participants undergoing follow-up, physical exams and blood work will occur every 6 months for 4 years.
Five participants currently enrolled at four sites that are no longer receiving funding and who will not be transferred or redirected to a site within their proximity will be subject to the following changes. There will no longer be follow-up visits per the schedule of events described in the protocol. Instead, participants will have their follow-up limited to self-report through telephone interviews to ascertain vital status, occurrence of malignancies (if any), and collection of information such as HIV-1 RNA and CD4 cell count. For these participants only, the HIV-1 RNA and CD4 cell count will be done as part of the participant's clinical care and will not be paid for by the study. The follow-up telephone interviews will be conducted at six-month intervals using the script provided by the study team.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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1
Group 1 will receive placebo
Placebo
Patients in Group 1 will receive placebo.
2
Group 2 will receive 5 mg vicriviroc daily
SCH-D (vicriviroc)
Group 2 will receive 5 mg vicriviroc daily; Group 3 will receive 10 mg vicriviroc daily; and Group 4 will receive 15 mg vicriviroc daily. If at or after Week 16 a participant's viral load has not met certain criteria, a dose increase of vicriviroc may occur and the participant will enter Step 2. As of 10/12/05, patients in Group 2 and any patients who entered Step 2 following virologic failure in Step 1 will be unblinded and offered either 15 mg vicriviroc daily through this study or the option of seeking alternative treatment.
3
Group 3 will receive 10 mg vicriviroc daily
SCH-D (vicriviroc)
Group 2 will receive 5 mg vicriviroc daily; Group 3 will receive 10 mg vicriviroc daily; and Group 4 will receive 15 mg vicriviroc daily. If at or after Week 16 a participant's viral load has not met certain criteria, a dose increase of vicriviroc may occur and the participant will enter Step 2. As of 10/12/05, patients in Group 2 and any patients who entered Step 2 following virologic failure in Step 1 will be unblinded and offered either 15 mg vicriviroc daily through this study or the option of seeking alternative treatment.
4
Group 4 will receive 15 mg vicriviroc daily
SCH-D (vicriviroc)
Group 2 will receive 5 mg vicriviroc daily; Group 3 will receive 10 mg vicriviroc daily; and Group 4 will receive 15 mg vicriviroc daily. If at or after Week 16 a participant's viral load has not met certain criteria, a dose increase of vicriviroc may occur and the participant will enter Step 2. As of 10/12/05, patients in Group 2 and any patients who entered Step 2 following virologic failure in Step 1 will be unblinded and offered either 15 mg vicriviroc daily through this study or the option of seeking alternative treatment.
Interventions
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SCH-D (vicriviroc)
Group 2 will receive 5 mg vicriviroc daily; Group 3 will receive 10 mg vicriviroc daily; and Group 4 will receive 15 mg vicriviroc daily. If at or after Week 16 a participant's viral load has not met certain criteria, a dose increase of vicriviroc may occur and the participant will enter Step 2. As of 10/12/05, patients in Group 2 and any patients who entered Step 2 following virologic failure in Step 1 will be unblinded and offered either 15 mg vicriviroc daily through this study or the option of seeking alternative treatment.
Placebo
Patients in Group 1 will receive placebo.
Eligibility Criteria
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Inclusion Criteria
* Experiencing virologic failure on current ART regimen
* Current ART regimen contains ritonavir (100 to 800 mg/day) and has been stable for at least 8 weeks prior to study entry. If amprenavir or fosamprenavir is part of the regimen, 200 to 800 mg/day ritonavir must be used for at least 2 weeks prior to study entry.
* Experienced virologic failure on at least one ART regimen containing 3 or more drugs prior to current failing regimen
* CD4 count of 50 cells/mm3 or more within 6 weeks prior to study entry
* HIV viral load of 5,000 copies/ml or more within 6 weeks prior to study entry
* HIV strain of R5-only phenotype within 6 weeks prior to study entry
* Willing to use acceptable forms of contraception
* Able and willing to adhere to study dose and visit schedules
* HIV viral load not suppressed by at least 1log10 below baseline viral load by Week 16 or after
* QTc interval on EKG less than 500 msec, and less than 60 msec increase from baseline within 14 days of Step 2 entry
* Use of vicriviroc in Step 1 or 2 of this study or the Schering rollover study. Participants who are currently not taking vicriviroc are eligible.
Exclusion Criteria
* Hepatitis B surface antigen positive
* Efavirenz or nevirapine use within 8 weeks of study entry
* Vaccination within 2 weeks prior to study screening
* Investigational agents within 30 days prior to study entry
* Systemic cancer chemotherapy or other systemic cytotoxic agents within 30 days prior to study entry
* Immunosuppressants within 30 days prior to study entry. Systemic corticosteroids at replacement doses (10 mg/day prednisone or less) are not excluded.
* Immunomodulators within 30 days prior to study entry
* Considered at risk for seizure: history of seizure, recent history of head trauma with loss of consciousness, central nervous system (CNS) tumors, or other CNS problems that, in the opinion of the investigator, pose increased risk for seizure
* Medications to prevent seizures or with the potential to cause seizures within 30 days prior to study entry
* Allergy to SCH 417690 or its components
* Alcohol or drug abuse that, in the opinion of the investigator, would interfere with the study
* Serious illness requiring systemic treatment or hospitalization. A patient who is clinically stable on therapy is not excluded.
* Any clinically significant disease or condition that, in the opinion of the investigator, may interfere with the study
* Require certain medications
* Pregnancy or breastfeeding
* Have X4 or X4/R5 tropic virus, as determined by the HIV-1 coreceptor tropism assay
* Intend to use efavirenz or nevirapine in background ART regimen
* Allergy to vicriviroc or its formulations
* Pregnancy
18 Years
ALL
No
Sponsors
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Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
NETWORK
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Roy M. Gulick, MD, MPH
Role: STUDY_CHAIR
Cornell HIV Clinical Trials Unit
Charles Flexner, MD
Role: STUDY_CHAIR
Johns Hopkins University Hospital
Daniel Kuritzkes, MD
Role: STUDY_CHAIR
Harvard Medical School, Partners AIDS Research Center
Locations
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UCLA CARE Center CRS
Los Angeles, California, United States
Stanford AIDS Clinical Trials Unit CRS
Palo Alto, California, United States
UCSD Antiviral Research Center CRS
San Diego, California, United States
Ucsf Hiv/Aids Crs
San Francisco, California, United States
Santa Clara Valley Med. Ctr.
San Jose, California, United States
University of Colorado Hospital CRS
Aurora, Colorado, United States
Georgetown University CRS (GU CRS)
Washington D.C., District of Columbia, United States
The Ponce de Leon Center CRS
Atlanta, Georgia, United States
Rush University CRS
Chicago, Illinois, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 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
Washington University Therapeutics (WT) CRS
St Louis, Missouri, United States
Beth Israel Med. Ctr., ACTU
New York, New York, United States
Weill Cornell Chelsea CRS
New York, New York, United States
NY Univ. HIV/AIDS CRS
New York, New York, United States
Weill Cornell Uptown CRS
New York, New York, United States
Trillium Health ACTG CRS
Rochester, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
Chapel Hill CRS
Chapel Hill, North Carolina, United States
Case CRS
Cleveland, Ohio, United States
MetroHealth CRS
Cleveland, Ohio, 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
The Miriam Hospital Clinical Research Site (TMH CRS) CRS
Providence, Rhode Island, United States
Vanderbilt Therapeutics (VT) CRS
Nashville, Tennessee, United States
Univ. of Texas Medical Branch, ACTU
Galveston, Texas, United States
University of Washington AIDS CRS
Seattle, Washington, United States
Countries
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References
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Marks K, Gulick RM. New antiretroviral agents for the treatment of HIV infection. Curr HIV/AIDS Rep. 2004 Jun;1(2):82-8. doi: 10.1007/s11904-004-0012-0.
Meanwell NA, Kadow JF. Inhibitors of the entry of HIV into host cells. Curr Opin Drug Discov Devel. 2003 Jul;6(4):451-61.
Reeves JD, Piefer AJ. Emerging drug targets for antiretroviral therapy. Drugs. 2005;65(13):1747-66. doi: 10.2165/00003495-200565130-00002.
Schurmann D et al. SCH D: Antiviral activity of a CCR5 receptor antagonist. 11th Conf Retro and Opportun Infect. 2004 Feb 8-11 (abstract no 140LB).
Shaheen F, Collman RG. Co-receptor antagonists as HIV-1 entry inhibitors. Curr Opin Infect Dis. 2004 Feb;17(1):7-16. doi: 10.1097/00001432-200402000-00003.
Strizki JM, Tremblay C, Xu S, Wojcik L, Wagner N, Gonsiorek W, Hipkin RW, Chou CC, Pugliese-Sivo C, Xiao Y, Tagat JR, Cox K, Priestley T, Sorota S, Huang W, Hirsch M, Reyes GR, Baroudy BM. Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2005 Dec;49(12):4911-9. doi: 10.1128/AAC.49.12.4911-4919.2005.
Wilkin TJ, Su Z, Kuritzkes DR, Hughes M, Flexner C, Gross R, Coakley E, Greaves W, Godfrey C, Skolnik PR, Timpone J, Rodriguez B, Gulick RM. HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211. Clin Infect Dis. 2007 Feb 15;44(4):591-5. doi: 10.1086/511035. Epub 2007 Jan 17.
Wilkin TJ, Su Z, Krambrink A, Long J, Greaves W, Gross R, Hughes MD, Flexner C, Skolnik PR, Coakley E, Godfrey C, Hirsch M, Kuritzkes DR, Gulick RM. Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in HIV-1-infected treatment-experienced patients. J Acquir Immune Defic Syndr. 2010 Aug;54(5):470-6. doi: 10.1097/qai.0b013e3181e2cba0.
Tsibris AM, Paredes R, Chadburn A, Su Z, Henrich TJ, Krambrink A, Hughes MD, Aberg JA, Currier JS, Tashima K, Godfrey C, Greaves W, Flexner C, Skolnik PR, Wilkin TJ, Gulick RM, Kuritzkes DR. Lymphoma diagnosis and plasma Epstein-Barr virus load during vicriviroc therapy: results of the AIDS Clinical Trials Group A5211. Clin Infect Dis. 2009 Mar 1;48(5):642-9. doi: 10.1086/597007.
Other Identifiers
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10097
Identifier Type: REGISTRY
Identifier Source: secondary_id
ACTG A5211
Identifier Type: -
Identifier Source: secondary_id
A5211
Identifier Type: -
Identifier Source: org_study_id