A Phase 1b Randomized, Blinded, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Broadly Neutralizing Antibodies (bNAbs) GS-5423 and GS-2872 in Combination With Capsid Inhibitor Lenacapavir (GS-6207) in Virologically Suppressed Adults With HIV-1 Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 23
- 主要终点
- Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Clinical pharmacologist and sponsor are not masked to treatment assignment.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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/Exclusion criteria may apply.
研究组 & 干预措施
Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg
Participants will receive a loading dose of 600 milligrams (mg) LEN orally on Day 1 and Day 2, along with 927 mg LEN as subcutaneous (SC) injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an intravenous (IV) infusion on Day 1.
干预措施: Oral Lenacapavir (Drug)
Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg
Participants will receive a loading dose of 600 milligrams (mg) LEN orally on Day 1 and Day 2, along with 927 mg LEN as subcutaneous (SC) injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an intravenous (IV) infusion on Day 1.
干预措施: Subcutaneous Lenacapavir (Drug)
Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg
Participants will receive a loading dose of 600 milligrams (mg) LEN orally on Day 1 and Day 2, along with 927 mg LEN as subcutaneous (SC) injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an intravenous (IV) infusion on Day 1.
干预措施: Teropavimab (Drug)
Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg
Participants will receive a loading dose of 600 milligrams (mg) LEN orally on Day 1 and Day 2, along with 927 mg LEN as subcutaneous (SC) injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an intravenous (IV) infusion on Day 1.
干预措施: Zinlirvimab (Drug)
Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg
Participants will receive 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 will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.
干预措施: Oral Lenacapavir (Drug)
Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg
Participants will receive 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 will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.
干预措施: Subcutaneous Lenacapavir (Drug)
Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg
Participants will receive 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 will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.
干预措施: Teropavimab (Drug)
Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg
Participants will receive 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 will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.
干预措施: Zinlirvimab (Drug)
Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg
Participants will receive 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 will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1.
干预措施: Oral Lenacapavir (Drug)
Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg
Participants will receive 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 will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1.
干预措施: Subcutaneous Lenacapavir (Drug)
Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg
Participants will receive 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 will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1.
干预措施: Teropavimab (Drug)
Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg
Participants will receive 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 will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1.
干预措施: Zinlirvimab (Drug)
Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg
Participants will receive 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 will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.
干预措施: Oral Lenacapavir (Drug)
Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg
Participants will receive 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 will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.
干预措施: Subcutaneous Lenacapavir (Drug)
Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg
Participants will receive 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 will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.
干预措施: Teropavimab (Drug)
Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg
Participants will receive 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 will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.
干预措施: Zinlirvimab (Drug)
结局指标
主要结局
Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)
时间窗: 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).
次要结局
- 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)
- 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)
- Primary Cohort: Percentage of Participants With Positive Anti-Teropavimab Antibodies(Week 26)
- Primary Cohort: Percentage of Participants With Positive Anti-zinlirvimab Antibodies(Week 26)
- 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)
- Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)(Day 1 up to Week 26)
- 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)
- 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)
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- Primary Cohort: PK Parameter: C26week of LEN(Week 26)
- Primary Cohort: PK Parameter: C26week of Teropavimab(Week 26)
- Primary Cohort: PK Parameter: C26week of Zinlirvimab(Week 26)