HIV-1 Specific T -Cells (HST-NEETs) for HIV-Infected Individuals

NCT03485963 | Completed Phase 1 FDA Drug

• 1 other identifier: Pro00009968
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase I, multi-site, study of the safety, immunologic and virologic responses of ex vivo expanded HIV-1 multi-antigen specific T-cell therapy (HST-NEET) as a therapeutic strategy in HIV-infected individuals suppressed on antiretroviral therapy (ART).

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• Incidence of Product-Emergent Adverse Events

  Occurrence of any ≥ Grade 3 AE including signs/symptoms, lab toxicities, and/or clinical events, that is possibly, probably or definitely related to study treatment any time from the first day of study treatment until 28 days after the last infusion. Safety data will include local and systemic signs and symptoms, laboratory measures of safety/toxicity, and all adverse and serious adverse events. Safety data will be routinely collected throughout the duration of the study. Relationship to study treatment will be judged by the protocol team. If any Grade 4 or 5 Serious Adverse Events occur, this will trigger an immediate pause in the protocol while the relationship to the T cell therapeutic is evaluated. If the attribution is deemed probably or definitely related to the study agent, the protocol will stop.

  from the first day of study treatment until 28 days after the last infusion.

Secondary Outcomes (1)

• HST-NEETS responses

  12 months

Study Arms (1)

Fixed dose HIV-1 specific T-cells (HST-NEETs)

EXPERIMENTAL

Patients will be screened for eligibility in Step 1 and undergo a blood draw of 100-120mL to allow production of autologous HST-NEETS. patients will receive a fixed dose of 2x10e7/m2. For the first 3 recipients, the infusions will occur 4 weeks apart. If no adverse reactions occur that are attributable to the HST-NEETs, the recipients thereafter will receive the two infusions separated by 2 weeks.

Biological: HST-NEETs

Interventions

HST-NEETs BIOLOGICAL

The primary objective of this study is to evaluate the safety and tolerability of expanded HIV-specific T cell therapy (HST-NEETs) in HIV-infected individuals suppressed on cART. Patients with a partial response or stable disease 8 weeks after T-cell infusion were eligible to receive additional T-cells, consisting of the same number of cells as their second injection.

Fixed dose HIV-1 specific T-cells (HST-NEETs)

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years and \< 65 years of age
• Confirmation of HIV-1 infection
• \- any licensed ELISA test kit which is confirmed by Western blot or Multispot HIV-1/HIV-2 assay prior to screening. HIV culture, HIV antigen, plasma HIV RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
• On potent antiretroviral therapy, defined as at least 2 nucleoside/nucleotide reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor, integrase inhibitor, or a protease inhibitor without interruption (Interruption is defined as missing doses by self report for no more than two (2) consecutive days or more than four (4) cumulative days) in the 12 weeks prior to cell procurement for HST NEETs manufacturing. Other potent fully suppressive antiretroviral combinations will be considered on a case- by-case basis. Prior changes in or elimination of medications for easier dosing schedule, intolerance, toxicity, or other reasons are permitted if an alternative suppressive regimen was maintained under the compliance criteria above.
• Stable ART regimen for minimum of 12 weeks with no detectable HIV RNA concentrations as defined above. Participants may have had one or more changes in their ART regimen during the 12 week for tolerance, or dosing simplification.
• Ability and willingness of participant to continue and be compliant with cART throughout the study.
• Plasma HIV-1 RNA below detectable limit by conventional CLIA approved assays (\<50 copies/mL) for ≥ 1 year. A single unconfirmed plasma HIV RNA \> limit of detection but \< 1000 c/mL is allowed within the 12 months prior to screening/cell donation but none in the preceding 6 months, is permitted provided that a repeat RNA was \< 20.
• Plasma HIV-1 RNA \< 50 copies/mL at screening.
• CD4+ cell count \> 350 cells/mm3 at screening.
• Karnofsky score of ≥ 50%
• No active HCV infection (measureable HCV RNA) within 90 days of cell procurement.
• No active HBV infection (measureable HBV DNA or HBVsAg+) within 90 days of cell procurement.
• All female participants participating in sexual activity that could lead to pregnancy must agree to use at least two of the following reliable methods of birth control (at least one of which is a barrier method) for at least 21 days prior to study entry, continuing and until 12 weeks after the last dose of the study product: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, Intrauterine Device, hormone-based contraceptive, tubal ligation, NuvaRing.
• All male participants participating in sexual activity that could lead to pregnancy must agree to use condoms for at least 21 days prior to study entry, continuing and until 12 weeks after the last dose of the study product.
• Ability and willingness of subject to give written informed consent.

You may not qualify if:

• Prior use of any HIV immunotherapy or vaccine within 12 months prior to Screening.
• Use of any of the following within 90 days prior to entry: immunomodulatory, cytokine, or growth stimulating factors such as systemic corticosteroids, cyclosporine, methotrexate, azathioprine, anti-CD25 antibody, IFN, interleukin-2 (IL-2), Coumadin, warfarin, or other Coumadin derivative anticoagulants.
• Patients on a CCR5 inhibitor or an entry inhibitor are not eligible for participation in the study
• Received any infusion blood product, immune globulin, or hematopoietic growth factors within 90 days prior to study entry.
• History of malignancy, immunodeficiency other than HIV, or any other condition that would make the subject unsuitable for the study in the opinion of the performance site PIs.
• Any active malignancy that may require chemotherapy or radiation therapy.
• Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) within 4 weeks prior to study entry.
• Inability to comply with study requirements, which could impact study integrity and/or safety.

Sponsors & Collaborators

• Catherine Bollard: lead

Study Sites (3)

Whitman Walker Health Research Department (Wwh)

Washington D.C., District of Columbia, 20005, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Children's National Medical Center and WHITMAN WALKER HEALTH RESEARCH DEPARTMENT (WWH)

Washington D.C., District of Columbia, 20010, United States

Location

MeSH Terms

Conditions

HIV Infections

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

Study Officials

• Michael Keller, MD

  CNMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, center for Cancer and Immunology Research

Study Record Dates

• First Submitted: March 27, 2018
• First Posted: April 3, 2018
• Study Start: March 21, 2019
• Primary Completion: September 15, 2021
• Study Completion: June 21, 2022
• Last Updated: April 29, 2025

Record last verified: 2025-04

Locations

US (3)