HIV-1 Infection
Conditions
Brief summary
The primary objective of this study is to evaluate the safety and tolerability of a combination of the broadly neutralizing antibodies (bNAbs) teropavimab (formerly GS-5423) and zinlirvimab (formerly GS-2872) in combination with the HIV capsid inhibitor lenacapavir (LEN).
Interventions
DRUGOral Lenacapavir
Tablets administered without regard to food
Administered in the abdomen via subcutaneous injections
DRUGTeropavimab
Administered intravenously
DRUGZinlirvimab
Administered intravenously
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Clinical pharmacologist and sponsor are not masked to treatment assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * On first-line antiretroviral therapy (ART) for ≥ 2 years prior to screening. A change in ART regimen ≥ 28 days prior to screening for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed * No documented historical resistance to the current ART regimen * Plasma HIV-1 RNA \< 50 copies/mL at screening * Documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 18 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or blip) prior to screening are acceptable. * Proviral phenotypic sensitivity to both teropavimab and zinlirvimab at screening by the PhenoSense mAb Assay (Monogram Biosciences) for inclusion in the Primary Cohort; sensitivity at screening by the PhenoSense mAb Assay (Monogram Biosciences) to 1 mAb, either teropavimab or zinlirvimab, within 18 months prior to enrollment for inclusion in the optional Pilot Cohort \-- In both cohorts, teropavimab sensitivity is defined as 90% inhibitory concentration (IC90) ≤ 2 μg/mL; zinlirvimab sensitivity is defined as IC90 ≤ 2 μg/mL; * Cluster determinant 4+ (CD4+) count nadir ≥ 350 cells/μL * Screening CD4+ count ≥ 500 cells/μL * Availability of a fully active alternative ART regimen, in the opinion of the investigator, in the event of discontinuation of the current ART regimen with development of resistance Key
Exclusion criteria
* Comorbid condition requiring ongoing immunosuppression * Evidence of current hepatitis B virus (HBV) infection * Evidence of current hepatitis C virus (HCV) infection (prior infection cleared spontaneously or with treatment is acceptable) * History of opportunistic infection or illness indicative of Stage 3 HIV disease Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) | Day 1 up to Week 26 | A treatment emergent SAE was defined as an event that, at any dose, resulted in the following: death; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly/birth defect; a medically important event or reaction: such events may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes constituting SAEs. These events had an onset date on or after the study drug start date and prior to the last exposure date of long-acting (LA) regimen period for the LA regimen period analysis. The long acting regimen period included participants who were randomized and received at least one dose of the complete LA study drug regimen (ie, SC LEN + Teropavimab + Zinlirvimab). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Primary Cohort: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm | Week 26 | The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 was analyzed using the snapshot algorithm, which defined a participant's virologic outcome and included participants a) who had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 26 analysis window; b) who did not have on-treatment HIV-1 RNA data in the Week 26 analysis window and i) discontinued study drug prior to or in the Week 26 analysis window due to lack of efficacy, or ii) discontinued study drug prior to or in the Week 26 analysis window due to AE or death and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or iii) discontinued study drug prior to or in the Week 26 analysis window due to reasons other than AE, death, or lack of efficacy and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL. Week 26 window was between Days 176 and 224 (inclusive). |
| Primary Cohort: Percentage of Participants With Positive Anti-Teropavimab Antibodies | Week 26 | Anti-teropavimab antibodies positive participants are participants with positive treatment-emergent anti-drug antibody. |
| Primary Cohort: Percentage of Participants With Positive Anti-zinlirvimab Antibodies | Week 26 | Anti-zinlirvimab antibodies positive participants are participants with positive treatment-emergent anti-drug antibody. |
| Primary Cohort: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 26 | Baseline; Week 26 | — |
| Primary Cohort: Number of Participants Who Develop Treatment-Emergent Resistance to LEN, Teropavimab, and Zinlirvimab | Day 1 up to Week 26 | Participants in the Resistance Analysis Population analyzed for this outcome included any participant who had received 1 dose of study drug, maintained their study drug regimen, and met one of the following virologic failure criteria: * Participants with HIV-1 RNA \>/= 200 copies/mL on 2 consecutive visits * Participants with HIV-1 RNA \>/= 200 copies/mL at study discontinuation or Week 26. |
| Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | Day 1 up to Week 26 | TEAEs were those adverse events that began on or after the first dose date of study drug and prior to last exposure date of LA regimen from participants who prematurely discontinued study or completed study, or any adverse events led to premature study drug discontinuation. |
| Primary Cohort: Pharmacokinetic (PK) Parameter: AUC0-26 of Teropavimab | Predose and at End of Infusion (EOI) of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26 | AUC0-26 is defined as the concentration of drug over time from Week zero to Week 26. |
| Primary Cohort: PK Parameter: AUC0-26 of Zinlirvimab | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26 | AUC0-26 is defined as the concentration of drug over time from Week zero to Week 26. |
| Primary Cohort: PK Parameter: AUClast of Teropavimab | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) | AUClast is defined as the concentration of drug from time zero to the last observable concentration. |
| Primary Cohort: PK Parameter: AUClast of Zinlirvimab | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) | AUClast is defined as the concentration of drug from time zero to the last observable concentration. |
| Primary Cohort: PK Parameter: T1/2 of LEN | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) | T1/2 is defined as the estimate of the terminal elimination half-life of the drug. |
| Primary Cohort: Percentage of Participants With Human Immunodeficiency Virus- 1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 26 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm | Week 26 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 26 was analyzed using the snapshot algorithm, which defined a participant's virologic outcome and included participants who had the last available on-treatment HIV-1 RNA \< 50 copies/mL in the Week 26 analysis window. Week 26 window was between Days 176 and 224 (inclusive). |
| Primary Cohort: PK Parameter: T1/2 of Zinlirvimab | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) | T1/2 is defined as the estimate of the terminal elimination half-life of the drug. |
| Primary Cohort: PK Parameter: Cmax of Teropavimab | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) | Cmax is defined as the maximum observed concentration of drug. |
| Primary Cohort: PK Parameter: Cmax of Zinlirvimab | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) | Cmax is defined as the maximum observed concentration of drug. |
| Primary Cohort: PK Parameter: Tmax of Teropavimab | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) | Tmax is defined as the time (observed time point) of Cmax. |
| Primary Cohort: PK Parameter: Tmax of Zinlirvimab | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) | Tmax is defined as the time (observed time point) of Cmax. |
| Primary Cohort: PK Parameter: Tlast of LEN | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) | Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug). |
| Primary Cohort: PK Parameter: Tlast of Teropavimab | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) | Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug). |
| Primary Cohort: PK Parameter: Tlast of Zinlirvimab | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) | Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug). |
| Primary Cohort: PK Parameter: C26week of LEN | Week 26 | C26week is the concentration at week 26. |
| Primary Cohort: PK Parameter: C26week of Teropavimab | Week 26 | C26week is the concentration at week 26. |
| Primary Cohort: PK Parameter: C26week of Zinlirvimab | Week 26 | C26week is the concentration at week 26. |
| Primary Cohort: PK Parameter: T1/2 of Teropavimab | Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) | T1/2 is defined as the estimate of the terminal elimination half-life of the drug. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States.
Pre-assignment details
124 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg Participants received a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants received 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1. | 11 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg Participants received a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants received 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1. | 10 |
| Pilot Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg Participants received a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants received 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1. | 5 |
| Pilot Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg Participants received a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants received 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1. | 6 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 | 0 | 0 |
| Overall Study | Withdrew consent | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Pilot Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Pilot Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 10 Participants | 5 Participants | 6 Participants | 32 Participants |
| Age, Continuous | 45 years STANDARD_DEVIATION 9.8 | 41 years STANDARD_DEVIATION 11.1 | 47 years STANDARD_DEVIATION 15.1 | 46 years STANDARD_DEVIATION 11.4 | 44 years STANDARD_DEVIATION 11.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 3 Participants | 2 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 7 Participants | 3 Participants | 5 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Race Other or More Than One Race | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Race White | 7 Participants | 5 Participants | 3 Participants | 3 Participants | 18 Participants |
| Region of Enrollment United States | 11 Participants | 10 Participants | 5 Participants | 6 Participants | 32 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 2 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 3 Participants | 5 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 9 / 11 | 10 / 10 | 4 / 5 | 5 / 6 |
| serious Total, serious adverse events | 2 / 11 | 0 / 10 | 1 / 5 | 0 / 6 |
Outcome results
Primary
Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)
A treatment emergent SAE was defined as an event that, at any dose, resulted in the following: death; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly/birth defect; a medically important event or reaction: such events may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes constituting SAEs. These events had an onset date on or after the study drug start date and prior to the last exposure date of long-acting (LA) regimen period for the LA regimen period analysis. The long acting regimen period included participants who were randomized and received at least one dose of the complete LA study drug regimen (ie, SC LEN + Teropavimab + Zinlirvimab).
Time frame: Day 1 up to Week 26
Population: The Safety Analysis Set for the LA regimen included all randomized participants who had received at least 1 dose of the complete LA study drug regimen (ie, SC LEN + Teropavimab + Zinlirvimab).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) | 0 percentage of participants |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) | 0 percentage of participants |
Secondary
Primary Cohort: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 26
Time frame: Baseline; Week 26
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 26 | Baseline | 903 cells per microliter (cells/µL) | Standard Deviation 303.7 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 26 | Week 26 | -25 cells per microliter (cells/µL) | Standard Deviation 241.6 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 26 | Baseline | 1086 cells per microliter (cells/µL) | Standard Deviation 333.6 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 26 | Week 26 | -5 cells per microliter (cells/µL) | Standard Deviation 162.2 |
Secondary
Primary Cohort: Number of Participants Who Develop Treatment-Emergent Resistance to LEN, Teropavimab, and Zinlirvimab
Participants in the Resistance Analysis Population analyzed for this outcome included any participant who had received 1 dose of study drug, maintained their study drug regimen, and met one of the following virologic failure criteria: * Participants with HIV-1 RNA \>/= 200 copies/mL on 2 consecutive visits * Participants with HIV-1 RNA \>/= 200 copies/mL at study discontinuation or Week 26.
Time frame: Day 1 up to Week 26
Population: Participants in the Resistance Analysis Population included those who experienced virologic failure through Week 26.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: Number of Participants Who Develop Treatment-Emergent Resistance to LEN, Teropavimab, and Zinlirvimab | Participants who developed resistance to LEN | 1 Participants |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: Number of Participants Who Develop Treatment-Emergent Resistance to LEN, Teropavimab, and Zinlirvimab | Participants who developed resistance to Teropavimab | 0 Participants |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: Number of Participants Who Develop Treatment-Emergent Resistance to LEN, Teropavimab, and Zinlirvimab | Participants who developed resistance to Zinlirvimab | 0 Participants |
Secondary
Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
TEAEs were those adverse events that began on or after the first dose date of study drug and prior to last exposure date of LA regimen from participants who prematurely discontinued study or completed study, or any adverse events led to premature study drug discontinuation.
Time frame: Day 1 up to Week 26
Population: Participants in the Safety Analysis Set for the LA regimen were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | 90 percentage of participants |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | 100 percentage of participants |
Secondary
Primary Cohort: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 was analyzed using the snapshot algorithm, which defined a participant's virologic outcome and included participants a) who had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 26 analysis window; b) who did not have on-treatment HIV-1 RNA data in the Week 26 analysis window and i) discontinued study drug prior to or in the Week 26 analysis window due to lack of efficacy, or ii) discontinued study drug prior to or in the Week 26 analysis window due to AE or death and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or iii) discontinued study drug prior to or in the Week 26 analysis window due to reasons other than AE, death, or lack of efficacy and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL. Week 26 window was between Days 176 and 224 (inclusive).
Time frame: Week 26
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm | 10.0 percentage of participants |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm | 0 percentage of participants |
Secondary
Primary Cohort: Percentage of Participants With Human Immunodeficiency Virus- 1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 26 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 26 was analyzed using the snapshot algorithm, which defined a participant's virologic outcome and included participants who had the last available on-treatment HIV-1 RNA \< 50 copies/mL in the Week 26 analysis window. Week 26 window was between Days 176 and 224 (inclusive).
Time frame: Week 26
Population: The Full Analysis Set included all randomized participants who had received at least 1 dose of the complete LA study drug regimen (ie, SC LEN + Teropavimab + Zinlirvimab) without major protocol violation (defined as meeting exclusion criterion of having chronic hepatitis B virus infection).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: Percentage of Participants With Human Immunodeficiency Virus- 1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 26 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm | 90.0 percentage of participants |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: Percentage of Participants With Human Immunodeficiency Virus- 1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 26 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm | 90.0 percentage of participants |
Secondary
Primary Cohort: Percentage of Participants With Positive Anti-Teropavimab Antibodies
Anti-teropavimab antibodies positive participants are participants with positive treatment-emergent anti-drug antibody.
Time frame: Week 26
Population: Anti-teropavimab Immunogenicity Analysis Set included all randomized participants who had received at least 1 dose of study drug and have had at least 1 nonmissing value for anti-teropavimab evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: Percentage of Participants With Positive Anti-Teropavimab Antibodies | 50.0 percentage of participants |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: Percentage of Participants With Positive Anti-Teropavimab Antibodies | 10.0 percentage of participants |
Secondary
Primary Cohort: Percentage of Participants With Positive Anti-zinlirvimab Antibodies
Anti-zinlirvimab antibodies positive participants are participants with positive treatment-emergent anti-drug antibody.
Time frame: Week 26
Population: Anti-zinlirvimab Immunogenicity Analysis Set included all randomized participants who had received at least 1 dose of study drug and have had at least 1 nonmissing value for anti- zinlirvimab evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: Percentage of Participants With Positive Anti-zinlirvimab Antibodies | 40.0 percentage of participants |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: Percentage of Participants With Positive Anti-zinlirvimab Antibodies | 20.0 percentage of participants |
Secondary
Primary Cohort: Pharmacokinetic (PK) Parameter: AUC0-26 of Teropavimab
AUC0-26 is defined as the concentration of drug over time from Week zero to Week 26.
Time frame: Predose and at End of Infusion (EOI) of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26
Population: The Teropavimab PK Analysis Set included all randomized participants who had received at least 1 dose of study drug, and had at least 1 nonmissing teropavimab concentration value reported by the PK laboratory test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: Pharmacokinetic (PK) Parameter: AUC0-26 of Teropavimab | 30500 day* μg/mL | Standard Deviation 2270 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: Pharmacokinetic (PK) Parameter: AUC0-26 of Teropavimab | 31600 day* μg/mL | Standard Deviation 3750 |
Secondary
Primary Cohort: PK Parameter: AUC0-26 of Zinlirvimab
AUC0-26 is defined as the concentration of drug over time from Week zero to Week 26.
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26
Population: The Zinlirvimab PK Analysis Set included all randomized participants who had received at least 1 dose of study drug, and had at least 1 nonmissing zinlirvimab concentration value reported by the PK laboratory test. Participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: AUC0-26 of Zinlirvimab | 14800 day* μg/mL | Standard Deviation 2090 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: AUC0-26 of Zinlirvimab | 46100 day* μg/mL | Standard Deviation 4180 |
Secondary
Primary Cohort: PK Parameter: AUClast of Teropavimab
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Population: Participants in the Teropavimab PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: AUClast of Teropavimab | 32900 day* μg/mL | Standard Deviation 3140 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: AUClast of Teropavimab | 34400 day* μg/mL | Standard Deviation 5500 |
Secondary
Primary Cohort: PK Parameter: AUClast of Zinlirvimab
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Population: Participants in the Zinlirvimab PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: AUClast of Zinlirvimab | 17100 day* μg/mL | Standard Deviation 2640 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: AUClast of Zinlirvimab | 54700 day* μg/mL | Standard Deviation 5290 |
Secondary
Primary Cohort: PK Parameter: C26week of LEN
C26week is the concentration at week 26.
Time frame: Week 26
Population: Participants in the LEN PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: C26week of LEN | 27.2 ng/mL | Standard Deviation 17.4 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: C26week of LEN | 22.5 ng/mL | Standard Deviation 17 |
Secondary
Primary Cohort: PK Parameter: C26week of Teropavimab
C26week is the concentration at week 26.
Time frame: Week 26
Population: Participants in the Teropavimab PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: C26week of Teropavimab | 38.4 μg/mL | Standard Deviation 5.89 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: C26week of Teropavimab | 42.7 μg/mL | Standard Deviation 6.49 |
Secondary
Primary Cohort: PK Parameter: C26week of Zinlirvimab
C26week is the concentration at week 26.
Time frame: Week 26
Population: Participants in the Zinlirvimab PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: C26week of Zinlirvimab | 27.2 μg/mL | Standard Deviation 6.44 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: C26week of Zinlirvimab | 84.6 μg/mL | Standard Deviation 27.1 |
Secondary
Primary Cohort: PK Parameter: Cmax of Teropavimab
Cmax is defined as the maximum observed concentration of drug.
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Population: Participants in the Teropavimab PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: Cmax of Teropavimab | 1090 μg/mL | Standard Deviation 160 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: Cmax of Teropavimab | 1090 μg/mL | Standard Deviation 222 |
Secondary
Primary Cohort: PK Parameter: Cmax of Zinlirvimab
Cmax is defined as the maximum observed concentration of drug.
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Population: Participants in the Zinlirvimab PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: Cmax of Zinlirvimab | 378 μg/mL | Standard Deviation 57.5 |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: Cmax of Zinlirvimab | 1110 μg/mL | Standard Deviation 187 |
Secondary
Primary Cohort: PK Parameter: T1/2 of LEN
T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Population: The LEN PK Analysis Set included all randomized participants who had received at least 1 dose of study drug, and had at least 1 nonmissing LEN concentration value reported by the PK laboratory test. Participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: T1/2 of LEN | 65.8 day |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: T1/2 of LEN | 69.8 day |
Secondary
Primary Cohort: PK Parameter: T1/2 of Teropavimab
T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Population: Participants in the Teropavimab PK Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: T1/2 of Teropavimab | 65.2 day |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: T1/2 of Teropavimab | 70.5 day |
Secondary
Primary Cohort: PK Parameter: T1/2 of Zinlirvimab
T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Population: Participants in the Zinlirvimab PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: T1/2 of Zinlirvimab | 76.7 day |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: T1/2 of Zinlirvimab | 84.5 day |
Secondary
Primary Cohort: PK Parameter: Tlast of LEN
Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Population: Participants in the LEN PK Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: Tlast of LEN | 364 day |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: Tlast of LEN | 364 day |
Secondary
Primary Cohort: PK Parameter: Tlast of Teropavimab
Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Population: Participants in the Teropavimab PK Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: Tlast of Teropavimab | 364 day |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: Tlast of Teropavimab | 364 day |
Secondary
Primary Cohort: PK Parameter: Tlast of Zinlirvimab
Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Population: Participants in the Zinlirvimab PK Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: Tlast of Zinlirvimab | 364 day |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: Tlast of Zinlirvimab | 364 day |
Secondary
Primary Cohort: PK Parameter: Tmax of Teropavimab
Tmax is defined as the time (observed time point) of Cmax.
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Population: Participants in the Teropavimab PK Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: Tmax of Teropavimab | 1.16 hours |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: Tmax of Teropavimab | 2.24 hours |
Secondary
Primary Cohort: PK Parameter: Tmax of Zinlirvimab
Tmax is defined as the time (observed time point) of Cmax.
Time frame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Population: Participants in the Zinlirvimab PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 10 mg/kg | Primary Cohort: PK Parameter: Tmax of Zinlirvimab | 1.10 hours |
| Primary Cohort: LEN+Teropavimab+Zinlirvimab 30 mg/kg | Primary Cohort: PK Parameter: Tmax of Zinlirvimab | 1.00 hours |