A Phase 2a Study to Evaluate the Safety and Tolerability of a Regimen of Dual Anti-HIV Envelope Antibodies, VRC07-523LS and CAP256V2LS, in a Sequential Regimen With a TLR7 Agonist, Vesatolimod, in Early Antiretroviral-Treated HIV-1 Clade C-Infected Women
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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/Exclusion criteria may apply.
研究组 & 干预措施
VRC07523LS + CAP256V2LS + Vesatolimod (VES)
In Period 1 (Days 0-28), participants will receive ART through Period. On Days 0 & 14, participants will be administered VES 6mg orally and on Day 28, participants will be administered VES either 6 or 8mg orally. VRC07-523LS & CAP256V2LS 20mg/kg will be administered intravenously on Day 7. In Period 2 (Days 29-133 or until ART restart), participants will discontinue ART at Day 35 and remain off ART until reaching ART restart criteria. Participants will receive VES 6 or 8mg orally every 2 weeks from Day 29 or until plasma HIV-1 RNA is >=5000 copies/mL. In Period 3, (Days 134-336 or until ART restart), participants will continue ATI and no study treatment will be administered. In Period 4, (Days 337-413) participants who have not met ART restart criteria by Day 337 may choose to restart ART (Period 4a) or may choose to continue ATI until end of study (Period 4B). Any participants who meet ART restart criteria before the end of the study will remain in follow-up on ART (Period 4A).
干预措施: Vesatolimod (Drug)
VRC07523LS + CAP256V2LS + Vesatolimod (VES)
In Period 1 (Days 0-28), participants will receive ART through Period. On Days 0 & 14, participants will be administered VES 6mg orally and on Day 28, participants will be administered VES either 6 or 8mg orally. VRC07-523LS & CAP256V2LS 20mg/kg will be administered intravenously on Day 7. In Period 2 (Days 29-133 or until ART restart), participants will discontinue ART at Day 35 and remain off ART until reaching ART restart criteria. Participants will receive VES 6 or 8mg orally every 2 weeks from Day 29 or until plasma HIV-1 RNA is >=5000 copies/mL. In Period 3, (Days 134-336 or until ART restart), participants will continue ATI and no study treatment will be administered. In Period 4, (Days 337-413) participants who have not met ART restart criteria by Day 337 may choose to restart ART (Period 4a) or may choose to continue ATI until end of study (Period 4B). Any participants who meet ART restart criteria before the end of the study will remain in follow-up on ART (Period 4A).
干预措施: VRC07523LS (Biological)
VRC07523LS + CAP256V2LS + Vesatolimod (VES)
In Period 1 (Days 0-28), participants will receive ART through Period. On Days 0 & 14, participants will be administered VES 6mg orally and on Day 28, participants will be administered VES either 6 or 8mg orally. VRC07-523LS & CAP256V2LS 20mg/kg will be administered intravenously on Day 7. In Period 2 (Days 29-133 or until ART restart), participants will discontinue ART at Day 35 and remain off ART until reaching ART restart criteria. Participants will receive VES 6 or 8mg orally every 2 weeks from Day 29 or until plasma HIV-1 RNA is >=5000 copies/mL. In Period 3, (Days 134-336 or until ART restart), participants will continue ATI and no study treatment will be administered. In Period 4, (Days 337-413) participants who have not met ART restart criteria by Day 337 may choose to restart ART (Period 4a) or may choose to continue ATI until end of study (Period 4B). Any participants who meet ART restart criteria before the end of the study will remain in follow-up on ART (Period 4A).
干预措施: CAP256V2LS (Biological)
结局指标
主要结局
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
时间窗: 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
时间窗: 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.
次要结局
- Time to Viral Rebound (Confirmed ≥ 50 Copies/mL and ≥ 200 Copies/mL) Following ATI(Up to 56 weeks)
- Change in Plasma Viral Load Set-point Following ATI(Pre-ART (Screening) and prior to ART reinitiation following ATI (Up to 56 weeks))
- Change From Baseline of Viral Load at the End of ATI(Up to 48 weeks)
- Time to ART Resumption Following ATI(Up to 56 weeks)
- Pharmacokinetic (PK) Parameter of VES: Cmax(Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose)
- PK Parameter of VES: Tmax(Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose)
- PK Parameter of VES: Clast(Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose)
- PK Parameter of VES: Tlast(Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose)
- PK Parameter of VES: AUCinf(Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose)
- PK Parameter of VES: AUClast(Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose)
- PK Parameter of VES: AUCexp(Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose)
- PK Parameter of VES: t1/2(Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose)
- PK Parameter of VES: CL/F(Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose)
- PK Parameter of VES: Vz/F(Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Percentage of Participants With Treatment-emergent Positive Anti-VRC07-523LS Antibodies(Prebaseline (Day -13) up to Day 413)
- 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)
- Percentage of Participants With Treatment-emergent Positive Anti-CAP256V2LS Antibodies(Prebaseline (Day -13) up to Day 413)