NCT04648046

CAR-T Cells for HIV Infection

Safety and Anti-HIV Activity of Autologous CD4+ and CD8+ T Cells Transduced With a Lentiviral Vector Encoding Bi-specific Anti-gp120 CAR Molecules (LVgp120duoCAR-T) in Anti-retroviral Drug-treated HIV-1 Infection

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Steven Deeks · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Detailed description

A limited-center, open-label dose escalating phase I/IIa study of autologous T cells expressing LVgp120duoCAR molecules will be performed. Participants will be enrolled sequentially in up to three cohorts following 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. Following a 3+3 design, each cohort will enroll at least 3 participants. If there are no safety issues with dosing in a cohort, the investigators will proceed to the following cohort. If one participant in a cohort experiences a safety issue, an additional 3 individuals will be enrolled in that cohort to assess safety prior to proceeding to the next cohort. See below for Dose Escalation Procedures. The first 3 participants start at Cohort 1. Data from Cohort 1 will be submitted for FDA review prior to dosing Cohorts 2 and 3 to determine if cyclophosphamide conditioning is needed. Cohort 1: Participants will NOT undergo non-ablative conditioning with cyclophosphamide. A single dose of 3 x 105 cells/kg LVgp120duoCAR-T cells will be infused. ART will be interrupted immediately after infusion. Cohort 2: Participants will undergo non-ablative conditioning with cyclophosphamide. A single dose of 3 x 105 cells/kg LVgp120duoCAR-T cells will be infused. ART will be interrupted immediately after infusion. Cohort 3: Participants will undergo non-ablative conditioning with cyclophosphamide. A single dose of 1 x 106 cells/kg LVgp120duoCAR-T cells will be infused into the participant. ART will be interrupted immediately after infusion. Dose Escalation Procedures: 1. If, after 45 days of study treatment, no participant out of the initial 3 in a cohort exhibits a study treatment-related DLT, then the next cohort of participants will be treated at the subsequent cohort. 2. If, after 45 days of study treatment, 1 participant out of the initial 3 in a cohort exhibits a study treatment-related DLT, then up to 3 additional participants will be added at that dose level. 3. If no additional participant develops a study treatment-related DLT (i.e., 1/6 participants with DLT at that dose level), then the next cohort of participants will be treated at the next higher dose level. 4. However, if a second participant develops a study treatment-related DLT, even if it is before there are 6 total participants on that level, then the maximum tolerated dose (MTD) has been exceeded and no additional participants should be added to this or any higher doses. A total of 6 participants should then be treated on the next lowest dose level to ensure its tolerability and to better define the MTD. Thus, the MTD is defined as the highest assigned dose level at which \< 2/6 participants have a DLT. 5. If 2 participants in Cohort 1 experience a related DLT, the MTD will have been exceeded and no additional participants will be added at any higher level. 6. If the investigators experience DLTs in Cohort 1, the investigators will de-escalate the dose to 1 x 10\^5 cells per kg. If the investigators experience DLTs at the de-escalated dose of 1 x 10\^5 cells per kg, the study will stop.

Conditions

• HIV Infections

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Non-ablative conditioning with cyclophosphamide.
BIOLOGICAL	LVgp120duoCAR-T cells, low dose	A single dose of 3 x 10\^5 cells/kg LVgp120duoCAR-T cells will be infused.
BIOLOGICAL	LVgp120duoCAR-T cells, high dose	A single dose of 1 x 10\^6 cells/kg LVgp120duoCAR-T cells will be infused.
OTHER	Analytic Treatment Interruption	HIV antiretroviral therapy medications will be paused.

Timeline

• Start date: 2021-03-01
• Primary completion: 2028-12-31
• Completion: 2029-12-31
• First posted: 2020-12-01
• Last updated: 2026-04-09

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study