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Enhancement by Poly-ICLC During HIV-1 Infection (Poly-ICLC)

13 febbraio 2018 aggiornato da: Nina Bhardwaj

Simultaneous Disruption of Latency and Immune Enhancement by Poly-ICLC During HIV-1 Infection

This study involves researching new approaches to treating HIV infection. Currently, HIV infection is treated with combinations of drugs called antiretrovirals. These drugs protect cells from infection by interfering with the viruses' ability to make copies of itself by infecting new target cells. Though these drugs are very effective, they cannot cure HIV infection and must be taken each and every day at prescribed doses to maintain their beneficial effect. This research study is investigating a new approach that involves an addition to existing medications.

The study is investigating a medication called Poly-ICLC (Hiltonol®, Oncovir), which is an adjuvant. Adjuvants are medications that are designed to boost your body's immune responses resulting from a vaccine. The investigators want to test whether Poly-ICLC is an adjuvant that is effective in HIV-infected patients. A vaccine is not given in this study, but just investigating the adjuvant, Poly-ICLC, to determine whether it may be safe and useful in future vaccines that could be used to treat HIV, called therapeutic vaccines. One goal of future therapeutic vaccines is to reduce the virus that remains persistently inside of cells in a dormant or resting state despite treatment with HIV medications. This persistent pool is termed the "latent virus pool" or "viral reservoir". One tactic to reduce this viral reservoir is to first stimulate HIV to start replicating in order to force it out of hiding. Once viral replication occurs, the infected cells may then be recognized and killed by cells of the immune system. Therefore, we also want to see what effect Poly-ICLC has on the virus that lives inside of cells. Specifically, the investigators want to look at whether Poly-ICLC increases the level of virus inside your cells while also improving your immune system's responses.

The investigators are doing this research in hope to find new ways to treat HIV infection that may reduce exposure to medications that are called antiretrovirals. Antiretrovirals are medications used to treat HIV infection. They are very effective but have side effects and have to be taken each and every day and cannot cure HIV.

Panoramica dello studio

Descrizione dettagliata

Effective combination antiretroviral therapy (cART) has dramatically altered the morbidity and mortality associated with human immunodeficiency virus (HIV-1) infection. Nevertheless, the current treatment paradigm of lifelong antiviral therapy with near perfect patient adherence to avoid the emergence of drug resistant HIV remains less than ideal and this therapeutic approach has clear limitations.

In addition to long term toxicities associated with currently preferred therapies, combination therapy for HIV-1 infection cannot address the issue of viral persistence. HIV-1 persists in both blood and tissue despite long-term suppression with antiretroviral agents (ARVs). Eradication strategies for HIV-1 are likely to require a multi-faceted approach to reduce the latent reservoir, with key components focusing upon both the disruption of viral latency and the enhancement of cytotoxic T lymphocyte (CTL) function to promote killing of infected cells. In order to successfully achieve these objectives, agents that safely stimulate replication of the latent reservoir AND explore approaches to enhance HIV-specific adaptive immunity to augment CTL function must be investigated. The investigators propose that this may be accomplished with a single therapeutic modality that is devised appropriately. Certain adjuvants may possess immunostimulatory properties that trigger transient activation of viral transcription while simultaneously enhancing HIV-specific CTL function and, thus, may play an important role in such a vaccine.

Here, the investigators propose a proof of concept clinical trial to determine the ability of Poly-ICLC (Hiltonol®, Oncovir), to safely activate the latent viral reservoir and enhance innate immunity when administered to HIV-infected individuals. This randomized, double-blinded, placebo-controlled study will administer two doses of Poly-ICLC to HIV-infected individuals whom are virologically suppressed on combination anti-retroviral therapy (cART). The investigators hypothesize that Poly-ICLC will be safe and well-tolerated and will transiently disrupt viral latency while enhancing innate immune responses. Should this be the case, then Poly-ICLC would be an ideal modality to combine with a therapeutic HIV vaccine to reduce the number of latently infected CD4+ T cells in treated HIV-1 infected individuals.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

15

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

    • New York
      • New York, New York, Stati Uniti, 10065
        • The Rockefeller University Hospital

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 55 anni (Adulto)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • HIV-1 infection documented by previous HIV-1 serology or rapid test, or documented plasma HIV-1 RNA of >2000 copies/ml
  • On stable cART regimen in accordance with the DHHS "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents" with documented virologic suppression (VL<50 copies/ml) for ≥ 48 weeks.
  • Baseline cell associated HIV-1 RNA is detectable (≥10copies/µg RNA)
  • Laboratory values obtained within 30 days prior to study entry.

    • VL < 50 copies/ml
    • CD4+ T cell count > 500 cells/mm3
    • Absolute neutrophil count (ANC) ≥500/mm3
    • Hemoglobin ≥9.0 g/dL if female; 10 g/dL if male
    • Platelet count ≥75,000/mm3
    • AST (SGOT), ALT (SGPT) ≤3.5 × ULN
    • Alkaline phosphatase< 2.5 ULN
    • Total bilirubin ≤2.5 x ULN
    • Lipase ≤2.5 x ULN
    • Calculated creatinine clearance ≥70 mL/min as estimated by the Cockcroft-Gault equation:
  • For men(140-age in yrs)x(body wt in kg)÷(serum creatinine in mg/dLx72)=CrCl (mL/min)*

    *For women, multiply the result by 0.85 = CrCl (mL/min)

  • NOTE: A program to assist in calculations is available on the DMC web site at: http://www.fstrf.org/ACTG/ccc.html
  • For women of reproductive potential, negative serum or urine pregnancy test
  • Female candidates of reproductive potential is defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) or have not undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation).
  • Contraception requirements
  • Female candidates of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree that they will use at least two reliable barrier methods of contraception while receiving the protocol-specified treatments and for at least 24 weeks after completing stage I of the study.
  • Men and women aged 18-55 years.
  • Ability and willingness of subject to give written informed consent.
  • Adequate venous access for phlebotomy

Exclusion Criteria:

  • Previous immune based therapy
  • History of vascular disease including h/o coronary artery disease, angina/MI, TIA/CVA, peripheral vascular disease/claudication
  • Strong family history of cardiovascular disease
  • Hyperlipidemia requiring medication
  • Diabetes
  • History of Tobacco use (≥10 pack years)
  • HIV-related nephropathy
  • History of vascular disease including history of coronary artery disease, angina/MI, TIA/CVA, peripheral vascular disease/claudication, poorly controlled hypertension
  • Pregnancy or currently breast-feeding
  • Desire to become pregnant during the course of study
  • Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
  • Known allergy/sensitivity to study drugs or their formulations.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • History of autoimmunity
  • Chronic Hepatitis B (HepBSAg+) or C (HCV RNA positive)
  • Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical (e.g., infectious disease) illness.
  • Participation in any other clinical trial within 30 days prior to screening.
  • Receipt of routine vaccination(s) within 7 days of study entry, or anticipated receipt of routine vaccination(s) during the first 4 weeks of the study. If routine vaccinations are to be administered following the first 4 weeks of the study, they cannot be administered within 7 days prior to weeks 16 and 48 follow up visits.
  • Multi-drug resistant (MDR) HIV-1 precluding standard 3-drug therapy
  • Any other clinical conditions or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the requirements.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Doppio

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Arm A: Poly-ICLC
Arm A (N=15): Patients will receive an injection of 1.4 mg of Poly-ICLC (Hiltonol®, Oncovir) subcutaneously on day 1 and day 2.
Poly-ICLC (Hiltonol®, Oncovir) Administration - On days 1 and 2, patients randomized to this arm will be injected subcutaneously in the arm with 1.4 mg of Poly-ICLC (Hiltonol®, Oncovir). Each subject will receive a total of 2 SC doses of Poly-ICLC. The volume of each injection is 0.7ml. The investigators who are blinded will not be present at the time of injection by the study nurse.
Altri nomi:
  • Poly-ICLC (Hiltonol®, Oncovir)
Comparatore placebo: Arm B: Normal Saline
Arm B: (N=5): Patients will receive an injection of normal saline subcutaneously on day 1 and day 2.
Normal Saline - On days 1 and 2, patients randomized to this arm will be injected subcutaneously in the arm with normal saline obtained from the Rockefeller University Pharmacy. Each subject will receive a total of 2 SC doses of normal saline. The volume of each injection is 0.7ml. The investigators who are blinded will not be present at the time of injection by the study nurse.
Altri nomi:
  • Placebo

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number Participants With Adverse Events
Lasso di tempo: Up to 48 weeks
Safety measured by number of participants with adverse events.
Up to 48 weeks

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Plasma Interferon-gamma-inducible Protein-10 (IP-10) Level
Lasso di tempo: Day 2 and Day 4
One of the biomarkers of cellular immune activation and exhaustion quantified by flow cytometry. Normal range is 7.8-500 pg/ml.
Day 2 and Day 4
CD8 CD38 (Mean of Fluorescence)
Lasso di tempo: Day 8
the CD38-activation marker on CD8 T-cells (CD8/CD38).
Day 8
NK Cell Number
Lasso di tempo: at 48 weeks
Natural killer cells or NK cells are part of the innate immune defense against infection and cancer.
at 48 weeks
Percent Change in CD4+ Tcell-associated HIV-1 RNA as Compared to Baseline
Lasso di tempo: Baseline, Day 2, Day 4, Day 8, Day 28
CD4+ Tcell-associated HIV-1 RNA to determine whether Poly-ICLC disrupts viral latency in HIV-1-infected individuals on anti-retroviral therapy.Viral transcription assessed by monitoring cell associated HIV-1 RNA. Percent change compared to baseline.
Baseline, Day 2, Day 4, Day 8, Day 28

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Investigatori

  • Investigatore principale: Martin Markowitz, MD, Aaron Diamond AIDS Research Center
  • Direttore dello studio: Nina Bhardwaj, MD, PhD, Icahn School of Medicine at Mt. Sinai
  • Investigatore principale: Elizabeth Miller, MD, Icahn School of Medicine at Mount Sinai

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 aprile 2014

Completamento primario (Effettivo)

26 luglio 2016

Completamento dello studio (Effettivo)

26 luglio 2016

Date di iscrizione allo studio

Primo inviato

21 febbraio 2014

Primo inviato che soddisfa i criteri di controllo qualità

24 febbraio 2014

Primo Inserito (Stima)

25 febbraio 2014

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

13 marzo 2018

Ultimo aggiornamento inviato che soddisfa i criteri QC

13 febbraio 2018

Ultimo verificato

1 febbraio 2018

Maggiori informazioni

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Prove cliniche su HIV-1 Infected Adults With Chronic HIV-1 Infection

Prove cliniche su Arm A: Poly-ICLC

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