HIV-1-infection
Conditions
Brief summary
The goals of this clinical study are to learn more about the study drugs, VRC07-523LS, CAP256V2LS, and vesatolimod (VES) and how safe it is in women that have HIV and are on antiretroviral therapy (ART).
Interventions
DRUGVesatolimod
Administered orally
BIOLOGICALVRC07523LS
Administered intravenously
BIOLOGICALCAP256V2LS
Administered intravenously
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age ≥ 18 years * Females recruited from the Females Rising through Education, Support, and Health (FRESH) acute human immunodeficiency virus (HIV) infection cohort. * Plasma human immunodeficiency -1 (HIV-1) ribonucleic acid (RNA) levels \< 50 copies/mL at the screening visit. * On antiretroviral (ART) regimen for ≥ 12 consecutive months prior to the screening visit. * Have all the following laboratory values at the screening visit: * Hemoglobin ≥ 10.0 g/dL * White blood cells ≥ 2500 cells/μL * Platelets ≥ 125,000/mL * Absolute neutrophil counts ≥ 1000 cells/μL * Cluster of differentiation (CD)4+ T cell count ≥ 500 cells/μL * Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin ≤ 2 × upper limit of normal (ULN) * Creatinine clearance ≥ 60 mL/min * Women of childbearing potential to have documentation of agreement to follow study contraceptive requirements. * Documented plasma HIV-1 RNA \< 50 copies/mL for 12 consecutive months prior to the screening visit. * In the judgment of the investigator, be in good general health. * Documented history of viral sensitivity to VRC07-523LS or CAP256V2LS at the screening visit. Key
Exclusion criteria
* Have poor venous access that limits phlebotomy. * Positive serum pregnancy test. * Nursing participants. * Females with coinfection and/or immunosuppression as described below: * Autoimmune disease requiring ongoing immunosuppression * Evidence of chronic hepatitis B virus (HBV) infection * Evidence of current hepatitis C virus (HCV) infection * Documented history of pre-ART CD4+ T cell count nadir \< 200 cells/μL * History of opportunistic illness indicative of Stage 3 HIV * Acute febrile illness within 4 weeks prior to the first dose * Have current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance or individual's safety. * Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to screening or are expected to receive these agents during the study. * Have previous or current receipt of humanized or human monoclonal antibody (mAbs), or polyclonal immunoglobulin. * Have previous history of an antidrug antibodies response to a therapeutic agent. * Have previous receipt of an HIV vaccine. * Received any vaccine or immunomodulatory medication within 4 weeks prior to screening. * Have a history of any of the following: * Significant serious skin disease * Significant drug sensitivity or drug allergy * Known hypersensitivity to the study drugs, metabolites, or formulation excipients * Previous or current history of bleeding disorder, platelet disorder including unexplained acute or chronic thrombocytopenia * Autoimmune diseases including type 1 diabetes mellitus * Have current Class C acquired immunodeficiency syndrome (AIDS)-defining condition. * Have any serious or active medical or psychiatric illness that would interfere with participants treatment, assessment, or compliance with the protocol. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | Up to 61.1 weeks | An AE is any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. TEAE was defined as any AE that began on or after the study drug start date and no later than last exposure date after permanent discontinuation of study drug, or led to premature study drug discontinuation. |
| Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities | Up to 61.1 weeks | A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the last exposure date after permanent discontinuation of study drug. For maximum postbaseline toxicity grade, the most severe graded abnormality from all tests was counted for each participant. The severity grades were defined by Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities, Antiviral Toxicity Grading Scale, Version 01 April 2015. The CTCAE v5 grading scale was used to grade AEs determined to be cytokine release syndrome and infusion-related reactions. The grading for both scales are as follows: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-Threatening, Grade 5 = Death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Viral Load at the End of ATI | Up to 48 weeks | Baseline value was the last available value collected on or prior to first dose of study drug. |
| Time to ART Resumption Following ATI | Up to 56 weeks | Time to ART resumption (in weeks) = (date of restart ART after ATI period start or censoring date - ATI start date + 1) / 7. |
| Pharmacokinetic (PK) Parameter of VES: Cmax | Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose | Cmax is defined as maximum observed concentration of drug. |
| PK Parameter of VES: Tmax | Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose | Tmax is defined as time (observed time point) of Cmax. |
| PK Parameter of VES: Clast | Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose | Clast is defined as last observed quantifiable concentration of the drug. |
| PK Parameter of VES: Tlast | Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose | Tlast is defined as time (observed time point) of Clast. |
| PK Parameter of VES: AUCinf | Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose | AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz). |
| PK Parameter of VES: AUClast | Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. |
| PK Parameter of VES: AUCexp | Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose | AUCexp is defined as AUC extrapolated between AUClast and AUCinf. |
| PK Parameter of VES: t1/2 | Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose | t1/2 is defined as estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 2 by the terminal elimination rate constant (λz). |
| PK Parameter of VES: CL/F | Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose | CL/F is defined as apparent clearance following extravascular administration. |
| PK Parameter of VES: Vz/F | Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose | Vz/F is defined as apparent volume of distribution during the terminal phase following extravascular administration. |
| PK Parameter of VRC07-523LS: Cmax | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | Cmax is defined as maximum observed concentration of drug. |
| PK Parameter of VRC07-523LS: Tmax | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | Tmax is defined as time (observed time point) of Cmax. |
| PK Parameter of VRC07-523LS: Clast | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | Clast is defined as last observed quantifiable concentration of the drug. |
| PK Parameter of VRC07-523LS: Tlast | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | Tlast is defined as time (observed time point) of Clast. |
| PK Parameter of VRC07-523LS: AUCinf | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz). |
| PK Parameter of VRC07-523LS: AUClast | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. |
| Time to Viral Rebound (Confirmed ≥ 50 Copies/mL and ≥ 200 Copies/mL) Following ATI | Up to 56 weeks | Virologic rebound is defined as at any visit a rebound in HIV-1 RNA to ≥ 50 copies/mL or ≥ 200 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled visit. Time to rebound (in weeks) = (date of rebound or censoring date - ATI start date + 1) / 7. |
| PK Parameter of VRC07-523LS: t1/2 | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | t1/2 is defined as estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 2 by the terminal elimination rate constant (λz). |
| PK Parameter of VRC07-523LS: Clearance (CL) | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | CL is defined as clearance following intravenous administration. |
| PK Parameter of VRC07-523LS: Vss | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | Vss is defined as the volume of distribution at steady-state following intravenous administration. |
| PK Parameter of VRC07-523LS: Vz | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | Vz is defined as volume of distribution of the drug during the terminal phase after intravenous administration. |
| PK Parameter of CAP256V2LS: Cmax | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | Cmax is defined as maximum observed concentration of drug. |
| PK Parameter of CAP256V2LS: Tmax | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | Tmax is defined as time (observed time point) of Cmax. |
| PK Parameter of CAP256V2LS: Clast | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | Clast is defined as last observed quantifiable concentration of the drug. |
| PK Parameter of CAP256V2LS: Tlast | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | Tlast is defined as time (observed time point) of Clast. |
| PK Parameter of CAP256V2LS: AUCinf | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz). |
| PK Parameter of CAP256V2LS: AUClast | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. |
| PK Parameter of CAP256V2LS: AUCexp | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | AUCexp is defined as AUC extrapolated between AUClast and AUCinf. |
| PK Parameter of CAP256V2LS: t1/2 | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | t1/2 is defined as estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 2 by the terminal elimination rate constant (λz). |
| PK Parameter of CAP256V2LS: CL | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | CL is defined as clearance following intravenous administration. |
| PK Parameter of CAP256V2LS: Vz | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | Vz is defined as volume of distribution of the drug during the terminal phase after intravenous administration. |
| PK Parameter of CAP256V2LS: Vss | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | Vss is defined as the volume of distribution at steady-state after intravenous administration. |
| Percentage of Participants With Treatment-emergent Positive Anti-VRC07-523LS Antibodies | Prebaseline (Day -13) up to Day 413 | — |
| Percentage of Participants With Treatment-emergent Positive Anti-CAP256V2LS Antibodies | Prebaseline (Day -13) up to Day 413 | — |
| PK Parameter of VRC07-523LS: AUCexp | Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413 | AUCexp is defined as AUC extrapolated between AUClast and AUCinf. |
| Change in Plasma Viral Load Set-point Following ATI | Pre-ART (Screening) and prior to ART reinitiation following ATI (Up to 56 weeks) | Change in plasma viral load set-point between pre-ART value and prior to ART reinitiation following ATI was summarized. The pre-ART set point value is the HIV-RNA load count prior to start of initial ARV treatment recorded in the clinical database. |
Countries
South Africa
Participant flow
Recruitment details
Participants were enrolled at a study site in South Africa.
Pre-assignment details
26 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| VRC07-523LS + CAP256V2LS + Vesatolimod (VES) In Period 1 (Days 0 to 28), participants received ART through Period. On Days 0 and 14, participants were administered VES 6mg orally and on Day 28, participants were administered VES either 6mg or 8mg orally. VRC07-523LS 20mg/kg & CAP256V2LS 20mg/kg were administered intravenously on Day 7. In Period 2 (Days 29 to 133 or until ART restart), participants discontinued ART at Day 35 and remained off ART until reaching ART restart criteria. Participants received VES 8mg orally every 2 weeks from Day 29 or until plasma HIV-1 RNA was \>=5000 copies/mL. In Period 3, (Days 134 to 336 or until ART restart), participants continued ATI and no study treatment was administered. In Period 4, (Days 337 to 413) participants who had not met ART restart criteria by Day 337 either choose to restart ART (Period 4a) or choose to continue ATI until end of study (Period 4B). Any participants who met ART restart criteria before the end of the study remained in follow-up on ART (Period 4A). | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | VRC07-523LS + CAP256V2LS + Vesatolimod (VES) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 27 years STANDARD_DEVIATION 2.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 0 Participants |
| Region of Enrollment South Africa | 20 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 19 / 20 |
| serious Total, serious adverse events | 2 / 20 |
Outcome results
Primary
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
An AE is any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. TEAE was defined as any AE that began on or after the study drug start date and no later than last exposure date after permanent discontinuation of study drug, or led to premature study drug discontinuation.
Time frame: Up to 61.1 weeks
Population: The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 95 percentage of participants |
Primary
Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities
A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the last exposure date after permanent discontinuation of study drug. For maximum postbaseline toxicity grade, the most severe graded abnormality from all tests was counted for each participant. The severity grades were defined by Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities, Antiviral Toxicity Grading Scale, Version 01 April 2015. The CTCAE v5 grading scale was used to grade AEs determined to be cytokine release syndrome and infusion-related reactions. The grading for both scales are as follows: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-Threatening, Grade 5 = Death.
Time frame: Up to 61.1 weeks
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities | Any Grade 1 or Higher | 95 percentage of participants |
| VRC07-523LS + CAP256V2LS + VES | Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities | Grade 1 | 20 percentage of participants |
| VRC07-523LS + CAP256V2LS + VES | Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities | Grade 2 | 40 percentage of participants |
| VRC07-523LS + CAP256V2LS + VES | Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities | Grade 3 | 35 percentage of participants |
| VRC07-523LS + CAP256V2LS + VES | Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities | Grade 4 | 0 percentage of participants |
Secondary
Change From Baseline of Viral Load at the End of ATI
Baseline value was the last available value collected on or prior to first dose of study drug.
Time frame: Up to 48 weeks
Population: Participants in Full Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | Change From Baseline of Viral Load at the End of ATI | 2.96 log10 copies/mL |
Secondary
Change in Plasma Viral Load Set-point Following ATI
Change in plasma viral load set-point between pre-ART value and prior to ART reinitiation following ATI was summarized. The pre-ART set point value is the HIV-RNA load count prior to start of initial ARV treatment recorded in the clinical database.
Time frame: Pre-ART (Screening) and prior to ART reinitiation following ATI (Up to 56 weeks)
Population: Participants in Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | Change in Plasma Viral Load Set-point Following ATI | -1.42 log10 copies/mL |
Comparison: The comparison was between plasma viral HIV-1 RNA data at set-point and at pre-ART within the same treatment group.p-value: 0.002Wilcoxon signed rank test
Secondary
Percentage of Participants With Treatment-emergent Positive Anti-CAP256V2LS Antibodies
Time frame: Prebaseline (Day -13) up to Day 413
Population: The CAP256V2LS Immunogenicity Analysis Set included all enrolled participants who received at least 1 dose of CAP256V2LS and have had at least 1 nonmissing value for the immunogenicity evaluation of interest (ie, anti-CAP256V2LS antibody).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | Percentage of Participants With Treatment-emergent Positive Anti-CAP256V2LS Antibodies | 55 percentage of participants |
Secondary
Percentage of Participants With Treatment-emergent Positive Anti-VRC07-523LS Antibodies
Time frame: Prebaseline (Day -13) up to Day 413
Population: The VRC07-523LS Immunogenicity Analysis Set included all enrolled participants who received at least 1 dose of VRC07-523LS and have had at least 1 nonmissing value for the immunogenicity evaluation of interest (ie, anti-VRC07-523LS antibody).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | Percentage of Participants With Treatment-emergent Positive Anti-VRC07-523LS Antibodies | 15.0 percentage of participants |
Secondary
Pharmacokinetic (PK) Parameter of VES: Cmax
Cmax is defined as maximum observed concentration of drug.
Time frame: Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
Population: The VES PK Analysis Set included all participants who were enrolled and had received at least 1 dose of VES and for whom PK concentrations of analyte VES were available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | Pharmacokinetic (PK) Parameter of VES: Cmax | 6350 pg/mL | Standard Deviation 4220 |
Secondary
PK Parameter of CAP256V2LS: AUCexp
AUCexp is defined as AUC extrapolated between AUClast and AUCinf.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in CAP256V2LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of CAP256V2LS: AUCexp | 1.58 percent | Standard Deviation 0.452 |
Secondary
PK Parameter of CAP256V2LS: AUCinf
AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz).
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in CAP256V2LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of CAP256V2LS: AUCinf | 4290 day*µg/mL | Standard Deviation 729 |
Secondary
PK Parameter of CAP256V2LS: AUClast
AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in CAP256V2LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of CAP256V2LS: AUClast | 4230 day*µg/mL | Standard Deviation 710 |
Secondary
PK Parameter of CAP256V2LS: CL
CL is defined as clearance following intravenous administration.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in CAP256V2LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of CAP256V2LS: CL | 0.352 L/day | Standard Deviation 0.116 |
Secondary
PK Parameter of CAP256V2LS: Clast
Clast is defined as last observed quantifiable concentration of the drug.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in CAP256V2LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of CAP256V2LS: Clast | 1.52 µg/mL | Standard Deviation 0.493 |
Secondary
PK Parameter of CAP256V2LS: Cmax
Cmax is defined as maximum observed concentration of drug.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: The CAP256V2LS PK Analysis Set included all participants who were enrolled and had received at least 1 dose of CAP256V2LS and for whom PK concentrations of analyte CAP256V2LS were available. Participants in CAP256V2LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of CAP256V2LS: Cmax | 644 µg/mL | Standard Deviation 309 |
Secondary
PK Parameter of CAP256V2LS: t1/2
t1/2 is defined as estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 2 by the terminal elimination rate constant (λz).
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in CAP256V2LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of CAP256V2LS: t1/2 | 31.4 day |
Secondary
PK Parameter of CAP256V2LS: Tlast
Tlast is defined as time (observed time point) of Clast.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in CAP256V2LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of CAP256V2LS: Tlast | 172 day |
Secondary
PK Parameter of CAP256V2LS: Tmax
Tmax is defined as time (observed time point) of Cmax.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in CAP256V2LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of CAP256V2LS: Tmax | 1.50 h |
Secondary
PK Parameter of CAP256V2LS: Vss
Vss is defined as the volume of distribution at steady-state after intravenous administration.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in CAP256V2LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of CAP256V2LS: Vss | 10.6 L | Standard Deviation 2.21 |
Secondary
PK Parameter of CAP256V2LS: Vz
Vz is defined as volume of distribution of the drug during the terminal phase after intravenous administration.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in CAP256V2LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of CAP256V2LS: Vz | 15.3 L | Standard Deviation 3.72 |
Secondary
PK Parameter of VES: AUCexp
AUCexp is defined as AUC extrapolated between AUClast and AUCinf.
Time frame: Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
Population: Participants in VES PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VES: AUCexp | 12.4 percent | Standard Deviation 6.68 |
Secondary
PK Parameter of VES: AUCinf
AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz).
Time frame: Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
Population: Participants in VES analysis set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VES: AUCinf | 62700 h*pg/mL | Standard Deviation 37700 |
Secondary
PK Parameter of VES: AUClast
AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.
Time frame: Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
Population: Participants in VES analysis set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VES: AUClast | 55500 h*pg/mL | Standard Deviation 34200 |
Secondary
PK Parameter of VES: Clast
Clast is defined as last observed quantifiable concentration of the drug.
Time frame: Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
Population: Participants in VES PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VES: Clast | 279 pg/mL | Standard Deviation 177 |
Secondary
PK Parameter of VES: CL/F
CL/F is defined as apparent clearance following extravascular administration.
Time frame: Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
Population: Participants in VES PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VES: CL/F | 144 Liters (L)/h | Standard Deviation 112 |
Secondary
PK Parameter of VES: t1/2
t1/2 is defined as estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 2 by the terminal elimination rate constant (λz).
Time frame: Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
Population: Participants in VES PK Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VES: t1/2 | 15.9 h |
Secondary
PK Parameter of VES: Tlast
Tlast is defined as time (observed time point) of Clast.
Time frame: Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
Population: Participants in VES PK Analysis Set were anlayzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VES: Tlast | 48.0 h |
Secondary
PK Parameter of VES: Tmax
Tmax is defined as time (observed time point) of Cmax.
Time frame: Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
Population: Participants in VES PK Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VES: Tmax | 2.00 hours (h) |
Secondary
PK Parameter of VES: Vz/F
Vz/F is defined as apparent volume of distribution during the terminal phase following extravascular administration.
Time frame: Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
Population: Participants with VES PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VES: Vz/F | 3810 L | Standard Deviation 3650 |
Secondary
PK Parameter of VRC07-523LS: AUCexp
AUCexp is defined as AUC extrapolated between AUClast and AUCinf.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in VRC07-523LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VRC07-523LS: AUCexp | 2.94 percent | Standard Deviation 2.71 |
Secondary
PK Parameter of VRC07-523LS: AUCinf
AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz).
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in VRC07-523LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VRC07-523LS: AUCinf | 7540 day*µg/mL | Standard Deviation 1360 |
Secondary
PK Parameter of VRC07-523LS: AUClast
AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in VRC07-523LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VRC07-523LS: AUClast | 7320 day*µg/mL | Standard Deviation 1340 |
Secondary
PK Parameter of VRC07-523LS: Clast
Clast is defined as last observed quantifiable concentration of the drug.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in VRC07-523LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VRC07-523LS: Clast | 3.51 µg/mL | Standard Deviation 2.98 |
Secondary
PK Parameter of VRC07-523LS: Clearance (CL)
CL is defined as clearance following intravenous administration.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in VRC07-523LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VRC07-523LS: Clearance (CL) | 0.198 L/day | Standard Deviation 0.0513 |
Secondary
PK Parameter of VRC07-523LS: Cmax
Cmax is defined as maximum observed concentration of drug.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: The VRC07-523LS PK Analysis Set included all participants who were enrolled and had received at least 1 dose of VRC07-523LS and for whom PK concentrations of analyte VRC07-523LS were available. Participants in VRC07-523LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VRC07-523LS: Cmax | 481 µg/mL | Standard Deviation 83.5 |
Secondary
PK Parameter of VRC07-523LS: t1/2
t1/2 is defined as estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 2 by the terminal elimination rate constant (λz).
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in VRC07-523LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VRC07-523LS: t1/2 | 41.9 day |
Secondary
PK Parameter of VRC07-523LS: Tlast
Tlast is defined as time (observed time point) of Clast.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in VRC07-523LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VRC07-523LS: Tlast | 238 day |
Secondary
PK Parameter of VRC07-523LS: Tmax
Tmax is defined as time (observed time point) of Cmax.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in VRC07-523LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VRC07-523LS: Tmax | 0.550 h |
Secondary
PK Parameter of VRC07-523LS: Vss
Vss is defined as the volume of distribution at steady-state following intravenous administration.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in VRC07-523LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VRC07-523LS: Vss | 11.5 L | Standard Error 2.54 |
Secondary
PK Parameter of VRC07-523LS: Vz
Vz is defined as volume of distribution of the drug during the terminal phase after intravenous administration.
Time frame: Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Population: Participants in VRC07-523LS PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | PK Parameter of VRC07-523LS: Vz | 12.0 L | Standard Deviation 3.96 |
Secondary
Time to ART Resumption Following ATI
Time to ART resumption (in weeks) = (date of restart ART after ATI period start or censoring date - ATI start date + 1) / 7.
Time frame: Up to 56 weeks
Population: Participants in full analysis set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | Time to ART Resumption Following ATI | 24.21 weeks |
Secondary
Time to Viral Rebound (Confirmed ≥ 50 Copies/mL and ≥ 200 Copies/mL) Following ATI
Virologic rebound is defined as at any visit a rebound in HIV-1 RNA to ≥ 50 copies/mL or ≥ 200 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled visit. Time to rebound (in weeks) = (date of rebound or censoring date - ATI start date + 1) / 7.
Time frame: Up to 56 weeks
Population: The Full Analysis Set included all participants who were enrolled into the study and had received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| VRC07-523LS + CAP256V2LS + VES | Time to Viral Rebound (Confirmed ≥ 50 Copies/mL and ≥ 200 Copies/mL) Following ATI | Confirmed ≥ 50 copies/mL | 11.00 weeks |
| VRC07-523LS + CAP256V2LS + VES | Time to Viral Rebound (Confirmed ≥ 50 Copies/mL and ≥ 200 Copies/mL) Following ATI | Confirmed ≥ 200 copies/mL | 11.00 weeks |