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HIVPhase 1NCT02042248

A Phase I Study to Evaluate the Immunologic Response and Virologic Impact of AGS-004

A Phase 1 study testing AGS-004 in people with HIV, run by Cynthia L Gay, MD 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

The purpose of this study is to: find out the intensity and duration of the immune response after multiple injections of the investigational study product AGS-004 made from one's own dendritic cells and one's own strain of HIV; understand the changes in the body's HIV DNA , and HIV-1 RNA in peripheral and resting CD4+… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
HIV
What is being tested?
AGS-004
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
Mar 2014to May 2016
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

  • 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 a negative or indeterminate enzyme immunoassay (EIA) or a negative HIV RNA test within 45 days of reproducibly detectable plasma HIV RNA by amplification methods.
  • Participants in the AHI arm of this study must have initiated ART within 45 days of AHI diagnosis
  • Ages ≥ 18 to < 65 years old
  • Stable ART regimen for ≥ 6 months prior to Screening (Visit 1) 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.
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  • 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. 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, or toxicity are permitted.
  • All participants must continue cART throughout the study.
  • Plasma HIV-1 RNA below detected limit by conventional assays (limit of detection determined by assay employed: 75, 50, 40, or 20 copies/mL) for ≥ 1 year
  • A single unconfirmed plasma HIV RNA > limit of detection but < 1000 c/mL allowed if a subsequent assay was below the limit of detection; but none in the 6 months preceding the study screening visit.
  • Plasma HIV-1 RNA < 50 copies/mL at screening (Visit 1)
  • CD4 cell count ≥ 350 cells/mm3 at screening (Visit 1)
  • Availability of an adequate sample of frozen plasma (may have been thawed and re-frozen only once) drawn no more than 90 days (and preferably within 30 days) before starting ART, OR an adequate frozen sample of HIV p24 antigen-positive culture supernatant obtained from culture of resting CD4+ T cells.
  • Note: The VL documented from the pre-ART HIV plasma sample must be ≥8,000 copies/ml before commencing ART regimen (abstracted from medical records). If there is no viral load measurement associated with the pre-ART HIV plasma sample, another pre-ART VL measurement of 8,000 copies/ml can be used to accept the sample for AGS-004 manufacturing.
  • No history of auto-immune disease or auto-immune manifestations
  • No active HCV infection (measureable HCV RNA) within 90 days of eligibility visit (visit 3).
  • No active HBV infection (measureable HBV DNA or HBVsAg+) within 90 days of eligibility visit (visit 3).
  • Ability and willingness of participant to give written informed consent
  • Able and willing 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 leukapheresis
  • Able and willing to receive Intradermal (ID) injections without difficulty
  • All female study participants of childbearing potential must agree not to participate in a conception process, and, if participating in sexual activity that could lead to pregnancy, these female participants and their partners must agree to use at least two reliable forms of contraception for at least 21 days prior to study entry and for 12 weeks after the last dose of the study drug product:
  • o Acceptable forms of contraception include the following:
  • Condoms (male or female) with or without spermicidal agent
  • Diaphragm or cervical cap with spermicide
  • Intrauterine device (IUD)
  • Hormonal birth control drugs given by pills, shots, or placed on or under the skin
  • Tubal ligation
  • NuvaRing
  • Potential participant must have adequate organ function as indicated by the following laboratory values:
  • System/Laboratory Value:
  • Hematological:
  • Absolute neutrophil count (ANC): ≥1,500/mcL Platelets: ≥125,000/mcL Hemoglobin: ≥12g/dL
  • Coagulation:
  • Prothrombin Time or INR: ≤1.5x upper limit of normal (ULN)
  • Chemistry:
  • K+ levels: Within normal limits Mg++levels: ≥1.2 mEq/L but <1.5 x ULN Glucose: Screening serum glucose (fasting or non-fasting) <120 mg/dl Albumin: ≥3.3 g/dL
  • Renal:
  • Serum creatinine or calculated creatinine clearance: ≤1.5 x upper limit of normal (ULN) OR ≥ 60mL/min for potential participants with creatinine levels > 1.3 x institutional ULN
  • Hepatic:
  • Serum total bilirubin: Total bilirubin <1.8 times the upper limit of the normal range, unless history of Gilbert's disease or deemed related to treatment with atazanavir. If total bilirubin is elevated, direct bilirubin must be <2 times the ULN range.
  • AST (SGOT) and ALT (SGPT): ≤ 2.5 X ULN Alkaline Phosphatase: ≤ 2.5 X ULN NOTE: Creatinine clearance should be calculated per institutional standard.

Who cannot join

  • HIV-2 antibody positive in the absence of a positive HIV-1 Western Blot as measured at the Screening Visit (Visit 1).
  • Untreated syphilis infection (defined as a positive rapid plasma reagin (RPR) without clear documentation of treatment).
  • Received any infusion blood product, immune globulin, or hematopoetic growth factors within 90 days prior to study entry.
  • History of lymph node irradiation or dissection.
  • 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, interleukins, interleukin-2 (IL-2), hydroxyurea, thalidomide, sargramostim (granulocyte macrophage-colony stimulating factor [GM-CSF]), dinitrochlorobenzene (DNCB), thymosin alpha, thymopentin, inosiplex, polyribonucleotide, or ditiocarb sodium, coumadin, warfarin, or other Coumadin derivative anticoagulants.
  • Use of any prior HIV vaccine (prophylactic and/or therapeutic) within one year before screening (Visit 1).
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  • Prior participation in AGS-004 clinical research study.
  • Treatment interruption of ART for > 1 month since starting the ART from which pre-ART plasma sample was drawn
  • For any serious illness requiring systemic treatment or hospitalization, the participant must either complete therapy or be clinically stable on therapy, in the opinion of the site investigator, for at least 90 days prior to entry.
  • Pregnancy or breastfeeding
  • Any active malignancy that may require chemotherapy or radiation therapy.
  • Evidence of hepatic decompensation in cirrhotic participants: history of ascites, hepatic encephalopathy, or bleeding esophageal varices.
  • History or other clinical evidence of significant or unstable cardiac disease (e.g., angina, congestive heart failure, recent myocardial infarction, significant arrhythmia) or clinically significant electrocardiogram (ECG) abnormalities. Any history of cardiac rhythm disturbance requiring medical or surgical therapy.
  • Any renal disorder deemed clinically significant by the investigator.
  • History or other evidence of severe illness, malignancy, immunodeficiency other than HIV, or any other condition that would make the participant unsuitable for the study in the opinion of the investigator.
  • 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.
  • Known allergy or sensitivity to the components of the investigational immunotherapy.
  • Use of systemic corticosteroids and use of topical steroids over a total area exceeding 15 cm2 within 30 days prior to Screening or anticipated need for periodic use of corticosteroids during the study.
  • NOTE: For participants receiving ritonavir (as a booster or protease inhibitor (PI) as part of their ART regimen, the concomitant use of oral/systemic/topical/inhaled/intranasal corticosteroids is prohibited.
  • Any history of acute or chronic pancreatitis.
  • If the HIV care provider or study investigator is unable, as assessed by the study PI or protocol team, to construct a fully active alternative ART regimen based on previous resistance testing and/or treatment history.
  • Known psychiatric or substance abuse disorders that would interfere with one's ability to fully cooperate with the requirements of the trial.
  • Any investigational antiretroviral agents or use of a CCR5 inhibitor at Screening.
  • Active autoimmune disease or condition including, but not limited to:
  • Rheumatoid arthritis (RF positive arthritis with current or recent flare);
  • Inflammatory bowel disease;
  • Systemic lupus erythematosis (clinical evidence confirmed with ANA >1:80);
  • Ankylosing spondylitis; Hashimoto's disease; Scleroderma; Multiple sclerosis; Autoimmune hemolytic anemia (AHA); Immune thrombocytopenic purpura; and, Type I diabetes mellitus (insulin therapy for Type II diabetes is permitted).
  • Participation in another investigational clinical research study (with the exception of an antiretroviral treatment trial that uses FDA approved antiretroviral agents) or use of investigational agents within 30 days prior to Screening.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

Other trials in United States

About this study

Official title: IGHID 1309 -A Phase I Study to Evaluate the Kinetics of the Immunologic Response and Virologic Impact of AGS-004 in HIV-Infected Individuals Suppressed on Antiretroviral Therapy Initiated During Acute and Chronic HIV Infection

The purpose of this study is to:

  • find out the intensity and duration of the immune response after multiple injections of the investigational study product AGS-004 made from one's own dendritic cells and one's own strain of HIV;
  • understand the changes in the body's HIV DNA , and HIV-1 RNA in peripheral and resting CD4+ cells prior to and following administration of AGS- 004.
  • find out if low levels of HIV virus that are not detectable by standard HIV RNA assays will decrease following the administration of AGS-004.
  • find out if it is safe to give individuals with HIV multiple injections of AGS-004 made from the person's own dendritic cells and their own strain of HIV.
  • find out if administration of AGS-004 decreases the amount of latent HIV infection in resting CD4 cells
Read the detailed description

This is a phase I, single-site, pilot study of the kinetics of the immunological response and virological impact of AGS-004 administered in participants with durable viral suppression on ART initiated during acute (AHI) and chronic HIV infection (CHI). Patients will be screened for eligibility in Step 1. Those meeting study eligibility and with successful production of Argos (AGS)-004 product will then enter Step 2 with administration of AGS-004. All participants will continue ART throughout the study.

Conditions
HIV
Being tested
AGS-004
Keywords
HIV, Acute HIV Infection, Chronic HIV Infection, AGS-004, Phase 1, Antiretroviral Therapy, ART, UNC, Argos Therapeutics, The CARE Collaboratory of AIDS, Immunization, vaccination

What participants receive

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

  • AGS-004Biological

    All participants in both arms will receive the same treatment and doses of AGS-004 in Step 2 at weeks 0, 4, 8, and 12.

Study groups in NCT02042248
Study groupRoleWhat they receive
Arm A: ART initiated during AHIExperimentalArm A will enroll approximately 6 participants who initiated ART during AHI (acute HIV infection). The target dose of AGS -004 is delivered in three ID (intradermal) injections of 0.2 mL of AGS-004 (0.6 mL total volume) for a total of 1.2 x 107 viable cells. AGS-004 is administered every 4 weeks at weeks 0, 4, 8, and 12 for a total of 4 doses.
Receives: Biological: AGS-004
Arm B: ART initiated during CHIExperimentalArm B will enroll approximately 6 participants who initiated ART during CHI (chronic HIV infection). The target dose of AGS -004 is delivered in three ID (intradermal) injections of 0.2 mL of AGS-004 (0.6 mL total volume) for a total of 1.2 x 107 viable cells. AGS-004 is administered every 4 weeks at weeks 0, 4, 8, and 12 for a total of 4 doses.
Receives: Biological: AGS-004

What is being measured

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

  1. CD8 T cell responses

    Measure the duration of HIV-specific CD8 T cell responses by a flow cytometric assay through week 32

    Measured: 32 weeks

Secondary outcomes (2)

  1. Change in low level plasma HIV-1 RNA by single copy assay (SCA)

    The change in low level HIV -1 RNA as measured by a single copy assay following AGS-004 administration

    Measured: Weeks 0, 14 and 32

  2. Change in frequency of HIV-1 infection of resting CD4+ T cells using the viral outgrowth assay

    Change in frequency of HIV-1 infection of resting CD4+ T cells using the viral outgrowth assay following AGS-004 administration

    Measured: Weeks 0, 14 and 32

Timeline

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

  1. First posted22 Jan 2014 (estimated)
  2. Study startMar 2014
  3. Primary completionMay 2016
  4. Study completionMay 2016

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
NCT02042248
Sponsor's protocol ID
13-3613
Other IDs
DAIDS-ES 11970, 5U19AI096113-03
Status last verified
May 2017
First submitted
17 Jan 2014
Last updated
4 May 2017
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

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

  • Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, Lifton MA, Racz P, Tenner-Racz K, Dalesandro M, Scallon BJ, Ghrayeb J, Forman MA, Montefiori DC, Rieber EP, Letvin NL, Reimann KA. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science. 1999 Feb 5;283(5403):857-60. doi: 10.1126/science.283.5403.857.

    PubMed 9933172

  • Addo MM, Draenert R, Rathod A, Verrill CL, Davis BT, Gandhi RT, Robbins GK, Basgoz NO, Stone DR, Cohen DE, Johnston MN, Flynn T, Wurcel AG, Rosenberg ES, Altfeld M, Walker BD. Fully differentiated HIV-1 specific CD8+ T effector cells are more frequently detectable in controlled than in progressive HIV-1 infection. PLoS One. 2007 Mar 28;2(3):e321. doi: 10.1371/journal.pone.0000321.

    PubMed 17389912

  • Goulder PJ, Watkins DI. HIV and SIV CTL escape: implications for vaccine design. Nat Rev Immunol. 2004 Aug;4(8):630-40. doi: 10.1038/nri1417. No abstract available.

    PubMed 15286729

  • Barouch DH, Kunstman J, Kuroda MJ, Schmitz JE, Santra S, Peyerl FW, Krivulka GR, Beaudry K, Lifton MA, Gorgone DA, Montefiori DC, Lewis MG, Wolinsky SM, Letvin NL. Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes. Nature. 2002 Jan 17;415(6869):335-9. doi: 10.1038/415335a.

    PubMed 11797012

  • Vaccari M, Mattapallil J, Song K, Tsai WP, Hryniewicz A, Venzon D, Zanetti M, Reimann KA, Roederer M, Franchini G. Reduced protection from simian immunodeficiency virus SIVmac251 infection afforded by memory CD8+ T cells induced by vaccination during CD4+ T-cell deficiency. J Virol. 2008 Oct;82(19):9629-38. doi: 10.1128/JVI.00893-08. Epub 2008 Jul 30.

    PubMed 18667509

  • McNeil AC, Shupert WL, Iyasere CA, Hallahan CW, Mican JA, Davey RT Jr, Connors M. High-level HIV-1 viremia suppresses viral antigen-specific CD4(+) T cell proliferation. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13878-83. doi: 10.1073/pnas.251539598.

    PubMed 11717444

  • Younes SA, Yassine-Diab B, Dumont AR, Boulassel MR, Grossman Z, Routy JP, Sekaly RP. HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific memory CD4+ T cells endowed with proliferative capacity. J Exp Med. 2003 Dec 15;198(12):1909-22. doi: 10.1084/jem.20031598.

    PubMed 14676302

  • Lichterfeld M, Yu XG, Mui SK, Williams KL, Trocha A, Brockman MA, Allgaier RL, Waring MT, Koibuchi T, Johnston MN, Cohen D, Allen TM, Rosenberg ES, Walker BD, Altfeld M. Selective depletion of high-avidity human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells after early HIV-1 infection. J Virol. 2007 Apr;81(8):4199-214. doi: 10.1128/JVI.01388-06. Epub 2007 Feb 7.

    PubMed 17287271

  • Zanussi S, Simonelli C, D'Andrea M, Caffau C, Clerici M, Tirelli U, DePaoli P. CD8+ lymphocyte phenotype and cytokine production in long-term non-progressor and in progressor patients with HIV-1 infection. Clin Exp Immunol. 1996 Aug;105(2):220-4. doi: 10.1046/j.1365-2249.1996.d01-746.x.

    PubMed 8706325

  • Trautmann L, Janbazian L, Chomont N, Said EA, Gimmig S, Bessette B, Boulassel MR, Delwart E, Sepulveda H, Balderas RS, Routy JP, Haddad EK, Sekaly RP. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med. 2006 Oct;12(10):1198-202. doi: 10.1038/nm1482. Epub 2006 Aug 20.

    PubMed 16917489

  • Steinman RM, Banchereau J. Taking dendritic cells into medicine. Nature. 2007 Sep 27;449(7161):419-26. doi: 10.1038/nature06175.

    PubMed 17898760

  • Nicolette CA, Healey D, Tcherepanova I, Whelton P, Monesmith T, Coombs L, Finke LH, Whiteside T, Miesowicz F. Dendritic cells for active immunotherapy: optimizing design and manufacture in order to develop commercially and clinically viable products. Vaccine. 2007 Sep 27;25 Suppl 2:B47-60. doi: 10.1016/j.vaccine.2007.06.006. Epub 2007 Jun 21.

    PubMed 17669561

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AGS-004 in people with HIV, run by Cynthia L Gay, MD 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 43 inclusion and 29 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 4 May 2017. 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?

CD8 T cell responses (time frame: 32 weeks). 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 NCT02042248, which also lists 58 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 4 May 2017.

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