CAR-T Cells for HIV Infection

NCT04648046 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20-31976
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This is a limited-center, open-label dose escalating phase I/IIa study of autologous T cells expressing LVgp120duoCAR molecules in people with HIV infection. It will follow a 3+3 design. Dose escalation decisions will be made when a minimum of three participants have completed the safety-evaluation period (45 days) at a given dose level. Cohort 1 will undergo infusion of a single low-dose regimen of LVgp120duoCAR-T cells. Cohort 2 will undergo non-ablative conditioning with cyclophosphamide, followed by infusion of a single low-dose regimen of LVgp120duoCAR-T cells. Cohort 3 will undergo non-ablative conditioning with cyclophosphamide, followed infusion of a single high-dose regimen of LVgp120duoCAR-T cells. Following administration of the experimental therapy, HIV medications will be paused for participants in each group during an analytic treatment interruption.

Conditions

HIV Infections

Keywords

HIV; HIV/AIDS; CAR-T cells; HIV cure; HIV reservoir; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Number of participants reporting a new Grade 3 or greater adverse event that is definitely, probably, or possibly related to study treatment within 1 year of product administration.

  The primary safety outcome will be the number of participants reporting a new Grade 3 or greater adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, including signs/symptoms, lab toxicity or clinical event, that is definitely, probably, or possibly related to study treatment within 1 year of product administration.

  Within 1 year of product administration

• Number of participants achieving post-treatment control within 36 weeks of product administration.

  The primary efficacy outcome will be the proportion of individuals who achieve study-defined post-treatment control. The investigators will define post-treatment control in two ways. First, participants who fail to show any consistent rebound above 400 copies RNA/mL between Weeks 12 and Week 36 will be considered as having achieved post-treatment control. Second, participants who exhibit a rebound and eventually achieve 24 weeks of virus control will be considered as having achieved post-treatment control.

  Week 36

Secondary Outcomes (3)

• Persistence of LVgp120duoCAR-T cells in blood during therapy

  Week 12 through Week 36

• Persistence of LVgp120duoCAR-T cells in tissues during therapy

  Week 12 through Week 36

• Change in quantitative virologic measures of the HIV reservoir pre- and post-therapy

  Baseline and 36 weeks

Study Arms (3)

Low Dose CAR-T Cells Only

EXPERIMENTAL

Participants will NOT undergo non-ablative conditioning with cyclophosphamide. A single dose of 3 x 10\^5 cells/kg LVgp120duoCAR-T cells will be infused. ART will be interrupted immediately after infusion.

Biological: LVgp120duoCAR-T cells, low dose; Other: Analytic Treatment Interruption

Conditioning + Low Dose CAR-T Cells

EXPERIMENTAL

Participants will undergo non-ablative conditioning with cyclophosphamide. A single dose of 3 x 10\^5 cells/kg LVgp120duoCAR-T cells will be infused. ART will be interrupted immediately after infusion.

Drug: Cyclophosphamide; Biological: LVgp120duoCAR-T cells, low dose; Other: Analytic Treatment Interruption

Conditioning + High Dose CAR-T Cells

EXPERIMENTAL

Participants will undergo non-ablative conditioning with cyclophosphamide. A single dose of 1 x 10\^6 cells/kg LVgp120duoCAR-T cells will be infused into the participant. ART will be interrupted immediately after infusion.

Drug: Cyclophosphamide; Biological: LVgp120duoCAR-T cells, high dose; Other: Analytic Treatment Interruption

Interventions

Cyclophosphamide DRUG

Non-ablative conditioning with cyclophosphamide.

Conditioning + High Dose CAR-T Cells; Conditioning + Low Dose CAR-T Cells

LVgp120duoCAR-T cells, low dose BIOLOGICAL

A single dose of 3 x 10\^5 cells/kg LVgp120duoCAR-T cells will be infused.

Conditioning + Low Dose CAR-T Cells; Low Dose CAR-T Cells Only

LVgp120duoCAR-T cells, high dose BIOLOGICAL

A single dose of 1 x 10\^6 cells/kg LVgp120duoCAR-T cells will be infused.

Conditioning + High Dose CAR-T Cells

Analytic Treatment Interruption OTHER

HIV antiretroviral therapy medications will be paused.

Conditioning + High Dose CAR-T Cells; Conditioning + Low Dose CAR-T Cells; Low Dose CAR-T Cells Only

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age ≥ 18 and ≤ 65 years
• HIV-1 infection
• On continuous antiretroviral therapy for at least 12 months without any interruptions of greater than 14 consecutive days, and on a stable regimen that does not include a non-nucleoside reverse transcriptase inhibitor (NNRTI) for at least 4 weeks or any long-acting ART drug that may be active in the participant after ART interruption for up to one year, without plans to modify ART during the study period
• Screening plasma HIV RNA levels below the limit of quantification on all available determinations in past 12 months (isolated single values ≥ 40 but \< 200 copies/mL will be allowed if they were preceded and followed by undetectable viral load determinations)
• CD4+ T cell count nadir \> 300 cells/mm3
• Screening CD4+ T-cell count ≥ 500 cells/mm3
• Available ART treatment history and the capacity to construct an effective antiretroviral treatment regimen
• Willing to pause ART as part of the study

You may not qualify if:

• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
• ART regimen that includes a long-acting anti-HIV drug and/or NNRTI that may be active in the participant for up to one year after ART interruption
• ART regimen that includes protease inhibitor(s) and/or AZT. These drugs may increase the toxicity of cyclophosphamide.
• Any history of an HIV-associated malignancy, including Kaposi's sarcoma and any type of lymphoma, or virus-associated cancers
• History of or current active hepatitis B (HBV) infection defined as positive HBV surface antigen test. A positive anti-HBc regardless of HBsAg status.
• Active hepatitis C (HCV) infection
• Active or latent tuberculosis infection
• Chronic liver disease
• Active and poorly controlled atherosclerotic cardiovascular disease
• Unwillingness to abstain from sex or use barrier protection for any sexual activity during the treatment interruption.

Sponsors & Collaborators

• Steven Deeks: lead
• Caring Cross: collaborator

Study Sites (2)

University of California, Davis

Sacramento, California, 95817, United States

RECRUITING

Zuckerberg San Francisco General

San Francisco, California, 94110, United States

RECRUITING

Related Publications (1)

• Anthony-Gonda K, Ray A, Su H, Wang Y, Xiong Y, Lee D, Block A, Chilunda V, Weiselberg J, Zemelko L, Wang YY, Kleinsorge-Block S, Reese JS, de Lima M, Ochsenbauer C, Kappes JC, Dimitrov DS, Orentas R, Deeks SG, Rutishauser RL, Berman JW, Goldstein H, Dropulic B. In vivo killing of primary HIV-infected cells by peripheral-injected early memory-enriched anti-HIV duoCAR T cells. JCI Insight. 2022 Nov 8;7(21):e161698. doi: 10.1172/jci.insight.161698.

  PMID: 36345941 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Steven Deeks, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca Hoh

CONTACT

415-476-4082; rebecca.hoh@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: The clinical trial is an open-label dose escalating phase I/IIa study of autologous T cells expressing LVgp120duoCAR molecules that target and kill HIV-1 gp120 expressing cells. Participants will be enrolled sequentially in up to three sequentially enrolled cohorts in a 3+3 design. Dose escalation decisions will be made when a minimum of three participants have completed the safety-evaluation period (45 days) at a given dose level. No dose escalation will be allowed in an individual participant, and participants who have dose limiting adverse events will reinstate ART therapy at first available opportunity. There are 3 dose escalation cohorts with the first 3 participants starting at Cohort 1.

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: December 1, 2020
• Study Start: March 1, 2021
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)