Study of VRC07-523LS, CAP256V2LS, and Vesatolimod, in Early Antiretroviral-treated HIV-1 Clade C-infected Women

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Vesatolimod
* Biological: VRC07523LS
* Biological: CAP256V2LS


Participation Criteria
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Eligibility Criteria
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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/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VRC07523LS + CAP256V2LS + Vesatolimod (VES)<br>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. | Drug: Vesatolimod<br>* Administered orally<br>* Other names: GS-9620;Biological: VRC07523LS<br>* Administered intravenously<br>Biological: CAP256V2LS<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) |  | First dose date up to 60 weeks | 
| Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities |  | First dose date up to 60 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| Viral Load at the End of ATI |  | Up to 60 weeks | 
| Time to Antiretroviral Therapy (ART) Resumption Following ATI |  | Up to 60 weeks | 
| Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod (VES) | Cmax is defined as maximum observed concentration of drug. | Predose up to 48 hours postdose | 
| PK Parameter: Tmax of VES | Tmax is defined as time (observed time point) of Cmax. | Predose up to 48 hours postdose | 
| PK Parameter: Clast of VES | Clast is defined as last observed quantifiable concentration of the drug. | Predose up to 48 hours postdose | 
| PK Parameter: Tlast of VES | Tlast is defined as time (observed time point) of Clast. | Predose up to 48 hours postdose | 
| PK Parameter: AUCinf of VES | AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz). | Predose up to 48 hours postdose | 
| PK Parameter: AUClast of VES | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. | Predose up to 48 hours postdose | 
| PK Parameter: AUCexp of VES | AUCexp is defined as AUC extrapolated between AUClast and AUCinf. | Predose up to 48 hours postdose | 
| PK Parameter: t1/2 of VES | 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). | Predose up to 48 hours postdose | 
| PK Parameter: CL/F of VES | CL/F is defined as clearance following extravascular administration. | Predose up to 48 hours postdose | 
| PK Parameter: Vz/F of VES | Vz/F is defined as apparent volume of distribution. | Predose up to 48 hours postdose | 
| PK Parameter: Cmax of VRC07-523LS and CAP256V2LS | Cmax is defined as maximum observed concentration of drug. | Predose up to Day 413 | 
| PK Parameter: Tmax of VRC07-523LS and CAP256V2LS | Tmax is defined as time (observed time point) of Cmax. | Predose up to Day 413 | 
| PK Parameter: Clast of VRC07-523LS and CAP256V2LS | Clast is defined as last observed quantifiable concentration of the drug. | Predose up to Day 413 | 
| PK Parameter: Tlast of VRC07-523LS and CAP256V2LS | Tlast is defined as time (observed time point) of Clast. | Predose up to Day 413 | 
| PK Parameter: AUCinf of VRC07-523LS and CAP256V2LS | AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz). | Predose up to Day 413 | 
| PK Parameter: AUClast of VRC07-523LS and CAP256V2LS | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. | Predose up to Day 413 | 
| PK Parameter: AUCexp of VRC07-523LS and CAP256V2LS | AUCexp is defined as AUC extrapolated between AUClast and AUCinf. | Predose up to Day 413 | 
| PK Parameter: t1/2 of VRC07-523LS and CAP256V2LS | 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). | Predose up to Day 413 | 
| PK Parameter: CL of VRC07-523LS and CAP256V2LS | CL is defined as clearance following intravenous administration. | Predose up to Day 413 | 
| PK Parameter: Vss of VRC07-523LS and CAP256V2LS | Vss is defined as the apparent volume of distribution at steady-state. | Predose up to Day 413 | 
| PK Parameter: Vz of VRC07-523LS and CAP256V2LS | Vz is defined as volume of distribution of the drug after intravenous administration. | Predose up to Day 413 | 
| Percentage of Participants With Positive Anti-VRC07-523LS Antibodies |  | Prebaseline (Day -13) up to Day 413 | 
| Percentage of Participants With Positive Anti-CAP256V2LS Antibodies |  | Prebaseline (Day -13) up to Day 413 |