Clinical trial NCT05281510: Study of VRC07-523LS, CAP256V2LS, and Vesatolimod, in Early Antiretroviral-treated HIV-1 Clade C-infected Women
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1-infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2022-03-16
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: First dose date up to 60 weeks
measure: Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities
timeFrame: First dose date up to 60 weeks
Secondary outcomes:
measure: Time to Viral Rebound (confirmed ≥ 50 copies/mL and ≥ 200 copies/mL) Following Analytical Treatment Interruption (ATI)
timeFrame: Up to 60 weeks
measure: The Change in Plasma Viral Load Set-point Following ATI
timeFrame: Pre-antiretroviral therapy (ART) (Screening) and prior to ART reinitiation following ATI (maximum of 60 weeks)
measure: Viral Load at the End of ATI
timeFrame: Up to 60 weeks
measure: Time to Antiretroviral Therapy (ART) Resumption Following ATI
timeFrame: Up to 60 weeks
measure: Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod (VES)
timeFrame: Predose up to 48 hours postdose
measure: PK Parameter: Tmax of VES
timeFrame: Predose up to 48 hours postdose
measure: PK Parameter: Clast of VES
timeFrame: Predose up to 48 hours postdose
measure: PK Parameter: Tlast of VES
timeFrame: Predose up to 48 hours postdose
measure: PK Parameter: AUCinf of VES
timeFrame: Predose up to 48 hours postdose
measure: PK Parameter: AUClast of VES
timeFrame: Predose up to 48 hours postdose
measure: PK Parameter: AUCexp of VES
timeFrame: Predose up to 48 hours postdose
measure: PK Parameter: t1/2 of VES
timeFrame: Predose up to 48 hours postdose
measure: PK Parameter: CL/F of VES
timeFrame: Predose up to 48 hours postdose
measure: PK Parameter: Vz/F of VES
timeFrame: Predose up to 48 hours postdose
measure: PK Parameter: Cmax of VRC07-523LS and CAP256V2LS
timeFrame: Predose up to Day 413
measure: PK Parameter: Tmax of VRC07-523LS and CAP256V2LS
timeFrame: Predose up to Day 413
measure: PK Parameter: Clast of VRC07-523LS and CAP256V2LS
timeFrame: Predose up to Day 413
measure: PK Parameter: Tlast of VRC07-523LS and CAP256V2LS
timeFrame: Predose up to Day 413
measure: PK Parameter: AUCinf of VRC07-523LS and CAP256V2LS
timeFrame: Predose up to Day 413
measure: PK Parameter: AUClast of VRC07-523LS and CAP256V2LS
timeFrame: Predose up to Day 413
measure: PK Parameter: AUCexp of VRC07-523LS and CAP256V2LS
timeFrame: Predose up to Day 413
measure: PK Parameter: t1/2 of VRC07-523LS and CAP256V2LS
timeFrame: Predose up to Day 413
measure: PK Parameter: CL of VRC07-523LS and CAP256V2LS
timeFrame: Predose up to Day 413
measure: PK Parameter: Vss of VRC07-523LS and CAP256V2LS
timeFrame: Predose up to Day 413
measure: PK Parameter: Vz of VRC07-523LS and CAP256V2LS
timeFrame: Predose up to Day 413
measure: Percentage of Participants With Positive Anti-VRC07-523LS Antibodies
timeFrame: Prebaseline (Day -13) up to Day 413
measure: Percentage of Participants With Positive Anti-CAP256V2LS Antibodies
timeFrame: Prebaseline (Day -13) up to Day 413
Other outcomes:
Locations:
city: Umlazi
country: South Africa
facility: FRESH Clinical Research Site: Females Rising through Education, Support and Health
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: