HIV-1 Infected Adults With Chronic HIV-1 InfectionPhase 1/2Poly-ICLCNCT02071095
Enhancement by Poly-ICLC During HIV-1 Infection
A Phase 1/2 study testing Arm A: Poly-ICLC and Arm B: Normal Saline in people with HIV-1 Infected Adults With Chronic HIV-1 Infection, run by Nina Bhardwaj at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- HIV-1 Infected Adults With Chronic HIV-1 Infection
- What is being tested?
- Arm A: Poly-ICLC and Arm B: Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to 26 Jul 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 24Show fewer
- 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
Who cannot join
- 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)
Show all 20Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Rockefeller University Hospital
New York, New York, 10065
About this study
Official title: 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.
Read the detailed description
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.
- Being tested
- Arm A: Poly-ICLC, Arm B: Normal Saline
- Keywords
- Human immunodeficiency virus 1, Combined Antiretroviral Therapy, Poly-ICLC, Adjuvant
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm A: Poly-ICLCDrug
Also called Poly-ICLC (Hiltonol®, Oncovir)
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.
Arm B: Normal SalineDrug
Also called Placebo
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Poly-ICLC | Experimental | 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. Receives: Drug: Arm A: Poly-ICLC |
| Arm B: Normal Saline | Placebo comparator | Arm B: (N=5): Patients will receive an injection of normal saline subcutaneously on day 1 and day 2. Receives: Drug: Arm B: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number Participants With Adverse Events
Safety measured by number of participants with adverse events.
Measured: Up to 48 weeks
Secondary outcomes (4)
Plasma Interferon-gamma-inducible Protein-10 (IP-10) Level
One of the biomarkers of cellular immune activation and exhaustion quantified by flow cytometry. Normal range is 7.8-500 pg/ml.
Measured: Day 2 and Day 4
CD8 CD38 (Mean of Fluorescence)
the CD38-activation marker on CD8 T-cells (CD8/CD38).
Measured: Day 8
NK Cell Number
Natural killer cells or NK cells are part of the innate immune defense against infection and cancer.
Measured: at 48 weeks
Percent Change in CD4+ Tcell-associated HIV-1 RNA as Compared to Baseline
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.
Measured: Baseline, Day 2, Day 4, Day 8, Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2014 (estimated)
- Study startApr 2014
- Primary completion26 Jul 2016
- Study completion26 Jul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (50)Papers the sponsor has linked to this study.
- Other trials for HIV-1 Infected Adults With Chronic HIV-1 InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nina Bhardwaj
- Sponsor type
- University, hospital or other
- Collaborators
- The Campbell Foundation, Oncovir, Inc., National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
- Responsible party
- Sponsor-investigator, Nina Bhardwaj, Icahn School of Medicine at Mount Sinai
- Investigators
- Nina Bhardwaj, MD, PhD, Study director, Icahn School of Medicine at Mt. SinaiElizabeth Miller, MD, Principal investigator, Icahn School of Medicine at Mount SinaiMartin Markowitz, MD, Principal investigator, Aaron Diamond AIDS Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02071095
- Sponsor's protocol ID
- GCO 13-0482
- Other IDs
- Campbell Foundation, 1R21AI110736-01
- Acronym
- Poly-ICLC
- Status last verified
- Feb 2018
- First submitted
- 21 Feb 2014
- Last updated
- 13 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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 22837004Shan 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 22406268Xing S, Bullen CK, Shroff NS, Shan L, Yang HC, Manucci JL, Bhat S, Zhang H, Margolick JB, Quinn TC, Margolis DM, Siliciano JD, Siliciano RF. Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation. J Virol. 2011 Jun;85(12):6060-4. doi: 10.1128/JVI.02033-10. Epub 2011 Apr 6.
PubMed 21471244Xing S, Siliciano RF. Targeting HIV latency: pharmacologic strategies toward eradication. Drug Discov Today. 2013 Jun;18(11-12):541-51. doi: 10.1016/j.drudis.2012.12.008. Epub 2012 Dec 25.
PubMed 23270785Elliot, J., et al. The Safety and Effect of Multiple Doses of Vorinostat on HIV Transcription in HIV+ Patients Receiving cART. in Conference on Retroviruses and Opportunistic Infections (CROI) (2013).
Almeida M, Cordero M, Almeida J, Orfao A. Different subsets of peripheral blood dendritic cells show distinct phenotypic and functional abnormalities in HIV-1 infection. AIDS. 2005 Feb 18;19(3):261-71.
PubMed 15718836Almeida M, Cordero M, Almeida J, Orfao A. Persistent abnormalities in peripheral blood dendritic cells and monocytes from HIV-1-positive patients after 1 year of antiretroviral therapy. J Acquir Immune Defic Syndr. 2006 Apr 1;41(4):405-15. doi: 10.1097/01.qai.0000209896.82255.d3.
PubMed 16652047Almeida M, Cordero M, Almeida J, Orfao A. Abnormal cytokine production by circulating monocytes and dendritic cells of myeloid origin in ART-treated HIV-1+ patients relates to CD4+ T-cell recovery and HCV co-infection. Curr HIV Res. 2007 May;5(3):325-36. doi: 10.2174/157016207780636524.
PubMed 17504174Anthony DD, Yonkers NL, Post AB, Asaad R, Heinzel FP, Lederman MM, Lehmann PV, Valdez H. Selective impairments in dendritic cell-associated function distinguish hepatitis C virus and HIV infection. J Immunol. 2004 Apr 15;172(8):4907-16. doi: 10.4049/jimmunol.172.8.4907.
PubMed 15067070Buisson S, Benlahrech A, Gazzard B, Gotch F, Kelleher P, Patterson S. Monocyte-derived dendritic cells from HIV type 1-infected individuals show reduced ability to stimulate T cells and have altered production of interleukin (IL)-12 and IL-10. J Infect Dis. 2009 Jun 15;199(12):1862-71. doi: 10.1086/599122.
PubMed 19419334Chang JJ, Lacas A, Lindsay RJ, Doyle EH, Axten KL, Pereyra F, Rosenberg ES, Walker BD, Allen TM, Altfeld M. Differential regulation of toll-like receptor pathways in acute and chronic HIV-1 infection. AIDS. 2012 Mar 13;26(5):533-41. doi: 10.1097/QAD.0b013e32834f3167.
PubMed 22210629Fan Z, Huang XL, Kalinski P, Young S, Rinaldo CR Jr. Dendritic cell function during chronic hepatitis C virus and human immunodeficiency virus type 1 infection. Clin Vaccine Immunol. 2007 Sep;14(9):1127-37. doi: 10.1128/CVI.00141-07. Epub 2007 Jul 18.
PubMed 17634507Granelli-Piperno A, Golebiowska A, Trumpfheller C, Siegal FP, Steinman RM. HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation. Proc Natl Acad Sci U S A. 2004 May 18;101(20):7669-74. doi: 10.1073/pnas.0402431101. Epub 2004 May 5.
PubMed 15128934Hodges A, Sharrocks K, Edelmann M, Baban D, Moris A, Schwartz O, Drakesmith H, Davies K, Kessler B, McMichael A, Simmons A. Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication. Nat Immunol. 2007 Jun;8(6):569-77. doi: 10.1038/ni1470. Epub 2007 May 13.
PubMed 17496896Lester RT, Yao XD, Ball TB, McKinnon LR, Kaul R, Wachihi C, Jaoko W, Plummer FA, Rosenthal KL. Toll-like receptor expression and responsiveness are increased in viraemic HIV-1 infection. AIDS. 2008 Mar 30;22(6):685-94. doi: 10.1097/QAD.0b013e3282f4de35.
PubMed 18356597
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Simultaneous Disruption of Latency and Immune Enhancement by Poly-ICLC During HIV-1 Infection
- ClinicalTrials.gov ID
- NCT02071095
- Acronym / sponsor ID
- Poly-ICLC / GCO 13-0482
- Keywords
- Human immunodeficiency virus 1, Combined Antiretroviral Therapy, Poly-ICLC, Adjuvant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Nina BhardwajUniversity, hospital or other
- Collaborators
- The Campbell Foundation, Oncovir, Inc., National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Apr 2014
- Primary completion
- 26 Jul 2016 (actual)
- Study completion
- 26 Jul 2016 (actual)
- First posted
- 25 Feb 2014 (estimated)
- Results
- Posted 13 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Poly-ICLC | Experimental | Drug: Arm A: Poly-ICLCArm A (N=15): Patients will receive an injection of 1.4 mg of Poly-ICLC (Hiltonol®, Oncovir) subcutaneously on day 1 and day 2. |
| Arm B: Normal Saline | Placebo comparator | Drug: Arm B: Normal SalineArm B: (N=5): Patients will receive an injection of normal saline subcutaneously on day 1 and day 2. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (24 listed)
- 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.
- For men(140-age in yrs)x(body wt in kg)÷(serum creatinine in mg/dLx72)=CrCl (mL/min)*
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arm A: Poly-ICLCAlso: Poly-ICLC (Hiltonol®, Oncovir)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. | Drug | Arm A: Poly-ICLC |
| Arm B: Normal SalineAlso: PlaceboNormal 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. | Drug | Arm B: Normal Saline |
Primary outcome
Number Participants With Adverse Events
Time frame: Up to 48 weeks
Safety measured by number of participants with adverse events.
4 secondary outcomes
Plasma Interferon-gamma-inducible Protein-10 (IP-10) Level
Time frame: Day 2 and Day 4
CD8 CD38 (Mean of Fluorescence)
Time frame: Day 8
NK Cell Number
Time frame: at 48 weeks
Percent Change in CD4+ Tcell-associated HIV-1 RNA as Compared to Baseline
Time frame: Baseline, Day 2, Day 4, Day 8, Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22837004Archin 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.
- Background: PubMed 22406268Shan 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.
- Background: PubMed 21471244Xing S, Bullen CK, Shroff NS, Shan L, Yang HC, Manucci JL, Bhat S, Zhang H, Margolick JB, Quinn TC, Margolis DM, Siliciano JD, Siliciano RF. Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation. J Virol. 2011 Jun;85(12):6060-4. doi: 10.1128/JVI.02033-10. Epub 2011 Apr 6.
- Background: PubMed 23270785Xing S, Siliciano RF. Targeting HIV latency: pharmacologic strategies toward eradication. Drug Discov Today. 2013 Jun;18(11-12):541-51. doi: 10.1016/j.drudis.2012.12.008. Epub 2012 Dec 25.
- BackgroundElliot, J., et al. The Safety and Effect of Multiple Doses of Vorinostat on HIV Transcription in HIV+ Patients Receiving cART. in Conference on Retroviruses and Opportunistic Infections (CROI) (2013).
- Background: PubMed 15718836Almeida M, Cordero M, Almeida J, Orfao A. Different subsets of peripheral blood dendritic cells show distinct phenotypic and functional abnormalities in HIV-1 infection. AIDS. 2005 Feb 18;19(3):261-71.
- Background: PubMed 16652047Almeida M, Cordero M, Almeida J, Orfao A. Persistent abnormalities in peripheral blood dendritic cells and monocytes from HIV-1-positive patients after 1 year of antiretroviral therapy. J Acquir Immune Defic Syndr. 2006 Apr 1;41(4):405-15. doi: 10.1097/01.qai.0000209896.82255.d3.
- Background: PubMed 17504174Almeida M, Cordero M, Almeida J, Orfao A. Abnormal cytokine production by circulating monocytes and dendritic cells of myeloid origin in ART-treated HIV-1+ patients relates to CD4+ T-cell recovery and HCV co-infection. Curr HIV Res. 2007 May;5(3):325-36. doi: 10.2174/157016207780636524.
- Background: PubMed 15067070Anthony DD, Yonkers NL, Post AB, Asaad R, Heinzel FP, Lederman MM, Lehmann PV, Valdez H. Selective impairments in dendritic cell-associated function distinguish hepatitis C virus and HIV infection. J Immunol. 2004 Apr 15;172(8):4907-16. doi: 10.4049/jimmunol.172.8.4907.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nina Bhardwaj, MD, PhD study director
Icahn School of Medicine at Mt. Sinai
Elizabeth Miller, MD principal investigator
Icahn School of Medicine at Mount Sinai
Martin Markowitz, MD principal investigator
Aaron Diamond AIDS Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Arm A: Poly-ICLC and Arm B: Normal Saline in people with HIV-1 Infected Adults With Chronic HIV-1 Infection, run by Nina Bhardwaj 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 24 inclusion and 20 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 13 Mar 2018. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number Participants With Adverse Events (time frame: Up to 48 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 NCT02071095, which also lists 50 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 13 Mar 2018.