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

U.S. FDA Resources

Estimated Enrollment:	12
Study Start Date:	January 2015
Estimated Study Completion Date:	September 2018
Estimated Primary Completion Date:	September 2017 (Final data collection date for primary outcome measure)

Detailed Description:

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.

Cynthia L Gay, MD

CARE Collaboratory of AIDS Researchers for Eradication

National Institutes of Health (NIH)

National Institute of Allergy and Infectious Diseases (NIAID)

University of North Carolina 

Antigen Expanded Specific T Cell Therapy HXTC Antiretroviral Therapy	Acute HIV infection Chronic HIV infection Leukapheresis