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

• ClinicalTrials.gov Identifier: NCT05281510
• Recruitment Status: Recruiting
• First Posted: March 16, 2022
• Last Update Posted: March 22, 2023
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

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).

Condition or disease	Intervention/treatment	Phase
HIV-1-infection	Drug: Vesatolimod; Biological: VRC07523LS; Biological: CAP256V2LS	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 9, 2022
• Estimated Primary Completion Date: November 2024
• Estimated Study Completion Date: November 2024

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 Name: GS-9620; Biological: VRC07523LS; Administered intravenously; Biological: CAP256V2LS; Administered intravenously

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [ Time Frame: First dose date up to 60 weeks ]
2. Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities [ Time Frame: First dose date up to 60 weeks ]

Secondary Outcome Measures :

1. Time to Viral Rebound (confirmed ≥ 50 copies/mL and ≥ 200 copies/mL) Following Analytical Treatment Interruption (ATI) [ Time Frame: Up to 60 weeks ]
2. The Change in Plasma Viral Load Set-point Following ATI [ Time Frame: Pre-antiretroviral therapy (ART) (Screening) and prior to ART reinitiation following ATI (maximum of 60 weeks) ]
3. Viral Load at the End of ATI [ Time Frame: Up to 60 weeks ]
4. Time to Antiretroviral Therapy (ART) Resumption Following ATI [ Time Frame: Up to 60 weeks ]
5. Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod (VES) [ Time Frame: Predose up to 48 hours postdose ]
   Cmax is defined as maximum observed concentration of drug.
6. PK Parameter: Tmax of VES [ Time Frame: Predose up to 48 hours postdose ]
   Tmax is defined as time (observed time point) of Cmax.
7. PK Parameter: Clast of VES [ Time Frame: Predose up to 48 hours postdose ]
   Clast is defined as last observed quantifiable concentration of the drug.
8. PK Parameter: Tlast of VES [ Time Frame: Predose up to 48 hours postdose ]
   Tlast is defined as time (observed time point) of Clast.
9. PK Parameter: AUCinf of VES [ Time Frame: 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).
10. PK Parameter: AUClast of VES [ Time Frame: 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.
11. PK Parameter: AUCexp of VES [ Time Frame: Predose up to 48 hours postdose ]
    AUCexp is defined as AUC extrapolated between AUClast and AUCinf.
12. PK Parameter: t1/2 of VES [ Time Frame: 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).
13. PK Parameter: CL/F of VES [ Time Frame: Predose up to 48 hours postdose ]
    CL/F is defined as clearance following extravascular administration.
14. PK Parameter: Vz/F of VES [ Time Frame: Predose up to 48 hours postdose ]
    Vz/F is defined as apparent volume of distribution.
15. PK Parameter: Cmax of VRC07-523LS and CAP256V2LS [ Time Frame: Predose up to Day 413 ]
    Cmax is defined as maximum observed concentration of drug.
16. PK Parameter: Tmax of VRC07-523LS and CAP256V2LS [ Time Frame: Predose up to Day 413 ]
    Tmax is defined as time (observed time point) of Cmax.
17. PK Parameter: Clast of VRC07-523LS and CAP256V2LS [ Time Frame: Predose up to Day 413 ]
    Clast is defined as last observed quantifiable concentration of the drug.
18. PK Parameter: Tlast of VRC07-523LS and CAP256V2LS [ Time Frame: Predose up to Day 413 ]
    Tlast is defined as time (observed time point) of Clast.
19. PK Parameter: AUCinf of VRC07-523LS and CAP256V2LS [ Time Frame: 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).
20. PK Parameter: AUClast of VRC07-523LS and CAP256V2LS [ Time Frame: Predose up to Day 413 ]
    AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.
21. PK Parameter: AUCexp of VRC07-523LS and CAP256V2LS [ Time Frame: Predose up to Day 413 ]
    AUCexp is defined as AUC extrapolated between AUClast and AUCinf.
22. PK Parameter: t1/2 of VRC07-523LS and CAP256V2LS [ Time Frame: 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).
23. PK Parameter: CL of VRC07-523LS and CAP256V2LS [ Time Frame: Predose up to Day 413 ]
    CL is defined as clearance following intravenous administration.
24. PK Parameter: Vss of VRC07-523LS and CAP256V2LS [ Time Frame: Predose up to Day 413 ]
    Vss is defined as the apparent volume of distribution at steady-state.
25. PK Parameter: Vz of VRC07-523LS and CAP256V2LS [ Time Frame: Predose up to Day 413 ]
    Vz is defined as volume of distribution of the drug after intravenous administration.
26. Percentage of Participants With Positive Anti-VRC07-523LS Antibodies [ Time Frame: Prebaseline (Day -13) up to Day 413 ]
27. Percentage of Participants With Positive Anti-CAP256V2LS Antibodies [ Time Frame: Prebaseline (Day -13) up to Day 413 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Gilead Clinical Study Information Center; 1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

Locations

South Africa

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

Umlazi, South Africa, 4066

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

More Information

Additional Information:

Gilead Clinical Trials Website 

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT05281510
• Other Study ID Numbers: GS-US-382-5445; DOH-27-082021-8379 ( Other Identifier: South African National Clinical Trials Registry )
• First Posted: March 16, 2022
• Last Update Posted: March 22, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Vesatolimod; Antiviral Agents; Anti-Infective Agents