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

HIV-1-infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05281510
• Other study ID #: GS-US-382-5445
• Secondary ID: DOH-27-082021-83
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 9, 2022
• Est. completion date: March 2025

Study information

• Verified date: January 2024
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• Vesatolimod
Administered orally

Biological:
• VRC07523LS
Administered intravenously
• CAP256V2LS
Administered intravenously

Locations

Country	Name	City	State
South Africa	FRESH Clinical Research Site: Females Rising through Education, Support and Health	Umlazi

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)		First dose date up to 60 weeks
Primary	Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities		First dose date up to 60 weeks
Secondary	Time to Viral Rebound (confirmed = 50 copies/mL and = 200 copies/mL) Following Analytical Treatment Interruption (ATI)		Up to 60 weeks
Secondary	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)
Secondary	Viral Load at the End of ATI		Up to 60 weeks
Secondary	Time to Antiretroviral Therapy (ART) Resumption Following ATI		Up to 60 weeks
Secondary	Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod (VES)	Cmax is defined as maximum observed concentration of drug.	Predose up to 48 hours postdose
Secondary	PK Parameter: Tmax of VES	Tmax is defined as time (observed time point) of Cmax.	Predose up to 48 hours postdose
Secondary	PK Parameter: Clast of VES	Clast is defined as last observed quantifiable concentration of the drug.	Predose up to 48 hours postdose
Secondary	PK Parameter: Tlast of VES	Tlast is defined as time (observed time point) of Clast.	Predose up to 48 hours postdose
Secondary	PK Parameter: AUCinf of VES	AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/?z).	Predose up to 48 hours postdose
Secondary	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
Secondary	PK Parameter: AUCexp of VES	AUCexp is defined as AUC extrapolated between AUClast and AUCinf.	Predose up to 48 hours postdose
Secondary	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 (?z).	Predose up to 48 hours postdose
Secondary	PK Parameter: CL/F of VES	CL/F is defined as clearance following extravascular administration.	Predose up to 48 hours postdose
Secondary	PK Parameter: Vz/F of VES	Vz/F is defined as apparent volume of distribution.	Predose up to 48 hours postdose
Secondary	PK Parameter: Cmax of VRC07-523LS and CAP256V2LS	Cmax is defined as maximum observed concentration of drug.	Predose up to Day 413
Secondary	PK Parameter: Tmax of VRC07-523LS and CAP256V2LS	Tmax is defined as time (observed time point) of Cmax.	Predose up to Day 413
Secondary	PK Parameter: Clast of VRC07-523LS and CAP256V2LS	Clast is defined as last observed quantifiable concentration of the drug.	Predose up to Day 413
Secondary	PK Parameter: Tlast of VRC07-523LS and CAP256V2LS	Tlast is defined as time (observed time point) of Clast.	Predose up to Day 413
Secondary	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/?z).	Predose up to Day 413
Secondary	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
Secondary	PK Parameter: AUCexp of VRC07-523LS and CAP256V2LS	AUCexp is defined as AUC extrapolated between AUClast and AUCinf.	Predose up to Day 413
Secondary	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 (?z).	Predose up to Day 413
Secondary	PK Parameter: CL of VRC07-523LS and CAP256V2LS	CL is defined as clearance following intravenous administration.	Predose up to Day 413
Secondary	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
Secondary	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
Secondary	Percentage of Participants With Positive Anti-VRC07-523LS Antibodies		Prebaseline (Day -13) up to Day 413
Secondary	Percentage of Participants With Positive Anti-CAP256V2LS Antibodies		Prebaseline (Day -13) up to Day 413

External Links

•   Gilead Clinical Trials Website