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

HIV Infections Clinical Trial

Official title:

Phase II, Randomized, Double-Blind Study of the Safety and Efficacy of Vicriviroc (An Orally Administered HIV-1 Entry Inhibitor) in HIV-Infected, Treatment-Experienced Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00082498
• Other study ID #: A5211
• Secondary ID: 10097ACTG A52115
• Status: Completed
• Phase: Phase 2
• Start date: May 2004
• Est. completion date: January 2011

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Vicriviroc is an oral HIV-1 entry inhibitor that targets the CCR5 receptor of T cells. Vicriviroc has been shown safe, well-tolerated, and active in Phase I clinical trials in treatment-naive HIV infected patients. The goal of this study is to evaluate the antiretroviral activity of three dose levels of vicriviroc in HIV infected, treatment-experienced patients who are failing their current ritonavir-containing antiretroviral therapy (ART).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: January 2011
• Est. primary completion date: December 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Note: This study was closed to screening on 09/20/05 and to enrollment on 10/20/05.

Inclusion Criteria for Step 1:

• 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

Inclusion Criteria for Step 2:

• 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

Inclusion Criteria for Step 3:

• 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 for Step 1:

• 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

• Pregnancy or breastfeeding

Exclusion Criteria for Step 2:

• 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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	The Ponce de Leon Center CRS	Atlanta	Georgia
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	Bmc Actg Crs	Boston	Massachusetts
United States	Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS	Boston	Massachusetts
United States	Massachusetts General Hospital CRS (MGH CRS)	Boston	Massachusetts
United States	Chapel Hill CRS	Chapel Hill	North Carolina
United States	Rush University CRS	Chicago	Illinois
United States	Case CRS	Cleveland	Ohio
United States	MetroHealth CRS	Cleveland	Ohio
United States	Ohio State University CRS	Columbus	Ohio
United States	Univ. of Texas Medical Branch, ACTU	Galveston	Texas
United States	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana
United States	UCLA CARE Center CRS	Los Angeles	California
United States	Vanderbilt Therapeutics (VT) CRS	Nashville	Tennessee
United States	Beth Israel Med. Ctr., ACTU	New York	New York
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Weill Cornell Chelsea CRS	New York	New York
United States	Weill Cornell Uptown CRS	New York	New York
United States	Stanford AIDS Clinical Trials Unit CRS	Palo Alto	California
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	Trillium Health ACTG CRS	Rochester	New York
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	Washington University Therapeutics (WT) CRS	Saint Louis	Missouri
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 Washington AIDS CRS	Seattle	Washington
United States	Georgetown University CRS (GU CRS)	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	AIDS Clinical Trials Group

Country where clinical trial is conducted

United States, 

References & Publications (7)

Marks K, Gulick RM. New antiretroviral agents for the treatment of HIV infection. Curr HIV/AIDS Rep. 2004 Jun;1(2):82-8. Review. — View Citation

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

Reeves JD, Piefer AJ. Emerging drug targets for antiretroviral therapy. Drugs. 2005;65(13):1747-66. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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 C — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HIV-1 viral load		From baseline to Day 14
Secondary	Safety and tolerability		Throughout the study
Secondary	Virologic and immunologic outcomes		Throughout the study
Secondary	Clinical outcomes		Throughout the study
Secondary	Pharmacokinetic outcomes		At Weeks 2 and 8
Secondary	Viral coreceptor phenotype		At study entry, Day 4, and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Secondary	Adherence measures		At study entry and Weeks 2, 8, 16, 24, 32, 40, and 48

External Links

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