CMV-specific HIV-CAR T Cells as Immunotherapy for HIV/AIDS

NCT06252402 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 22508
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

Human immunodeficiency virus type 1 (HIV-1) causes a persistent infection that ultimately leads to acquired immunodeficiency syndrome (AIDS). Treatment of HIV-1 infection with combination anti-retroviral therapy (ART) suppresses HIV-1 replication to undetectable viral levels and saves lives. Nevertheless, ART cannot eradicate latent cellular reservoirs of the virus, and HIV-1 infection remains a life-long battle. Adoptive cellular immunotherapy using chimeric antigen receptor (CAR) engineered T cells directed against HIV-1 envelope subunit protein gp120 (HIVCAR T cells) may provide a safe and effective way to eliminate HIV-infected cells. However, the number of HIV-infected cells is low in participants under ART, and CAR T cells disappear if they are not stimulated by their target antigens. Interestingly, about 95% of HIV-1-infected individuals are CMV-seropositive and CMV-specific T cells have been shown to persist. To overcome the CAR T cells low persistence issue, we propose to make HIV-CAR T cells using autologous cytomegalovirus (CMV)-specific T cells, which can be stimulated by endogenous CMV in vivo. The overall hypothesis of this first-in-human Phase 1, open-label, single-arm study is that endogenous immune signals to CMV-specific T cells can maintain the presence of autologous bispecific CMV/HIV-CAR T cells in healthy people living with HIV-1 (PLWH), and achieve long-term remission in the presence of ART.

Conditions

HIV-1

Keywords

HIV-1, PLWH (Healthy People Living with HIV-1) autologus; CMV-specific T cells, anti-retroviral therapy (ART), Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicities (DLT)

  Toxicity will be graded per CTCAE v5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Criteria on CRS/Neurotoxicity: DLT.

  Up to 28 days after the infusion

• Toxicity profile

  Toxicity will be graded per CTCAE v5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Criteria on CRS/Neurotoxicity: all other toxicities to define the toxicity profile.

  Up to 28 days after the infusion

Secondary Outcomes (4)

• CD4+ T cell count and HIV RNA levels

  Up to 28 days after the infusion

• EGFR+ CD3+ T cells

  Up to 28 days after the infusion

• Cytokine levels

  Up to 28 days after the infusion

• Number of CMV/HIV-CAR T cells

  Up to 28 days after the infusion

Study Arms (3)

Dose Level -1

EXPERIMENTAL

EGFR+ T Cell Dose (Day 0) 5 x 10\^6 cells

Biological: CMV/HIV-CAR T Cells

Dose Level +1

EXPERIMENTAL

EGFR+ T Cell Dose (Day 0) 25 x 10\^6 cells

Biological: CMV/HIV-CAR T Cells

Dose Level +2

EXPERIMENTAL

EGFR+ T Cell Dose (Day 0) 50 x 10\^6 cells

Biological: CMV/HIV-CAR T Cells

Interventions

CMV/HIV-CAR T Cells BIOLOGICAL

Eligible participants will temporarily interrupt their ART regimen for 4 days prior to leukapheresis to prevent residual cell drug levels that could inhibit lentiviral transduction of the T cells during CAR T cewll manufacturing. Participants will resume their ART regimen immediately after leukapheresis. Once the final cell product is released, participants will receive a single intravenous (IV)infusion of autologous CMV/HIV-CAT T cells (defined as Day 0). Up to three doses of CMV/HIV-CAR T cewlls may be explored.

Dose Level +1; Dose Level +2; Dose Level -1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be ≥ 18 years of age at the time of screening;
• Karnofsky Performance Status (KPS) ≥ 70;
• Documented HIV-1 infection anytime prior to study entry.;
• On stable ART with undetectable HIV-1 RNA (i.e \< 20 copies /mL) for at least 48 weeks prior to screening (2 plasma HIV-1 RNA blips 25-200 copies/mL are allowable);
• CD4+ cell count ≥ 450 cells/μL;
• Adequate organ function;
• Willingness to interrupt ART regimen for 4 days prior to leukapheresis;
• Not pregnant or breastfeeding.

You may not qualify if:

• Concurrent illness or comorbid condition;
• History of resistance to two or more classes of antiretroviral drugs;
• History of prior receipt of an experimental HIV-1, immunotherapeutic agent, or gene therapy product.

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

UCSD, Division of Infectious Diseases and Global Public Health

San Diego, California, 92093, United States

RECRUITING

Study Officials

• John H. Baird, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

• David (Davey) Smith, MD

  UCSD, San Diego Center for AIDS Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marvin Hanashiro

CONTACT

(619) 543-3740; mhanashiro@health.ucsd.edu

Steven Hendrickx

CONTACT

(619) 543-6968; smhendrickx@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 9, 2024
• Study Start: December 19, 2024
• Primary Completion (Estimated): December 11, 2026
• Study Completion (Estimated): December 11, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)