Vicriviroc (SCH 417690) Treatment Protocol in Human Immunodeficiency Virus (HIV)-Infected Participants: A Rollover Study for ACTG Protocol A5211 (P04100)
Primary Purpose
HIV, HIV Infections
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Vicriviroc maleate
Sponsored by
About this trial
This is an interventional treatment trial for HIV focused on measuring Treatment Experienced
Eligibility Criteria
Inclusion Criteria:
- Successful completion of ACTG Protocol A5211, or favorable response in A5211 but discontinued due to tropism shift, or screened for A5211 and met inclusion/exclusion criteria but unable to enroll due to protocol closure.
- Participants must also be on a ritonavir-containing antiretroviral regimen at entry, and have acceptable hematologic and laboratory parameters.
- Female participants of reproductive potential must agree to use 2 reliable methods of contraception, including a barrier method, and must have a negative urine pregnancy test prior to dosing.
Exclusion Criteria:
- History of seizure or drug use that increases risk of seizure, current use of CYP3A4 inducers, prior history of malignancy, active drug or alcohol use or dependence that would interfere with study requirements
- Female participants who are breast-feeding, pregnant, or plan to become pregnant
- Participation in a clinical trial with another investigational drug.
- Participants with serious illness requiring systemic therapy and/or hospitalization must not begin VCV (if not already on VCV) until participant completes therapy or is clinically stable on therapy for at least 14 days prior to enrollment.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
VCV 30 mg
Arm Description
Participants take VCV 30 mg once daily.
Outcomes
Primary Outcome Measures
Percentage of Participants With ≥1 Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment.
Percentage of Participants Discontinuing Study Therapy Due to AEs
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment.
Percentage of Participants With ≥1 Serious Adverse Events (SAEs)
An SAE is any adverse occurrence that results in death; is life-threatening; results in a persistent disability; requires in-patient hospitalization or prolongs hospitalization; or is a congenital anomaly/birth defect.
Percentage of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL
The percentage of participants with HIV RNA <50 copies/mL at each time point is reported. For this measure, "month" was defined as each 28-day period on study treatment. The Roche Amplicor® HIV-1 monitor test was used to quantify HIV RNA.
Percentage of Participants With HIV RNA >50 to <400 Copies/mL
The percentage of participants with HIV RNA >50 to <400 copies/mL at each time point is reported. For this measure, "month" was defined as each 28-day period on study treatment. The Roche Amplicor® HIV-1 monitor test was used to quantify HIV RNA.
Percentage of Participants With HIV RNA ≥400 Copies/mL
The percentage of participants with HIV RNA ≥400 copies/mL at each time point is reported. For this measure, "month" was defined as each 28-day period on study treatment. The Roche Amplicor® HIV-1 monitor test was used to quantify HIV RNA.
Number of Participants With Coreceptor Tropism Shifts From Baseline
The number of participants with non reportable (NR) tropism, CCR5 (R5) tropism, or dual/mixed CCR5/CXCR4 (DM/X4) tropism at baseline, who had NR, R5, or DM/X4 tropism at the time of virologic failure (VF) is reported. The definition of VF is an increase in HIV RNA level >0.5 log10 copies/mL compared to the baseline HIV RNA level.
Mean Change From Baseline in CD4/CD8 Cell Counts
The mean change from baseline in CD4/CD8 counts throughout P4100 until the time of VF is reported. "Month" was defined as each 28-day period on study treatment. A fluorescent-activated cell sorter (FACS) analysis was used to quantify CD4/CD8 lymphocytes. The definition of VF is an increase in HIV RNA level >0.5 log10 copies/mL compared to the baseline HIV RNA level.
Number of Participants With Reduced Susceptibility to VCV
The total number of participants with viruses having phenotypic resistance to VCV is reported. Viruses exhibiting both maximum percent inhibition (MPI) plateau values of <85% and relative MPI (R-MPI) values of <0.9 (based on the PhenoSense HIV entry assay) were considered to have phenotypic resistance to VCV.
Number of Participants With AIDS-defining Events (ADEs)
The number of participants with ADEs is reported. An ADE is an SAE that is expected in the course of disease and not considered related to study intervention. The sponsor identified events that met ADE criteria based on the 1993 Centers for Disease Control (CDC) Revised Classification System.
Number of Participants With New Infections
The number of participants with new infections is reported.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00686829
Brief Title
Vicriviroc (SCH 417690) Treatment Protocol in Human Immunodeficiency Virus (HIV)-Infected Participants: A Rollover Study for ACTG Protocol A5211 (P04100)
Official Title
Vicriviroc (SCH 417690) Treatment Protocol in HIV-Infected Subjects: A Rollover Study for ACTG Protocol A5211
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
June 30, 2005 (Actual)
Primary Completion Date
October 21, 2010 (Actual)
Study Completion Date
October 21, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to provide open-label vicriviroc (VCV) to human immunodeficiency virus (HIV) treatment-experienced participants who successfully completed 48 weeks of treatment on Acquired Immunodeficiency Syndrome (AIDS) Clinical Trial Group (ACTG) protocol A5211 (or who responded favorably to treatment but discontinued participation due to viral tropism shifts), and participants who screened for ACTG A5211 and met all inclusion/exclusion criteria, but were unable to enroll due to protocol closure.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV, HIV Infections
Keywords
Treatment Experienced
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
79 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VCV 30 mg
Arm Type
Experimental
Arm Description
Participants take VCV 30 mg once daily.
Intervention Type
Drug
Intervention Name(s)
Vicriviroc maleate
Other Intervention Name(s)
SCH 417690
Intervention Description
VCV 30 mg tablet once daily by mouth.
Primary Outcome Measure Information:
Title
Percentage of Participants With ≥1 Adverse Events (AEs)
Description
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment.
Time Frame
Up to discontinuation of commercial VCV availability (up to approximately 5.5 years)
Title
Percentage of Participants Discontinuing Study Therapy Due to AEs
Description
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment.
Time Frame
Up to discontinuation of commercial VCV availability (up to approximately 5.5 years)
Title
Percentage of Participants With ≥1 Serious Adverse Events (SAEs)
Description
An SAE is any adverse occurrence that results in death; is life-threatening; results in a persistent disability; requires in-patient hospitalization or prolongs hospitalization; or is a congenital anomaly/birth defect.
Time Frame
Up to discontinuation of commercial VCV availability (up to approximately 5.5 years)
Title
Percentage of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL
Description
The percentage of participants with HIV RNA <50 copies/mL at each time point is reported. For this measure, "month" was defined as each 28-day period on study treatment. The Roche Amplicor® HIV-1 monitor test was used to quantify HIV RNA.
Time Frame
Every 12 months up to 60 months
Title
Percentage of Participants With HIV RNA >50 to <400 Copies/mL
Description
The percentage of participants with HIV RNA >50 to <400 copies/mL at each time point is reported. For this measure, "month" was defined as each 28-day period on study treatment. The Roche Amplicor® HIV-1 monitor test was used to quantify HIV RNA.
Time Frame
Every 12 months up to 60 months
Title
Percentage of Participants With HIV RNA ≥400 Copies/mL
Description
The percentage of participants with HIV RNA ≥400 copies/mL at each time point is reported. For this measure, "month" was defined as each 28-day period on study treatment. The Roche Amplicor® HIV-1 monitor test was used to quantify HIV RNA.
Time Frame
Every 12 months up to 60 months
Title
Number of Participants With Coreceptor Tropism Shifts From Baseline
Description
The number of participants with non reportable (NR) tropism, CCR5 (R5) tropism, or dual/mixed CCR5/CXCR4 (DM/X4) tropism at baseline, who had NR, R5, or DM/X4 tropism at the time of virologic failure (VF) is reported. The definition of VF is an increase in HIV RNA level >0.5 log10 copies/mL compared to the baseline HIV RNA level.
Time Frame
Baseline (Week 48 of ACTG study A5211) and time of VF in P4100, assessed up to approximately 5.5 years
Title
Mean Change From Baseline in CD4/CD8 Cell Counts
Description
The mean change from baseline in CD4/CD8 counts throughout P4100 until the time of VF is reported. "Month" was defined as each 28-day period on study treatment. A fluorescent-activated cell sorter (FACS) analysis was used to quantify CD4/CD8 lymphocytes. The definition of VF is an increase in HIV RNA level >0.5 log10 copies/mL compared to the baseline HIV RNA level.
Time Frame
Baseline (Week 48 of ACTG study A5211) and up to time of VF in P4100, assessed up to approximately 5.5 years
Title
Number of Participants With Reduced Susceptibility to VCV
Description
The total number of participants with viruses having phenotypic resistance to VCV is reported. Viruses exhibiting both maximum percent inhibition (MPI) plateau values of <85% and relative MPI (R-MPI) values of <0.9 (based on the PhenoSense HIV entry assay) were considered to have phenotypic resistance to VCV.
Time Frame
Up to time of VF in P4100, assessed up to approximately 5.5 years
Title
Number of Participants With AIDS-defining Events (ADEs)
Description
The number of participants with ADEs is reported. An ADE is an SAE that is expected in the course of disease and not considered related to study intervention. The sponsor identified events that met ADE criteria based on the 1993 Centers for Disease Control (CDC) Revised Classification System.
Time Frame
Up to discontinuation of commercial VCV availability (up to approximately 5.5 years)
Title
Number of Participants With New Infections
Description
The number of participants with new infections is reported.
Time Frame
Up to discontinuation of commercial VCV availability (up to approximately 5.5 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Successful completion of ACTG Protocol A5211, or favorable response in A5211 but discontinued due to tropism shift, or screened for A5211 and met inclusion/exclusion criteria but unable to enroll due to protocol closure.
Participants must also be on a ritonavir-containing antiretroviral regimen at entry, and have acceptable hematologic and laboratory parameters.
Female participants of reproductive potential must agree to use 2 reliable methods of contraception, including a barrier method, and must have a negative urine pregnancy test prior to dosing.
Exclusion Criteria:
History of seizure or drug use that increases risk of seizure, current use of CYP3A4 inducers, prior history of malignancy, active drug or alcohol use or dependence that would interfere with study requirements
Female participants who are breast-feeding, pregnant, or plan to become pregnant
Participation in a clinical trial with another investigational drug.
Participants with serious illness requiring systemic therapy and/or hospitalization must not begin VCV (if not already on VCV) until participant completes therapy or is clinically stable on therapy for at least 14 days prior to enrollment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
20672447
Citation
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.
Results Reference
result
PubMed Identifier
20400411
Citation
Yeh TM, Evans SR, Gulick RM, Clifford DB. Vicriviroc and peripheral neuropathy: results from AIDS Clinical Trials Group 5211. HIV Clin Trials. 2010 Jan-Feb;11(1):51-8. doi: 10.1310/hct1101-51.
Results Reference
result
PubMed Identifier
19191652
Citation
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.
Results Reference
result
Learn more about this trial
Vicriviroc (SCH 417690) Treatment Protocol in Human Immunodeficiency Virus (HIV)-Infected Participants: A Rollover Study for ACTG Protocol A5211 (P04100)
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