Study of VRC07-523LS, CAP256V2LS, and Vesatolimod, in Early Antiretroviral-treated HIV-1 Clade C-infected Women
- Conditions
- HIV-1-infection
- Interventions
- Registration Number
- NCT05281510
- Lead Sponsor
- Gilead Sciences
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 20
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Age ≥ 18 years
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Females recruited from the Females Rising through Education, Support, and Health (FRESH) acute human immunodeficiency virus (HIV) infection cohort.
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Plasma human immunodeficiency -1 (HIV-1) ribonucleic acid (RNA) levels < 50 copies/mL at the screening visit.
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On antiretroviral (ART) regimen for ≥ 12 consecutive months prior to the screening visit.
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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
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Women of childbearing potential to have documentation of agreement to follow study contraceptive requirements.
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Documented plasma HIV-1 RNA < 50 copies/mL for 12 consecutive months prior to the screening visit.
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In the judgment of the investigator, be in good general health.
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Documented history of viral sensitivity to VRC07-523LS or CAP256V2LS at the screening visit.
Key
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Have poor venous access that limits phlebotomy.
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Positive serum pregnancy test.
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Nursing participants.
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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
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Have current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance or individual's safety.
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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.
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Have previous or current receipt of humanized or human monoclonal antibody (mAbs), or polyclonal immunoglobulin.
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Have previous history of an antidrug antibodies response to a therapeutic agent.
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Have previous receipt of an HIV vaccine.
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Received any vaccine or immunomodulatory medication within 4 weeks prior to screening.
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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
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Have current Class C acquired immunodeficiency syndrome (AIDS)-defining condition.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description VRC07523LS + CAP256V2LS + Vesatolimod (VES) CAP256V2LS Participants will receive VES 6 mg (or up to 8 mg) every 2 weeks, for a total of 10 doses + VRC07-523LS and CAP256V2LS 20 mg/kg each on Day 7. VRC07523LS + CAP256V2LS + Vesatolimod (VES) VRC07523LS Participants will receive VES 6 mg (or up to 8 mg) every 2 weeks, for a total of 10 doses + VRC07-523LS and CAP256V2LS 20 mg/kg each on Day 7. VRC07523LS + CAP256V2LS + Vesatolimod (VES) Vesatolimod Participants will receive VES 6 mg (or up to 8 mg) every 2 weeks, for a total of 10 doses + VRC07-523LS and CAP256V2LS 20 mg/kg each on Day 7.
- Primary Outcome Measures
Name Time Method Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities First dose date up to 60 weeks Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) First dose date up to 60 weeks
- Secondary Outcome Measures
Name Time Method PK Parameter: Clast of VES Predose up to 48 hours postdose Clast is defined as last observed quantifiable concentration of the drug.
PK Parameter: Clast of VRC07-523LS and CAP256V2LS Predose up to Day 413 Clast is defined as last observed quantifiable concentration of the drug.
PK Parameter: AUClast of VRC07-523LS and CAP256V2LS Predose up to Day 413 AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.
Viral Load at the End of ATI Up to 60 weeks PK Parameter: AUCinf of VES Predose up to 48 hours postdose AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz).
Time to Viral Rebound (confirmed ≥ 50 copies/mL and ≥ 200 copies/mL) Following Analytical Treatment Interruption (ATI) Up to 60 weeks The Change in Plasma Viral Load Set-point Following ATI Pre-antiretroviral therapy (ART) (Screening) and prior to ART reinitiation following ATI (maximum of 60 weeks) PK Parameter: Tlast of VES Predose up to 48 hours postdose Tlast is defined as time (observed time point) of Clast.
PK Parameter: Vss of VRC07-523LS and CAP256V2LS Predose up to Day 413 Vss is defined as the apparent volume of distribution at steady-state.
PK Parameter: Vz of VRC07-523LS and CAP256V2LS Predose up to Day 413 Vz is defined as volume of distribution of the drug after intravenous administration.
Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod (VES) Predose up to 48 hours postdose Cmax is defined as maximum observed concentration of drug.
PK Parameter: AUCinf of VRC07-523LS and CAP256V2LS Predose up to Day 413 AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz).
Time to Antiretroviral Therapy (ART) Resumption Following ATI Up to 60 weeks PK Parameter: Tmax of VES Predose up to 48 hours postdose Tmax is defined as time (observed time point) of Cmax.
PK Parameter: AUClast of VES Predose up to 48 hours postdose AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.
PK Parameter: AUCexp of VES Predose up to 48 hours postdose AUCexp is defined as AUC extrapolated between AUClast and AUCinf.
PK Parameter: t1/2 of VES Predose up to 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: Vz/F of VES Predose up to 48 hours postdose Vz/F is defined as apparent volume of distribution.
PK Parameter: AUCexp of VRC07-523LS and CAP256V2LS Predose up to Day 413 AUCexp is defined as AUC extrapolated between AUClast and AUCinf.
PK Parameter: CL/F of VES Predose up to 48 hours postdose CL/F is defined as clearance following extravascular administration.
PK Parameter: Cmax of VRC07-523LS and CAP256V2LS Predose up to Day 413 Cmax is defined as maximum observed concentration of drug.
PK Parameter: Tmax of VRC07-523LS and CAP256V2LS Predose up to Day 413 Tmax is defined as time (observed time point) of Cmax.
PK Parameter: Tlast of VRC07-523LS and CAP256V2LS Predose up to Day 413 Tlast is defined as time (observed time point) of Clast.
PK Parameter: CL of VRC07-523LS and CAP256V2LS Predose up to Day 413 CL is defined as clearance following intravenous administration.
Percentage of Participants With Positive Anti-CAP256V2LS Antibodies Prebaseline (Day -13) up to Day 413 PK Parameter: t1/2 of VRC07-523LS and CAP256V2LS Predose up to Day 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).
Percentage of Participants With Positive Anti-VRC07-523LS Antibodies Prebaseline (Day -13) up to Day 413
Trial Locations
- Locations (1)
FRESH Clinical Research Site: Females Rising through Education, Support and Health
🇿🇦Umlazi, South Africa