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

Gilead Sciences20 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV-1-infection

Interventions

VesatolimodDRUG

Administered orally

VRC07523LSBIOLOGICAL

Administered intravenously

CAP256V2LSBIOLOGICAL

Administered intravenously

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (1)

FRESH Clinical Research Site: Females Rising through Education, Support and Health

Umlazi, South Africa

Outcomes

Primary Outcomes

Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

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.

Time frame: Up to 61.1 weeks

Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities

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.

Time frame: Up to 61.1 weeks

Secondary Outcomes

Time to Viral Rebound (Confirmed ≥ 50 Copies/mL and ≥ 200 Copies/mL) Following ATI

Virologic rebound is defined as at any visit a rebound in HIV-1 RNA to ≥ 50 copies/mL or ≥ 200 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled visit. Time to rebound (in weeks) = (date of rebound or censoring date - ATI start date + 1) / 7.

Time frame: Up to 56 weeks

Change in Plasma Viral Load Set-point Following ATI

Data from ClinicalTrials.gov

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Change in plasma viral load set-point between pre-ART value and prior to ART reinitiation following ATI was summarized. The pre-ART set point value is the HIV-RNA load count prior to start of initial ARV treatment recorded in the clinical database.

Time frame: 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

Baseline value was the last available value collected on or prior to first dose of study drug.

Time frame: Up to 48 weeks

Time to ART Resumption Following ATI

Time to ART resumption (in weeks) = (date of restart ART after ATI period start or censoring date - ATI start date + 1) / 7.

Time frame: Up to 56 weeks

Pharmacokinetic (PK) Parameter of VES: Cmax

Cmax is defined as maximum observed concentration of drug.