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

Completed · Phase 1

Conditions studied: HIV

In brief

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

Key facts

Study ID

NCT02042248

Run by

Cynthia L Gay, MD

People needed

6

Starts

2014-03-01

Expected to finish

2016-05-01

Last updated by the study team

2017-05-04

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• 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

You may not qualify if…

• 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).
• 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);

Where it is running

• University of North Carolina — Chapel Hill, North Carolina, United States

Full record on ClinicalTrials.gov

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