Safety and Effectiveness of the Oral HIV Entry Inhibitor Vicriviroc in HIV Infected Patients

NCT00082498 | Completed Phase 2

• 4 other identifiers: A521110097ACTG A52115K24AI051966-03
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 30

Brief Summary

New treatment options are critical for treatment-experienced HIV infected patients with drug resistance. HIV entry inhibitors have been shown effective in patients with resistance to other anti-HIV drugs. This study will test the safety and effectiveness of three different doses of vicriviroc (formerly known as Schering D, SCH-D, or SCH 417690) in HIV infected patients.

Conditions

HIV Infections

Keywords

SCH-D; Schering D; Treatment Experienced; Entry Inhibitors; Fusion Inhibitors; Vicriviroc

Outcome Measures

Primary Outcomes (1)

• Change in HIV-1 viral load

  From baseline to Day 14

Secondary Outcomes (6)

• Safety and tolerability

  Throughout the study

• Virologic and immunologic outcomes

  Throughout the study

• Clinical outcomes

  Throughout the study

• Pharmacokinetic outcomes

  At Weeks 2 and 8

• Viral coreceptor phenotype

  At study entry, Day 4, and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48

Study Arms (4)

1

PLACEBO COMPARATOR

Group 1 will receive placebo

Drug: Placebo

2

EXPERIMENTAL

Group 2 will receive 5 mg vicriviroc daily

Drug: SCH-D (vicriviroc)

3

EXPERIMENTAL

Group 3 will receive 10 mg vicriviroc daily

Drug: SCH-D (vicriviroc)

4

EXPERIMENTAL

Group 4 will receive 15 mg vicriviroc daily

Drug: SCH-D (vicriviroc)

Interventions

SCH-D (vicriviroc) DRUG

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.

2; 3; 4

Placebo DRUG

Patients in Group 1 will receive placebo.

1

Eligibility Criteria

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

You may qualify if:

• HIV infected
• 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.

You may not qualify if:

• Hepatitis C antibody and RNA positive
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator

Study Sites (30)

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

Santa Clara Valley Med. Ctr.

San Jose, California, 95128, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, 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

Rush University CRS

Chicago, Illinois, 60612, United States

Location

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, 46202, 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

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110, United States

Location

Beth Israel Med. Ctr., ACTU

New York, New York, 10003, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10011, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Weill Cornell Uptown CRS

New York, New York, 10065, United States

Location

Trillium Health ACTG CRS

Rochester, New York, 14607, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27514, United States

Location

Case CRS

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, 15213-2582, 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

Univ. of Texas Medical Branch, ACTU

Galveston, Texas, 77555-0435, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104, United States

Location

Related Publications (9)

• 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.

  PMID: 16091227 BACKGROUND

• Meanwell NA, Kadow JF. Inhibitors of the entry of HIV into host cells. Curr Opin Drug Discov Devel. 2003 Jul;6(4):451-61.

  PMID: 12951808 BACKGROUND

• Reeves JD, Piefer AJ. Emerging drug targets for antiretroviral therapy. Drugs. 2005;65(13):1747-66. doi: 10.2165/00003495-200565130-00002.

  PMID: 16114975 BACKGROUND

• 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).

  BACKGROUND

• 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.

  PMID: 15090884 BACKGROUND

• 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.

  PMID: 16304152 BACKGROUND

• 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.

  PMID: 17243065 RESULT

• 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.

  PMID: 20672447 DERIVED

• 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.

  PMID: 19191652 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

vicriviroc

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

Study Officials

• Roy M. Gulick, MD, MPH

  Cornell HIV Clinical Trials Unit

  STUDY CHAIR

• Charles Flexner, MD

  Johns Hopkins University Hospital

  STUDY CHAIR

• Daniel Kuritzkes, MD

  Harvard Medical School, Partners AIDS Research Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2004
• First Posted: May 12, 2004
• Study Start: May 1, 2004
• Primary Completion: December 1, 2005
• Study Completion: January 1, 2011
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

US (30)