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HIVPhase 1HXTCNCT02208167

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

A Phase 1 study testing HXTC infusion in people with HIV, run by University of North Carolina, Chapel Hill at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
HIV
What is being tested?
HXTC infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
7 Apr 2015to 27 Nov 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 18 years and ≤65 years of age
  • 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.
  • 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.
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  • CHI participants are defined as HIV infected patients who initiated ART with chronic HIV as defined in protocol section 5.1.2.
  • 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.
  • 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.
  • Ability and willingness of participant to continue cART throughout the study.
  • 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.
  • Plasma HIV 1 RNA ˂ 50 copies/mL at screening.
  • CD4+ cell count ˃ 350 cells/mm3 at screening.
  • No active HCV infection (measureable HCV RNA) within 90 days of enrollment.
  • No active HBV infection (measureable HBV DNA or HBVsAg+) within 90 days of enrollment.
  • 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.
  • 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.
  • Ability and willingness of subject to give written informed consent.
  • Ability and willingness to provide adequate locator information.
  • Ability and willingness to communicate effectively with study personnel; considered reliable, willing, and cooperative in terms of compliance with the Protocol requirements.
  • Adequate vascular access for HXTC infusion and leukapheresis.
  • 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.

Who cannot join

  • 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.
  • Received any infusion blood product, immune globulin, or hematopoietic growth factors within 90 days prior to study entry.
  • Pregnancy or breast-feeding.
  • 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.
  • Use of topical steroids over a total area exceeding 0.5mg/kg/day within 30 days prior to Screening.
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  • Any active malignancy that may require chemotherapy or radiation therapy.
  • 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.
  • Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) within 4 weeks prior to study entry.
  • Unable to have a person available to drive participant home at infusion visits.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of North Carolina

    Chapel Hill, North Carolina, 27599-7030

Other trials in United States

About this study

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

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).

Read the 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.
Conditions
HIV
Being tested
HXTC infusion
Keywords
Antigen Expanded Specific T Cell Therapy, HXTC, Antiretroviral Therapy, Acute HIV infection, Chronic HIV infection, Leukapheresis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HXTC infusionBiological

    Also called HIV 1 antigen expanded specific T cell

Study groups in NCT02208167
Study groupRoleWhat they receive
Chronic HIV infectionOtherHXTC infusion
Receives: Biological: HXTC infusion
Acute HIV infectionOtherHXTC infusion
Receives: Biological: HXTC infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety

    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.

    Measured: 1st day of study treatment until 28 days post last infusion

Secondary outcomes (1)

  1. Secondary Safety

    Occurrence of any ≥ Grade 3 AE including signs/symptoms, lab toxicities, and/or clinical events regardless of adjudicated relationship to study treatment.

    Measured: 1st day of study treatment through Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2014 (estimated)
  2. Study start7 Apr 2015
  3. Primary completion19 Jan 2017
  4. Study completion27 Nov 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02208167
Sponsor's protocol ID
14-0741
Other IDs
5U19AI096113-05
Acronym
HXTC
Status last verified
Feb 2018
First submitted
24 Jul 2014
Last updated
7 Oct 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, Chadwick K, Margolick J, Brookmeyer R, Gallant J, Markowitz M, Ho DD, Richman DD, Siliciano RF. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997 Nov 14;278(5341):1295-300. doi: 10.1126/science.278.5341.1295.

    PubMed 9360927

  • Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, Smith K, Lisziewicz J, Lori F, Flexner C, Quinn TC, Chaisson RE, Rosenberg E, Walker B, Gange S, Gallant J, Siliciano RF. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med. 1999 May;5(5):512-7. doi: 10.1038/8394.

    PubMed 10229227

  • Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13193-7. doi: 10.1073/pnas.94.24.13193.

    PubMed 9371822

  • Barouch DH, Santra S, Schmitz JE, Kuroda MJ, Fu TM, Wagner W, Bilska M, Craiu A, Zheng XX, Krivulka GR, Beaudry K, Lifton MA, Nickerson CE, Trigona WL, Punt K, Freed DC, Guan L, Dubey S, Casimiro D, Simon A, Davies ME, Chastain M, Strom TB, Gelman RS, Montefiori DC, Lewis MG, Emini EA, Shiver JW, Letvin NL. Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. Science. 2000 Oct 20;290(5491):486-92. doi: 10.1126/science.290.5491.486.

    PubMed 11039923

  • Amara RR, Villinger F, Altman JD, Lydy SL, O'Neil SP, Staprans SI, Montefiori DC, Xu Y, Herndon JG, Wyatt LS, Candido MA, Kozyr NL, Earl PL, Smith JM, Ma HL, Grimm BD, Hulsey ML, Miller J, McClure HM, McNicholl JM, Moss B, Robinson HL. Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science. 2001 Apr 6;292(5514):69-74. doi: 10.1126/science.1058915.

    PubMed 11393868

  • Rose NF, Marx PA, Luckay A, Nixon DF, Moretto WJ, Donahoe SM, Montefiori D, Roberts A, Buonocore L, Rose JK. An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants. Cell. 2001 Sep 7;106(5):539-49. doi: 10.1016/s0092-8674(01)00482-2.

    PubMed 11551502

  • Shiver JW, Fu TM, Chen L, Casimiro DR, Davies ME, Evans RK, Zhang ZQ, Simon AJ, Trigona WL, Dubey SA, Huang L, Harris VA, Long RS, Liang X, Handt L, Schleif WA, Zhu L, Freed DC, Persaud NV, Guan L, Punt KS, Tang A, Chen M, Wilson KA, Collins KB, Heidecker GJ, Fernandez VR, Perry HC, Joyce JG, Grimm KM, Cook JC, Keller PM, Kresock DS, Mach H, Troutman RD, Isopi LA, Williams DM, Xu Z, Bohannon KE, Volkin DB, Montefiori DC, Miura A, Krivulka GR, Lifton MA, Kuroda MJ, Schmitz JE, Letvin NL, Caulfield MJ, Bett AJ, Youil R, Kaslow DC, Emini EA. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature. 2002 Jan 17;415(6869):331-5. doi: 10.1038/415331a.

    PubMed 11797011

  • Autran B, Murphy RL, Costagliola D, Tubiana R, Clotet B, Gatell J, Staszewski S, Wincker N, Assoumou L, El-Habib R, Calvez V, Walker B, Katlama C; ORVACS Study Group. Greater viral rebound and reduced time to resume antiretroviral therapy after therapeutic immunization with the ALVAC-HIV vaccine (vCP1452). AIDS. 2008 Jul 11;22(11):1313-22. doi: 10.1097/QAD.0b013e3282fdce94.

    PubMed 18580611

  • Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, Parker DC, Anderson EM, Kearney MF, Strain MC, Richman DD, Hudgens MG, Bosch RJ, Coffin JM, Eron JJ, Hazuda DJ, Margolis DM. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature. 2012 Jul 25;487(7408):482-5. doi: 10.1038/nature11286.

    PubMed 22837004

  • Shan L, Deng K, Shroff NS, Durand CM, Rabi SA, Yang HC, Zhang H, Margolick JB, Blankson JN, Siliciano RF. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity. 2012 Mar 23;36(3):491-501. doi: 10.1016/j.immuni.2012.01.014. Epub 2012 Mar 8.

    PubMed 22406268

  • Rosenberg ES, Altfeld M, Poon SH, Phillips MN, Wilkes BM, Eldridge RL, Robbins GK, D'Aquila RT, Goulder PJ, Walker BD. Immune control of HIV-1 after early treatment of acute infection. Nature. 2000 Sep 28;407(6803):523-6. doi: 10.1038/35035103.

    PubMed 11029005

  • 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.

  • Carcelain G, Tubiana R, Samri A, Calvez V, Delaugerre C, Agut H, Katlama C, Autran B. Transient mobilization of human immunodeficiency virus (HIV)-specific CD4 T-helper cells fails to control virus rebounds during intermittent antiretroviral therapy in chronic HIV type 1 infection. J Virol. 2001 Jan;75(1):234-41. doi: 10.1128/JVI.75.1.234-241.2001.

    PubMed 11119593

  • Davey RT Jr, Bhat N, Yoder C, Chun TW, Metcalf JA, Dewar R, Natarajan V, Lempicki RA, Adelsberger JW, Miller KD, Kovacs JA, Polis MA, Walker RE, Falloon J, Masur H, Gee D, Baseler M, Dimitrov DS, Fauci AS, Lane HC. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15109-14. doi: 10.1073/pnas.96.26.15109.

    PubMed 10611346

  • Appay V, Nixon DF, Donahoe SM, Gillespie GM, Dong T, King A, Ogg GS, Spiegel HM, Conlon C, Spina CA, Havlir DV, Richman DD, Waters A, Easterbrook P, McMichael AJ, Rowland-Jones SL. HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function. J Exp Med. 2000 Jul 3;192(1):63-75. doi: 10.1084/jem.192.1.63.

    PubMed 10880527

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HXTC infusion in people with HIV, run by University of North Carolina, Chapel Hill at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety (time frame: 1st day of study treatment until 28 days post last infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02208167, which also lists 55 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2019.

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