Study of VRC07-523LS, CAP256V2LS, and Vesatolimod, in Early Antiretroviral-treated HIV-1 Clade C-infected Women
Study Details
Study Description
Brief Summary
The primary objective of this study is to evaluate safety and tolerability of dual anti-human immunodeficiency virus (HIV) envelope monoclonal antibodies (mAbs), VRC07-523LS and CAP256V2LS, in a sequential regimen with a toll-like receptor (TLR)7 agonist, vesatolimod (VES), when administered in virologically suppressed HIV-1 Clade C-infected women on antiretroviral therapy (ART) and during analytical treatment interruption (ATI).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: VRC07523LS + CAP256V2LS + Vesatolimod (VES) 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
Administered orally
Other Names:
Biological: VRC07523LS
Administered intravenously
Biological: CAP256V2LS
Administered intravenously
|
Outcome Measures
Primary Outcome Measures
- 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
- 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) [Predose up to 48 hours postdose]
Cmax is defined as maximum observed concentration of drug.
- PK Parameter: Tmax of VES [Predose up to 48 hours postdose]
Tmax is defined as time (observed time point) of Cmax.
- PK Parameter: Clast of VES [Predose up to 48 hours postdose]
Clast is defined as last observed quantifiable concentration of the drug.
- PK Parameter: Tlast of VES [Predose up to 48 hours postdose]
Tlast is defined as time (observed time point) of Clast.
- 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).
- 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: CL/F of VES [Predose up to 48 hours postdose]
CL/F is defined as clearance following extravascular administration.
- PK Parameter: Vz/F of VES [Predose up to 48 hours postdose]
Vz/F is defined as apparent volume of distribution.
- 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: Clast of VRC07-523LS and CAP256V2LS [Predose up to Day 413]
Clast is defined as last observed quantifiable concentration of the drug.
- 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: 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).
- 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.
- 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: 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).
- PK Parameter: CL of VRC07-523LS and CAP256V2LS [Predose up to Day 413]
CL is defined as clearance following intravenous administration.
- 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.
- 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]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Females recruited from the Females Rising through Education, Support, and Health (FRESH) acute human immunodeficiency virus (HIV) infection cohort.
-
Plasma HIV-1 ribonucleic acid (RNA) levels < 50 copies/mL at the screening visit
-
Antiretroviral therapy (ART) initiated at detection of acute HIV-1 infection (Fiebig I-IV)
-
On 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 and CAP256V2LS at the screening visit
Key Exclusion Criteria:
-
Positive serum pregnancy test
-
Nursing females
-
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 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | FRESH Clinical Research Site: Females Rising through Education, Support and Health | Umlazi | South Africa | 4066 |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- GS-US-382-5445
- DOH-27-082021-8379