Health Volunteers, HIV Infections
Conditions
Keywords
ABX464, HIV infection
Brief summary
The purpose of the ABX464-005 study is to characterize the systemic and mucosal immunological sequelae associated with exposure to ABX464 and to explore selected immunological endpoints, compartmental pharmacokinetics, and pharmacodynamics.
Detailed description
The purpose of the ABX464-005 study is to characterize the systemic and mucosal immunological sequelae associated with exposure to ABX464 and to explore selected immunological endpoints, compartmental pharmacokinetics, and pharmacodynamics. The site will screen and enroll 12 HIV-infected subjects who will receive 150 mg ABX464 orally once daily for 28 days (Cohort 1). Following completion of this cohort a further 24 subjects will be enrolled: 12 HIV-uninfected subjects will receive 50 mg ABX464 orally once daily for 28 days (Cohort 2) and 12 HIV-infected subjects (Cohort 3) who will 50 mg ABX464 orally once daily for 84 days.
Interventions
DRUGABX464 150mg
ABX464 given orally at 150 mg per day from Day 0 to Day 28 (Cohort 1/ HIV infected subjects)
DRUGABX464 50mg
ABX464 given orally at 50 mg per day from Day 0 to Day 28 (Cohort 2 / non HIV infected subjects)
Sponsors
Abivax S.A.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Males aged 18-65 years; * Subjects with adequate hematological and biochemical laboratory parameters * Subjects should be able and willing to comply with study visits and procedures as per protocol; * Subjects should understand, sign and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures being performed; * Subjects must agree to use in addition to the condom, a second highly effective method (one for the subject and one for the partner) of contraception (defined as per the Clinical Trials Facilitation and Coordination Group (CTFG) Guidance). For HIV positive Subjects * Subjects with a positive HIV-1 serology at any time before the study entry. * Subjects treated for at least 12 months prior to screening with Dolutegravir or Raltegravir combined with either Tenofovir + Emtricitabine (TDF/FTC) or Abacavir + Lamivudine (ABC/3TC); * Subjects with HIV plasma viral load ≤ 50 copies/mL during the 6 months prior to screening with a maximum of 2 blips ≤ 1000 copies during this period; * Subjects' HIV-1 plasma viral load to be ≤ 100,000 copies/mL at any time beyond 6 months after the estimated date of primary infection;
Exclusion criteria
* History of allergic disease, anaphylaxis or reactions likely to be triggered or exacerbated by any component of investigational products; * Acute or chronic infectious disease other than HIV infection (include but not limited to viral hepatitis such as hepatitis B, hepatitis C, active tuberculosis, active syphilis \[i.e. currently treated\]. * Acute, chronic or history of clinically relevant pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable Central Nervous System (CNS) pathology, angina or cardiac arrhythmias, or any other clinically significant medical problems as determined by physical examination and/or laboratory screening tests and/or medical history; * Severe hepatic impairment; * Acute, chronic or history of immunodeficiency or autoimmune disease other than HIV infection;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 1, Day 28, Day 56, Day 84 and Day 112 | Pharmacokinetic parameters |
| Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 1, Day 28 and Day 84 | Pharmacokinetic parameters |
| Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 1, Day 28 and Day 84 | Pharmacokinetic parameters |
| Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 1, Day 28, Day 56, Day 84 and Day 112 | Pharmacokinetic parameters |
| Area Under the Curve (AUC) of ABX464 in Sera | Day 1, Day 28 and Day 84 | Pharmacokinetic parameters |
| Maximum Observed Concentration (Cmax) of ABX464 in Sera | Day 1, Day 28 and day 84 | Pharmacokinetic parameters |
| Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 1, Day 28 and Day 84 | Pharmacokinetics parameters |
| Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 1, Day 28 and Day 84 | Pharmacokinetic parameters |
| Maximum Observed Concentration (Cmax) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 1, Day 28 and Day 84 | Pharmacokinetic parameters |
| Area Under the Curve (AUC) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 1, Day 28 and Day 84 | Pharmacokinetic parameters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD4+ Counts (Cell/mm^3) | Day 28, Day 35, Day 56, Day 84, Day 91 and Day 112 | T-cell determinations |
| Total HIV-1 DNA Reservoir in Peripheral Blood Mononuclear Cells (PBMC) | Day 28, Day 56, Day 84 and Day 112 | HIV reservoir cells (CD4+) |
| Mean Change From Baseline in Plasma Viral Load (Ultrasensitive Assay) | Day 28, Day 56, Day 84 and Day 112 | Viral Load Assessments (HIV-1 RNA copies/ml) |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABX464 150 mg Capsules for 28 Days ABX464 150mg: ABX464 given orally at 150 mg per day from Day 0 to Day 28 (Cohort 1/ HIV infected subjects) | 11 |
| ABX464 50 mg Capsules for 28 Days ABX464 50mg: ABX464 given orally at 50 mg per day from Day 0 to Day 28 (Cohort 2 / non HIV infected subjects) | 12 |
| ABX464 50 mg Capsules for 84 Days ABX464 50mg: ABX464 given orally at 50 mg per day from Day 0 to Day 84 (Cohort 3 / HIV infected subjects) | 13 |
| Total | 36 |
Baseline characteristics
| Characteristic | ABX464 150 mg Capsules for 28 Days | ABX464 50 mg Capsules for 28 Days | ABX464 50 mg Capsules for 84 Days | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 12 Participants | 13 Participants | 36 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 12 Participants | 13 Participants | 36 Participants |
| Region of Enrollment Spain | 11 participants | 12 participants | 13 participants | 36 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 11 Participants | 12 Participants | 13 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 | 0 / 13 |
| other Total, other adverse events | 9 / 11 | 3 / 12 | 7 / 13 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 | 0 / 13 |
Outcome results
Primary
Area Under the Curve (AUC) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC)
Pharmacokinetic parameters
Time frame: Day 1, Day 28 and Day 84
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ABX464 150mg | Area Under the Curve (AUC) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 522.4 ng*h/mL | Geometric Coefficient of Variation 49.2 |
| ABX464 150mg | Area Under the Curve (AUC) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 1 | 1120.7 ng*h/mL | Geometric Coefficient of Variation 52.6 |
| ABX464 50mg for 28 Days | Area Under the Curve (AUC) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 156.0 ng*h/mL | Geometric Coefficient of Variation 51.8 |
| ABX464 50mg for 28 Days | Area Under the Curve (AUC) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 1 | 594.2 ng*h/mL | Geometric Coefficient of Variation 53.2 |
| ABX464 50mg for 84 Days | Area Under the Curve (AUC) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 1 | 481.5 ng*h/mL | Geometric Coefficient of Variation 78.9 |
| ABX464 50mg for 84 Days | Area Under the Curve (AUC) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 84 | 144.9 ng*h/mL | Geometric Coefficient of Variation 48.6 |
| ABX464 50mg for 84 Days | Area Under the Curve (AUC) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 151.6 ng*h/mL | Geometric Coefficient of Variation 74.3 |
Primary
Area Under the Curve (AUC) of ABX464 in Sera
Pharmacokinetic parameters
Time frame: Day 1, Day 28 and Day 84
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ABX464 150mg | Area Under the Curve (AUC) of ABX464 in Sera | Day 28 | 119.8 ng*h/mL | Geometric Coefficient of Variation 48.7 |
| ABX464 150mg | Area Under the Curve (AUC) of ABX464 in Sera | Day 1 | 306.0 ng*h/mL | Geometric Coefficient of Variation 46.5 |
| ABX464 50mg for 28 Days | Area Under the Curve (AUC) of ABX464 in Sera | Day 28 | 17.8 ng*h/mL | Geometric Coefficient of Variation 60.9 |
| ABX464 50mg for 28 Days | Area Under the Curve (AUC) of ABX464 in Sera | Day 1 | 63.7 ng*h/mL | Geometric Coefficient of Variation 39.9 |
| ABX464 50mg for 84 Days | Area Under the Curve (AUC) of ABX464 in Sera | Day 1 | 63.7 ng*h/mL | Geometric Coefficient of Variation 77.4 |
| ABX464 50mg for 84 Days | Area Under the Curve (AUC) of ABX464 in Sera | Day 84 | 28.9 ng*h/mL | Geometric Coefficient of Variation 66.8 |
| ABX464 50mg for 84 Days | Area Under the Curve (AUC) of ABX464 in Sera | Day 28 | 30.3 ng*h/mL | Geometric Coefficient of Variation 68.2 |
Primary
Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC)
Pharmacokinetic parameters
Time frame: Day 1, Day 28 and Day 84
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ABX464 150mg | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 2212.3 ng*h/mL | Geometric Coefficient of Variation 58.8 |
| ABX464 150mg | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 1 | 2133.7 ng*h/mL | Geometric Coefficient of Variation 42.2 |
| ABX464 50mg for 28 Days | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 35.0 ng*h/mL | Geometric Coefficient of Variation 210.1 |
| ABX464 50mg for 28 Days | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 1 | 39.2 ng*h/mL | Geometric Coefficient of Variation 186.7 |
| ABX464 50mg for 84 Days | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 1 | 835.3 ng*h/mL | Geometric Coefficient of Variation 116 |
| ABX464 50mg for 84 Days | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 84 | 766.5 ng*h/mL | Geometric Coefficient of Variation 57.4 |
| ABX464 50mg for 84 Days | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 697.5 ng*h/mL | Geometric Coefficient of Variation 92 |
Primary
Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera
Pharmacokinetics parameters
Time frame: Day 1, Day 28 and Day 84
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ABX464 150mg | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 28 | 48605.0 ng*h/mL | Geometric Coefficient of Variation 40.6 |
| ABX464 150mg | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 1 | 50115.8 ng*h/mL | Geometric Coefficient of Variation 41.5 |
| ABX464 50mg for 28 Days | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 1 | 8282.3 ng*h/mL | Geometric Coefficient of Variation 37 |
| ABX464 50mg for 28 Days | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 28 | 4800.6 ng*h/mL | Geometric Coefficient of Variation 37 |
| ABX464 50mg for 84 Days | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 1 | 11209.6 ng*h/mL | Geometric Coefficient of Variation 66.5 |
| ABX464 50mg for 84 Days | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 28 | 13308.8 ng*h/mL | Geometric Coefficient of Variation 62.5 |
| ABX464 50mg for 84 Days | Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 84 | 14588.2 ng*h/mL | Geometric Coefficient of Variation 58.3 |
Primary
Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint)
Pharmacokinetic parameters
Time frame: Day 1, Day 28, Day 56, Day 84 and Day 112
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABX464 150mg | Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 28 | 0.1 ng/mL | Standard Deviation 0.11 |
| ABX464 150mg | Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 1 | 0.0 ng/mL | Standard Deviation 0 |
| ABX464 150mg | Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 56 | 0.0 ng/mL | Standard Deviation 0 |
| ABX464 50mg for 28 Days | Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 28 | 0.1 ng/mL | Standard Deviation 0.19 |
| ABX464 50mg for 28 Days | Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 1 | 0.0 ng/mL | Standard Deviation 0 |
| ABX464 50mg for 84 Days | Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 28 | 0.1 ng/mL | Standard Deviation 0.13 |
| ABX464 50mg for 84 Days | Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 1 | 0.0 ng/mL | Standard Deviation 0 |
| ABX464 50mg for 84 Days | Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 84 | 0.1 ng/mL | Standard Deviation 0.13 |
| ABX464 50mg for 84 Days | Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 112 | 0.0 ng/mL | Standard Deviation 0 |
Primary
Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint)
Pharmacokinetic parameters
Time frame: Day 1, Day 28, Day 56, Day 84 and Day 112
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABX464 150mg | Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 28 | 0.1 ng/mL | Standard Deviation 0.04 |
| ABX464 150mg | Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 1 | 0.0 ng/mL | Standard Deviation 0 |
| ABX464 150mg | Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 56 | 0.0 ng/mL | Standard Deviation 0 |
| ABX464 50mg for 28 Days | Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 28 | 0.1 ng/mL | Standard Deviation 0.11 |
| ABX464 50mg for 28 Days | Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 1 | 0.1 ng/mL | Standard Deviation 0.08 |
| ABX464 50mg for 84 Days | Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 28 | 0.1 ng/mL | Standard Deviation 0.09 |
| ABX464 50mg for 84 Days | Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 1 | 0.0 ng/mL | Standard Deviation 0 |
| ABX464 50mg for 84 Days | Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 84 | 0.2 ng/mL | Standard Deviation 0.11 |
| ABX464 50mg for 84 Days | Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Day 112 | 0.0 ng/mL | Standard Deviation 0 |
Primary
Maximum Observed Concentration (Cmax) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC)
Pharmacokinetic parameters
Time frame: Day 1, Day 28 and Day 84
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ABX464 150mg | Maximum Observed Concentration (Cmax) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 247.8 ng/mL | Geometric Coefficient of Variation 75.7 |
| ABX464 150mg | Maximum Observed Concentration (Cmax) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 1 | 463.3 ng/mL | Geometric Coefficient of Variation 55 |
| ABX464 50mg for 28 Days | Maximum Observed Concentration (Cmax) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 76.4 ng/mL | Geometric Coefficient of Variation 51.7 |
| ABX464 50mg for 28 Days | Maximum Observed Concentration (Cmax) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 1 | 209.4 ng/mL | Geometric Coefficient of Variation 54.4 |
| ABX464 50mg for 84 Days | Maximum Observed Concentration (Cmax) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 1 | 203.8 ng/mL | Geometric Coefficient of Variation 81 |
| ABX464 50mg for 84 Days | Maximum Observed Concentration (Cmax) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 84 | 73.6 ng/mL | Geometric Coefficient of Variation 57.5 |
| ABX464 50mg for 84 Days | Maximum Observed Concentration (Cmax) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 72.3 ng/mL | Geometric Coefficient of Variation 82.9 |
Primary
Maximum Observed Concentration (Cmax) of ABX464 in Sera
Pharmacokinetic parameters
Time frame: Day 1, Day 28 and day 84
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ABX464 150mg | Maximum Observed Concentration (Cmax) of ABX464 in Sera | Day 28 | 50.9 ng/mL | Geometric Coefficient of Variation 57.1 |
| ABX464 150mg | Maximum Observed Concentration (Cmax) of ABX464 in Sera | Day 1 | 106.1 ng/mL | Geometric Coefficient of Variation 54.5 |
| ABX464 50mg for 28 Days | Maximum Observed Concentration (Cmax) of ABX464 in Sera | Day 28 | 9.3 ng/mL | Geometric Coefficient of Variation 60.3 |
| ABX464 50mg for 28 Days | Maximum Observed Concentration (Cmax) of ABX464 in Sera | Day 1 | 23.1 ng/mL | Geometric Coefficient of Variation 45.2 |
| ABX464 50mg for 84 Days | Maximum Observed Concentration (Cmax) of ABX464 in Sera | Day 1 | 24.5 ng/mL | Geometric Coefficient of Variation 75.5 |
| ABX464 50mg for 84 Days | Maximum Observed Concentration (Cmax) of ABX464 in Sera | Day 84 | 15.6 ng/mL | Geometric Coefficient of Variation 65.6 |
| ABX464 50mg for 84 Days | Maximum Observed Concentration (Cmax) of ABX464 in Sera | Day 28 | 13.0 ng/mL | Geometric Coefficient of Variation 76 |
Primary
Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC)
Pharmacokinetic parameters
Time frame: Day 1, Day 28 and Day 84
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ABX464 150mg | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 491.5 ng/mL | Geometric Coefficient of Variation 73 |
| ABX464 150mg | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 1 | 585.5 ng/mL | Geometric Coefficient of Variation 60.3 |
| ABX464 50mg for 28 Days | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 35.6 ng/mL | Geometric Coefficient of Variation 85.7 |
| ABX464 50mg for 28 Days | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 1 | 39.7 ng/mL | Geometric Coefficient of Variation 90.5 |
| ABX464 50mg for 84 Days | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 1 | 230.0 ng/mL | Geometric Coefficient of Variation 153.9 |
| ABX464 50mg for 84 Days | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 84 | 153.3 ng/mL | Geometric Coefficient of Variation 49.4 |
| ABX464 50mg for 84 Days | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 125.1 ng/mL | Geometric Coefficient of Variation 86.1 |
Primary
Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera
Pharmacokinetic parameters
Time frame: Day 1, Day 28 and Day 84
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ABX464 150mg | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 28 | 7011.1 ng/mL | Geometric Coefficient of Variation 37.5 |
| ABX464 150mg | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 1 | 9918.2 ng/mL | Geometric Coefficient of Variation 33.5 |
| ABX464 50mg for 28 Days | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 28 | 695.9 ng/mL | Geometric Coefficient of Variation 38.6 |
| ABX464 50mg for 28 Days | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 1 | 1626.8 ng/mL | Geometric Coefficient of Variation 36.9 |
| ABX464 50mg for 84 Days | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 1 | 2036.2 ng/mL | Geometric Coefficient of Variation 62.8 |
| ABX464 50mg for 84 Days | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 84 | 2150.6 ng/mL | Geometric Coefficient of Variation 56.1 |
| ABX464 50mg for 84 Days | Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Day 28 | 1705.5 ng/mL | Geometric Coefficient of Variation 71.8 |
Secondary
CD4+ Counts (Cell/mm^3)
T-cell determinations
Time frame: Day 28, Day 35, Day 56, Day 84, Day 91 and Day 112
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data. CD4+ counts measurements were not assessed for cohort 2 subjects as they were HIV non infected subjets.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| ABX464 150mg | CD4+ Counts (Cell/mm^3) | Day 35 | -125.6 cells/mm^3 |
| ABX464 150mg | CD4+ Counts (Cell/mm^3) | Day 28 | -130.6 cells/mm^3 |
| ABX464 150mg | CD4+ Counts (Cell/mm^3) | Day 56 | 29.6 cells/mm^3 |
| ABX464 50mg for 28 Days | CD4+ Counts (Cell/mm^3) | Day 112 | 161.8 cells/mm^3 |
| ABX464 50mg for 28 Days | CD4+ Counts (Cell/mm^3) | Day 91 | 23.3 cells/mm^3 |
| ABX464 50mg for 28 Days | CD4+ Counts (Cell/mm^3) | Day 84 | 8.3 cells/mm^3 |
| ABX464 50mg for 28 Days | CD4+ Counts (Cell/mm^3) | Day 28 | -34.6 cells/mm^3 |
Secondary
Mean Change From Baseline in Plasma Viral Load (Ultrasensitive Assay)
Viral Load Assessments (HIV-1 RNA copies/ml)
Time frame: Day 28, Day 56, Day 84 and Day 112
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data. HIV viral measurements were not assessed for cohort 2 subjects as they were HIV non infected subjets.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| ABX464 150mg | Mean Change From Baseline in Plasma Viral Load (Ultrasensitive Assay) | Day 28 | -0.9 copies/mL |
| ABX464 150mg | Mean Change From Baseline in Plasma Viral Load (Ultrasensitive Assay) | Day 56 | -0.4 copies/mL |
| ABX464 50mg for 28 Days | Mean Change From Baseline in Plasma Viral Load (Ultrasensitive Assay) | Day 28 | -2.0 copies/mL |
| ABX464 50mg for 28 Days | Mean Change From Baseline in Plasma Viral Load (Ultrasensitive Assay) | Day 84 | -0.9 copies/mL |
| ABX464 50mg for 28 Days | Mean Change From Baseline in Plasma Viral Load (Ultrasensitive Assay) | Day 112 | -1.1 copies/mL |
Secondary
Total HIV-1 DNA Reservoir in Peripheral Blood Mononuclear Cells (PBMC)
HIV reservoir cells (CD4+)
Time frame: Day 28, Day 56, Day 84 and Day 112
Population: Subjects who had received at least 1 dose of the Investigational Medicinal Product and who have at least baseline data. Total HIV-1 DNA reservoir measurements were not assessed for cohort 2 subjects as they were HIV non infected subjets.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| ABX464 150mg | Total HIV-1 DNA Reservoir in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | -86.8 copies/10^6 cells |
| ABX464 150mg | Total HIV-1 DNA Reservoir in Peripheral Blood Mononuclear Cells (PBMC) | Day 56 | -37.1 copies/10^6 cells |
| ABX464 50mg for 28 Days | Total HIV-1 DNA Reservoir in Peripheral Blood Mononuclear Cells (PBMC) | Day 112 | 95.6 copies/10^6 cells |
| ABX464 50mg for 28 Days | Total HIV-1 DNA Reservoir in Peripheral Blood Mononuclear Cells (PBMC) | Day 28 | 22.3 copies/10^6 cells |
| ABX464 50mg for 28 Days | Total HIV-1 DNA Reservoir in Peripheral Blood Mononuclear Cells (PBMC) | Day 84 | 10.8 copies/10^6 cells |