HIV, HIV Infections
Conditions
Keywords
Treatment Experienced
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.
Interventions
VCV 30 mg tablet once daily by mouth.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥1 Adverse Events (AEs) | Up to discontinuation of commercial VCV availability (up to approximately 5.5 years) | 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 | Up to discontinuation of commercial VCV availability (up to approximately 5.5 years) | 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) | Up to discontinuation of commercial VCV availability (up to approximately 5.5 years) | 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 | Every 12 months up to 60 months | 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 | Every 12 months up to 60 months | 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 | Every 12 months up to 60 months | 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 | Baseline (Week 48 of ACTG study A5211) and time of VF in P4100, assessed up to approximately 5.5 years | 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 | Baseline (Week 48 of ACTG study A5211) and up to time of VF in P4100, assessed up to approximately 5.5 years | 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 | Up to time of VF in P4100, assessed up to approximately 5.5 years | 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) | Up to discontinuation of commercial VCV availability (up to approximately 5.5 years) | 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 | Up to discontinuation of commercial VCV availability (up to approximately 5.5 years) | The number of participants with new infections is reported. |
Participant flow
Recruitment details
Participants with human immunodeficiency virus (HIV) infection enrolled in AIDS Clinical Trial Group (ACTG) study A5211 (NCT00082498) and (1) completed the 48-week phase, or (2) had detectable alpha-chemokine receptor 4 (CXCR4)-tropic virus but maintained a virologic response and no drop in cluster of differentiation 4 (CD4)/CD8 count from baseline, or (3) met all inclusion/exclusion criteria but were unable to enroll in ACTG A5211 due to protocol closure prior to their randomization and dosing.
Participants by arm
| Arm | Count |
|---|---|
| VCV 30 mg Participants took VCV 30 mg once daily. | 79 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Lack of Efficacy | 6 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Sponsor discontinued VCV | 47 |
| Overall Study | Withdrawal by Subject | 14 |
Baseline characteristics
| Characteristic | VCV 30 mg |
|---|---|
| Age, Continuous | 49 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 60 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 79 |
| other Total, other adverse events | 70 / 79 |
| serious Total, serious adverse events | 38 / 79 |
Outcome results
Primary
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.
Time frame: Baseline (Week 48 of ACTG study A5211) and up to time of VF in P4100, assessed up to approximately 5.5 years
Population: All treated participants with baseline and on-treatment CD4/CD8 data available are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 2 | -16.26 cells/mm^3 | Standard Deviation 103.83 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 4 | -17.70 cells/mm^3 | Standard Deviation 84.87 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 6 | 9.30 cells/mm^3 | Standard Deviation 95.38 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 8 | -0.20 cells/mm^3 | Standard Deviation 115.96 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 10 | 12.59 cells/mm^3 | Standard Deviation 97.84 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 12 | -13.81 cells/mm^3 | Standard Deviation 124.09 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 14 | 18.56 cells/mm^3 | Standard Deviation 106.18 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 16 | 21.63 cells/mm^3 | Standard Deviation 130.33 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 18 | 2.82 cells/mm^3 | Standard Deviation 108.52 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 20 | 19.71 cells/mm^3 | Standard Deviation 125.34 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 22 | 24.19 cells/mm^3 | Standard Deviation 94.37 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 24 | 32.04 cells/mm^3 | Standard Deviation 121.45 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 26 | 34.36 cells/mm^3 | Standard Deviation 128.99 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 28 | 36.10 cells/mm^3 | Standard Deviation 120.75 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 30 | 38.10 cells/mm^3 | Standard Deviation 113.8 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 32 | 47.59 cells/mm^3 | Standard Deviation 137.15 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 34 | 61.93 cells/mm^3 | Standard Deviation 109.71 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 36 | 43.63 cells/mm^3 | Standard Deviation 136.85 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 38 | 90.81 cells/mm^3 | Standard Deviation 140.11 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 40 | 75.53 cells/mm^3 | Standard Deviation 142.9 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 42 | 104.65 cells/mm^3 | Standard Deviation 187.14 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 44 | 91.61 cells/mm^3 | Standard Deviation 181.71 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 46 | 91.19 cells/mm^3 | Standard Deviation 165.33 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 48 | 93.93 cells/mm^3 | Standard Deviation 174.36 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 50 | 128.12 cells/mm^3 | Standard Deviation 189.94 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 52 | 107.41 cells/mm^3 | Standard Deviation 170.97 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 54 | 136.00 cells/mm^3 | Standard Deviation 211.98 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 56 | 129.87 cells/mm^3 | Standard Deviation 196.8 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 58 | 188.81 cells/mm^3 | Standard Deviation 152.93 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 60 | 122.60 cells/mm^3 | Standard Deviation 191.32 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 62 | 132.54 cells/mm^3 | Standard Deviation 118.87 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 64 | 147.50 cells/mm^3 | Standard Deviation 197.12 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 66 | 283.50 cells/mm^3 | Standard Deviation 2.12 |
| VCV 30 mg | Mean Change From Baseline in CD4/CD8 Cell Counts | Month 68 | 300.00 cells/mm^3 | Standard Deviation 50.91 |
Primary
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.
Time frame: Up to discontinuation of commercial VCV availability (up to approximately 5.5 years)
Population: All treated participants are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VCV 30 mg | Number of Participants With AIDS-defining Events (ADEs) | Plasmablastic Lymphoma | 1 Participants |
| VCV 30 mg | Number of Participants With AIDS-defining Events (ADEs) | Kaposi's Sarcoma | 1 Participants |
Primary
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.
Time frame: Baseline (Week 48 of ACTG study A5211) and time of VF in P4100, assessed up to approximately 5.5 years
Population: All treated participants with baseline and VF tropism data available are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VCV 30 mg | Number of Participants With Coreceptor Tropism Shifts From Baseline | NR Baseline to NR VF | 45 Participants |
| VCV 30 mg | Number of Participants With Coreceptor Tropism Shifts From Baseline | NR at Baseline to R5 VF | 10 Participants |
| VCV 30 mg | Number of Participants With Coreceptor Tropism Shifts From Baseline | NR Baseline to DM/X4 VF | 5 Participants |
| VCV 30 mg | Number of Participants With Coreceptor Tropism Shifts From Baseline | R5 baseline to R5 VF | 11 Participants |
| VCV 30 mg | Number of Participants With Coreceptor Tropism Shifts From Baseline | R5 baseline to NR VF | 3 Participants |
| VCV 30 mg | Number of Participants With Coreceptor Tropism Shifts From Baseline | R5 baseline to DM/X4 VF | 1 Participants |
| VCV 30 mg | Number of Participants With Coreceptor Tropism Shifts From Baseline | DM/X4 baseline to DM/X4 VF | 3 Participants |
| VCV 30 mg | Number of Participants With Coreceptor Tropism Shifts From Baseline | DM/X4 baseline to R5 VF | 1 Participants |
Primary
Number of Participants With New Infections
The number of participants with new infections is reported.
Time frame: Up to discontinuation of commercial VCV availability (up to approximately 5.5 years)
Population: All treated participants are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VCV 30 mg | Number of Participants With New Infections | Herpes simplex virus infection | 6 Participants |
| VCV 30 mg | Number of Participants With New Infections | Upper respiratory tract infection | 39 Participants |
Primary
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.
Time frame: Up to time of VF in P4100, assessed up to approximately 5.5 years
Population: All treated participants are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VCV 30 mg | Number of Participants With Reduced Susceptibility to VCV | 7 Participants |
Primary
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.
Time frame: Up to discontinuation of commercial VCV availability (up to approximately 5.5 years)
Population: All treated participants are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VCV 30 mg | Percentage of Participants Discontinuing Study Therapy Due to AEs | 6 Percentage of Participants |
Primary
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.
Time frame: Up to discontinuation of commercial VCV availability (up to approximately 5.5 years)
Population: All treated participants are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VCV 30 mg | Percentage of Participants With ≥1 Adverse Events (AEs) | 91 Percentage of Participants |
Primary
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.
Time frame: Up to discontinuation of commercial VCV availability (up to approximately 5.5 years)
Population: All treated participants are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VCV 30 mg | Percentage of Participants With ≥1 Serious Adverse Events (SAEs) | 48 Percentage of Participants |
Primary
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.
Time frame: Every 12 months up to 60 months
Population: All treated participants with HIV RNA data available are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VCV 30 mg | Percentage of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL | Month 12 | 52 Percentage of Participants |
| VCV 30 mg | Percentage of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL | Month 24 | 64 Percentage of Participants |
| VCV 30 mg | Percentage of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL | Month 36 | 80 Percentage of Participants |
| VCV 30 mg | Percentage of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL | Month 48 | 89 Percentage of Participants |
| VCV 30 mg | Percentage of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL | Month 60 | 80 Percentage of Participants |
Primary
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.
Time frame: Every 12 months up to 60 months
Population: All treated participants with HIV RNA data available are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VCV 30 mg | Percentage of Participants With HIV RNA ≥400 Copies/mL | Month 12 | 35 Percentage of Participants |
| VCV 30 mg | Percentage of Participants With HIV RNA ≥400 Copies/mL | Month 24 | 25 Percentage of Participants |
| VCV 30 mg | Percentage of Participants With HIV RNA ≥400 Copies/mL | Month 36 | 8 Percentage of Participants |
| VCV 30 mg | Percentage of Participants With HIV RNA ≥400 Copies/mL | Month 48 | 9 Percentage of Participants |
| VCV 30 mg | Percentage of Participants With HIV RNA ≥400 Copies/mL | Month 60 | 5 Percentage of Participants |
Primary
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.
Time frame: Every 12 months up to 60 months
Population: All treated participants with HIV RNA data available are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VCV 30 mg | Percentage of Participants With HIV RNA >50 to <400 Copies/mL | Month 48 | 2 Percentage of Participants |
| VCV 30 mg | Percentage of Participants With HIV RNA >50 to <400 Copies/mL | Month 12 | 13 Percentage of Participants |
| VCV 30 mg | Percentage of Participants With HIV RNA >50 to <400 Copies/mL | Month 24 | 11 Percentage of Participants |
| VCV 30 mg | Percentage of Participants With HIV RNA >50 to <400 Copies/mL | Month 36 | 12 Percentage of Participants |
| VCV 30 mg | Percentage of Participants With HIV RNA >50 to <400 Copies/mL | Month 60 | 15 Percentage of Participants |