CD4 CAR+ ZFN-modified T Cells in HIV Therapy

NCT03617198 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 831464
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is being carried out to study a new way to possibly treat HIV. As part of this study, doctors will take some of your own white blood cells, called T-cells, and modify them so that they can identify and target your HIV cells. The purpose of the study is to evaluate the safety of these modified T cells and determine whether they have any effect on HIV infection.

Conditions

Hiv

Outcome Measures

Primary Outcomes (1)

• Number of subjects with treatment related adverse events.

  After subjects have received infusion and up to 5 years from Day 0 infusion.

Secondary Outcomes (7)

• Compare the percentage of enriched modified CD4 CAR+ CCR5 ZFN cells and their subsets.

  2 weeks post infusion, prior to prior to analytical treatment interruption (ATI), 6-9 months post infusion.

• Compare the change in CD4 count.

  Baseline, week 2 post infusion, prior to ATI, weeks 8, 12, 16 of ATI.

• Compare viral set point log 10 HIV RNA level.

  Baseline and 6-9 months post infusion

• Percentage of cells producing cytokines in response to HIV antigen/peptide as assessed by flow cytometry

  Baseline and 6-9 months post infusion

• Size of latent HIV reservoir as assessed by quantification of integrated copies of replication competent HIV

  Baseline, pre-treatment interruption, prior to ART reinitiation, 6-9 months post infusion, and end of primary follow up (8-12 months)

Study Arms (2)

Cohort 1

EXPERIMENTAL

Cohort 1 subjects will begin treatment interruption approximately 24 hours after they receive the modified T-cells. All other study procedures are the same as Cohort 2.

Biological: CD4 CAR+CCR5 ZFN T-cells

Cohort 2

EXPERIMENTAL

Cohort 2 subjects will begin treatment interruption approximately 8 weeks after they receive the modified T-cells. All other study procedures are the same as Cohort 1.

Biological: CD4 CAR+CCR5 ZFN T-cells

Interventions

CD4 CAR+CCR5 ZFN T-cells BIOLOGICAL

A dual cohort, open-label, randomized study of the safety and tolerability of a single infusion of autologous T cells genetically modified to express a CD4 chimeric antigen receptor while also having zinc finger nuclease-mediated disruption of the CCR5 gene

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• HIV-1 infection
• Clinically stable on first or second HAART regimen
• Screening CD4+ T cell count of ≥450 cells/mm3 within 30 days of enrollment; and a documented CD4 nadir of not lower than 200 cells/mm3
• Screening HIV-1 RNA that is ≤50 copies/mL within 30 days prior to enrollment
• HIV-1 RNA ≤50 copies/mL for at least 24 weeks prior to enrollment
• Adequate venous access and no other contraindications for leukapheresis
• Laboratory values within certain parameters, obtained within 30 days prior to enrollment
• Willing to comply with study-mandated evaluations
• Male or female, 18 years of age or older
• Ability and willingness to provide informed consent
• Karnofsky Performance Score of 70 or higher
• Negative HBsAg (hepatitis B) within 6 months prior to enrollment
• Negative HCV (hepatitis C) serology, or if positive, negative HCV RNA within 6 months prior to enrollment
• Have a recorded viral load set point prior to starting antiretroviral therapy

You may not qualify if:

• Acute or chronic hepatitis B or hepatitis C infection
• Current or prior AIDS diagnosis
• History of cancer or malignancy, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin
• History or any features on physical examination indicative of active or unstable cardiac disease or hemodynamic instability (subjects with a history of cardiac disease may participate with a physician's approval)
• History or any features of physical examination indicative of bleeding diathesis
• Have been previously treated with any HIV experimental vaccine within 6 months prior to screening, or any previous gene therapy using an integrating vector (subjects treated with placebo in an HIV vaccine study will not be excluded if documentation that they received placebo is provided)
• Breast-feeding, pregnant, or unwilling to use acceptable methods of birth control
• Anticipated use of aspirin, dipyridamole, warfarin, or any other medication that is likely to affect platelet function or other aspects of blood coagulation during the 2 week period prior to leukapheresis
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
• Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to the study screening visit
• Receipt of vaccination within 30 days prior to study screening visit
• Have an allergy to hypersensitivity to study product components (human serum albumin, DMSO and Dextran 40)
• Currently taking a non-nucleoside reverse transcriptase inhibitor (NNRTI)

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

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

Study Officials

• Pablo Tebas, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 9, 2018
• First Posted: August 6, 2018
• Study Start: July 31, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)