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Phase I Study of HIV 1 Antigen Expanded Specific T Cell Therapy (HXTC)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02208167
First Posted: August 4, 2014
Last Update Posted: September 15, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
CARE Collaboratory of AIDS Researchers for Eradication
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Cynthia L Gay, MD, University of North Carolina, Chapel Hill
  Purpose
This is a phase 1, single-site study is to evaluate the safety and immunologic and virologic efficacy of ex vivo expanded HIV-1 multi-antigen specific T-cell (HXTC) therapy in HIV-infected individuals with viral suppression on antiretroviral therapy (ART).

Condition Intervention Phase
HIV Biological: HXTC infusion Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: IGHID 1320 - A Phase I Study to Evaluate the Safety, Immunologic, and Virologic Responses of HIV-1 Antigen Expanded Specific T Cell Therapy (HXTC) as a Therapeutic Strategy in HIV-Infected Individuals Started on Antiretroviral Therapy During Acute and Chronic Infection

Resource links provided by NLM:


Further study details as provided by Cynthia L Gay, MD, University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Safety [ Time Frame: 1st day of study treatment until 28 days post last infusion ]
    Occurrence of any ≥ Grade 3 AE including signs/symptoms, lab toxicities, and/or clinical events, that are: possibly, probably or definitely related to study treatment.


Secondary Outcome Measures:
  • Secondary Safety [ Time Frame: 1st day of study treatment through Week 48 ]
    Occurrence of any ≥ Grade 3 AE including signs/symptoms, lab toxicities, and/or clinical events regardless of adjudicated relationship to study treatment.


Other Outcome Measures:
  • Immune Response [ Time Frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion ]
    Frequency of HIV-1 antigen-specific (gag, pol, nef) CD8+ T-cells by ELIspot

  • Immune Response [ Time Frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion ]
    Change in T cell responses from baseline to post-infusion, measured by frequency of cells secreting IFN-γ by multimer analysis, intracellular cytokine staining and ELIspot.

  • Immune Response [ Time Frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion ]
    Change in cytokine release as measured by multi-color flow cytometry

  • Immune Response [ Time Frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion ]
    Change in polyfunctionality of HIV-1 specific CD8+ and CD4+ T-cells

  • Immune Response [ Time Frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion ]
    Change in proportion of total and HIV-1 specific CD8+ T-cells expressing markers of immune exhaustion

  • Immune Response [ Time Frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion ]
    Change in proportion of CD28+/CD45RA- CD8+ CTL that display effector function from baseline to post-infusion, measured by multi-color flow cytometry.

  • Immune Response [ Time Frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion ]
    Change in antiviral activity of CD8 cells as measured by a viral inhibition assay

  • Immune Response [ Time Frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion ]
    Change in CTL killing of resting CD4+ T cells via a novel latency clearance assay from baseline to week 13 following administration of HXTC

  • Virologic Measures [ Time Frame: baseline, 4 and 13 weeks ]
    Change in plasma HIV-1 RNA by single copy assay (SCA)

  • Virologic Measures [ Time Frame: baseline, 4 and 13 weeks ]
    Change in frequency of HIV-1 infection of resting CD4+ T cells using the viral outgrowth assay

  • Virologic Measures [ Time Frame: baseline, 4 and 13 weeks ]
    Change in T-cell associated HIV-1 DNA

  • Virologic Measures [ Time Frame: baseline, 4 and 13 weeks ]
    Change in 2LTR circles in CD4+ T cells


Estimated Enrollment: 12
Actual Study Start Date: April 7, 2015
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Chronic HIV infection
HXTC infusion
Biological: HXTC infusion
Other Name: HIV 1 antigen expanded specific T cell
Acute HIV infection
HXTC infusion
Biological: HXTC infusion
Other Name: HIV 1 antigen expanded specific T cell

Detailed Description:

The main hypothesis of this study is that the administration of autologous ex vivo expanded HIV-specific T-cells (HXTCs) primed to recognize multiple HIV-1 antigens in HIV-infected participants who initiated ART during acute and chronic HIV infection will be safe, increase HIV-1 antigen specific T-cell immune responses and decrease low level viremia.

In addition, secondary objectives are to:

  1. Determine the feasibility of manufacturing HXTC from participants who started cART during acute and chronic HIV infection.
  2. Explore the ability of autologous ex vivo expanded HIV-1 specific T-cells (HXTC) to increase HIV-1 specific immune responses in participants initiated on cART during acute and chronic HIV infection.
  3. Explore the ability of autologous ex vivo expanded HIV-1 specific T-cells (HXTC) to impact latent HIV infection as measured by a quantitative viral outgrowth assay (QVOA) and integrated proviral DNA quantification, and low level viremia as measured by a single copy assay (SCA) in participants initiated on cART during acute and chronic HIV infection.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ≥ 18 years and ≤65 years of age
  2. Confirmation of HIV 1 infection

    • Chronic HIV infection (CHI) is defined as documentation of a positive HIV test result by any licensed ELISA test kit and 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.
    • Acute HIV infection (AHI) is defined as: 1) a negative or indeterminate enzyme immunoassay (EIA) plus a reproducibly detectable HIV by amplification methods, or 2) a positive 4th generation HIV Ag/Ab Combination assay and either a negative/indeterminate HIV rapid test or a negative/indeterminate Western blot, or 3) a negative HIV RNA test within 45 days of a positive EIA and ART initiation.

    Note: the HIV definitions above are pertinent to the time of diagnosis and treatment initiation.

  3. AHI participants are defined as HIV infected patients on suppressive ART that was initiated within 45 days of AHI diagnosis as defined in protocol section 5.1.2.
  4. CHI participants are defined as HIV infected patients who initiated ART with chronic HIV as defined in protocol section 5.1.2.
  5. 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 (defined as missing doses for more than two (2) consecutive days or more than four (4) cumulative days) in the 12 weeks prior to entry.

    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.

  6. Stable ART regimen for minimum of 3 months. NOTE: The ART regimen is defined by current treatment guidelines. Participants may have had one or more changes in their ART regimen for tolerance, change of guidelines, or dosing simplification.
  7. Ability and willingness of participant to continue cART throughout the study.
  8. Plasma HIV 1 RNA below detected limit by conventional assays (limit of detection: 75, 50, 40, or 20 copies/mL) for ˃1 year.

    A single unconfirmed plasma HIV RNA ˃ limit of detection but ˂ 1000 c/mL allowed within the prior 12 months; but none in the preceding 6 months.

  9. Plasma HIV 1 RNA ˂ 50 copies/mL at screening.
  10. CD4+ cell count ˃ 350 cells/mm3 at screening.
  11. No active HCV infection (measureable HCV RNA) within 90 days of enrollment.
  12. No active HBV infection (measureable HBV DNA or HBVsAg+) within 90 days of enrollment.
  13. 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 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.
  14. 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 and until 12 weeks after the last dose of the study product.
  15. Ability and willingness of subject to give written informed consent.
  16. Ability and willingness to provide adequate locator information.
  17. Ability and willingness to communicate effectively with study personnel; considered reliable, willing, and cooperative in terms of compliance with the Protocol requirements.
  18. Adequate vascular access for HXTC infusion and leukapheresis.
  19. Potential participant must have adequate organ function as indicated by the following laboratory values:

Absolute neutrophil count (ANC): ≥ 1,500 /mcL Platelets: ≥ 125,000 / mcL Hemoglobin: ≥ 12 g/dL

Coagulation:

Prothrombin Time or INR: ≤ 1.5 times upper limit of normal (ULN)

Chemistry K+ levels: Within normal limits

Renal:

Serum creatinine (or calculated creatinine clearance* for those with creatinine > 1.3 ULN): ≤ 1.3 times upper limit of normal (ULN); OR Creatinine clearance* ≥ 60 mL/min for potential participants with creatinine levels > 1.3 times institutional ULN

Hepatic Serum total bilirubin: Total bilirubin < 1.5 times the upper limit of the normal range. If total bilirubin is elevated, direct bilirubin must be < 2 times the ULN range.

NOTE: If participant is on an atazanavir containing therapy then a direct bilirubin should be measured instead of the total bilirubin and must be ≤ 1.0mg/dL.

AST (SGOT) and ALT (SGPT): ≤ 2.0 times ULN Alkaline Phosphatase: ≤ 2.5 times ULN

*Creatinine clearance should be calculated per institutional standard.

Exclusion Criteria:

  1. Prior use of any HIV immunotherapy or vaccine within 12 months prior to Screening.
  2. 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.
  3. Received any infusion blood product, immune globulin, or hematopoietic growth factors within 90 days prior to study entry.
  4. Pregnancy or breast-feeding.
  5. History or other evidence of severe illness, malignancy, immunodeficiency other than HIV, or any other condition that would make the subject unsuitable for the study in the opinion of the investigator.
  6. Use of topical steroids over a total area exceeding 0.5mg/kg/day within 30 days prior to Screening.
  7. Any active malignancy that may require chemotherapy or radiation therapy.
  8. Compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric illness or a physical illness, e.g., infectious disease. Prisoner recruitment and participation is not permitted.
  9. Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) within 4 weeks prior to study entry.
  10. Unable to have a person available to drive participant home at infusion visits.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02208167


Locations
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599-7030
Sponsors and Collaborators
Cynthia L Gay, MD
CARE Collaboratory of AIDS Researchers for Eradication
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Cynthia Gay, MD, MPH University of North Carolina
Principal Investigator: David Margolis, MD University of North Carolina, Chapel Hill
  More Information

Additional Information:
Publications:
Kaufmann D, Lichterfeld M, Altfeld M, al. e. Limited Durability of Immune Control following Treated Acute HIV Infection. Paper presented at: 11th Conference on Retroviruses and Opportunistic Infections; Feb 8-11, 2004; San Francisco.
Gianella S, von Wyl V, Fischer M, Niederost B, Joos B, Gunthard H, et al. Impact of early ART on proviral HIV-1 DNA and plasma viremia in acutely infected patients. In: 17th Conference on Retroviruses and Opportunistic Infections. San Francisco, CA; 2010.
Archin NM, Cheema M, Sackman R, Sugarbaker A, Scepanski J, Kuruc J, et al. Correlation of peak and duration of viremia and resting CD4+ T-Cell infection in acute HIV infection. In: 17th Conference on Retroviruses and Opportunistic Infections, Abstract 464. San Francisco, CA; 2010.

Responsible Party: Cynthia L Gay, MD, Clinical Associate Professor of Medicine, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02208167     History of Changes
Other Study ID Numbers: 14-0741
5U19AI096113-05 ( U.S. NIH Grant/Contract )
First Submitted: July 24, 2014
First Posted: August 4, 2014
Last Update Posted: September 15, 2017
Last Verified: September 2017

Keywords provided by Cynthia L Gay, MD, University of North Carolina, Chapel Hill:
Antigen Expanded Specific T Cell Therapy
HXTC
Antiretroviral Therapy
Acute HIV infection
Chronic HIV infection
Leukapheresis