Pilot Trial of the Effect of Vorinostat and AGS-004 on Persistent HIV-1 Infection

Stopped early · Phase 1

Conditions studied: HIV-1 Infection

In brief

The purpose of this research study is to 1) evaluate the safety of a series of injections with the AGS-004 product in combination with a series of Vorinostat doses and 2) to help scientists evaluate ways of reactivating latent (non-acting) HIV virus and determine if the immune system can be made stronger to eliminate the activated HIV virus.

Key facts

Study ID

NCT02707900

Run by

University of North Carolina, Chapel Hill

People needed

6

Starts

2016-03-01

Expected to finish

2018-07-11

Last updated by the study team

2019-10-07

Who can join

Age: 18 and older, up to 64. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• Confirmation of HIV-1 infection HIV infection is defined as documentation by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
• NOTE: The term "licensed" refers to a US FDA-approved kit.
• WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
• Ages ≥ 18 to < 65 years old.
• Karnofsky performance status >70.
• Ability and willingness of participant to give written informed consent. Note: Due to the lack of foreseeable benefit to study volunteers, illiterate or mentally incompetent volunteers will not be enrolled.
• Able and willing to provide adequate locator information.
• On antiretroviral therapy (ART) for at least 24 months and on potent ART for > or equal to 6 months prior to Screening (Visit 1).
• Note: Potent ART is defined by current treatment guidelines and consists of 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 24 weeks immediately prior to Screening (Visit 1). 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.
• All participants must continue cART throughout the study.
• Able and willing to adhere to protocol therapy and judged adherent to antiretroviral therapy.
• Plasma HIV-1 RNA < 50 copies/mL at screening (Visit 1).
• Plasma HIV-1 RNA< 50 copies/mL at two time points in the previous 12 months prior to study screening and never > or equal to 50 copies/mL on two consecutive time points in the last 24 months prior to screening.
• Note: A single unconfirmed plasma HIV RNA > or equal to 50 copies (c)/mL but < 1000 c/mL is allowed if a subsequent assay was < 50 c/mL but not in the 6 months preceding the study screening visit (Visit 1).
• CD4+ cell count ≥ 300 cells/mm3 at screening (Visit 1).
• No history of auto-immune disease or auto-immune manifestations.
• No active HCV infection (HCV antibody negative or no measureable HCV RNA) at or within 90 days of screening (Visit 1).
• No active HBV infection (measureable HBV DNA or HBVsAg+) at or within 90 days of screening (Visit 1).
• 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 to swallow pills without difficulty.
• Able and willing to receive Intradermal (ID) injections without difficulty.
• Women with written documentation of any of the following:
• prior hysterectomy OR bilateral oophorectomy (removal of both ovaries)
• bilateral tubal ligation or non-surgical permanent sterilization

You may not qualify if…

• Known allergy or sensitivity to the components of the investigational immunotherapy or the components of VOR or its analogs or DMSO.
• 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).
• Note: In cases of untreated syphilis, participant may re-screen following documentation of adequate treatment of syphilis
• Received any infusion blood product, immune globulin, or hematopoetic growth factors within 90 days prior to study entry.
• All women unless there is written documentation of menopause (absence of a period for ≥ one year and FSH level indicating menopause), hysterectomy, oophorectomy, or tubal ligation.
• All male participants expecting to father children within the projected duration of the study.
• Use of any of the following within 90 days prior to screening: immunomodulatory, cytokine, or growth stimulating factors such as systemic cytotoxic chemotherapy, systemic corticosteroids, immune globulin, interferon, cyclosporine, methotrexate, azathioprine, anti-CD25 antibody, IFN, interleukins, interleukin-2 (IL-2), hydroxyurea, thalidomide, sargramostim (granulocyte macrophage-colony stimulating factor [GM-CSF]), growth factors, dinitrochlorobenzene (DNCB), thymosin alpha, thymopentin, inosiplex, polyribonucleotide, or ditiocarb sodium, coumadin, warfarin, or other Coumadin derivative anticoagulants.
• Use of the following medications that carry risk of torsade des pointes: amiodarone, arsenic trioxide, astemizole, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide, dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide, probucol, procainimide, quinidine, sotalol, sparfloxacin, terfenadine, thioridazine.
• Receipt of compounds with HDAC inhibitor-like activity, such as valproic acid within 30 days prior to screening. Potential participants may enroll after a 30-day washout period.
• Use of any investigational antiretroviral agents within 30 days prior to Screening (Visit 1).
• Use of antiretroviral medications that cannot be co-administered with Vorinostat within the 4 weeks of the first dose and anytime thereafter while on the study.
• 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.
• Use of systemic corticosteroids or 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 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.
• Known history of a bone marrow disorder
• Treatment for an active AIDS-defining opportunistic infection within 90 days prior to Screening.
• Any active malignancy that may require chemotherapy or radiation therapy.
• History of lymph node irradiation or dissection.
• 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 history of acute or chronic pancreatitis.
• Any renal disorder deemed clinically significant by the investigator.
• Active autoimmune disease or condition including, but not limited to:

Where it is running

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

Full record on ClinicalTrials.gov

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