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Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure

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ClinicalTrials.gov Identifier: NCT02961829
Recruitment Status : Active, not recruiting
First Posted : November 11, 2016
Last Update Posted : August 2, 2018
Sponsor:
Collaborators:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Conselho Nacional de Desenvolvimento Científico e Tecnológico
ViiV Healthcare
Information provided by (Responsible Party):
Ricardo Sobhie Diaz, MD, PHD, Federal University of São Paulo

Tracking Information
First Submitted Date  ICMJE December 18, 2015
First Posted Date  ICMJE November 11, 2016
Last Update Posted Date August 2, 2018
Study Start Date  ICMJE July 2015
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2017)
  • Ultrasensitive RNA Viral load, [ Time Frame: from baseline and every 4 weeks up to 48 weeks. ]
  • Cell-associated HIV RNA [ Time Frame: from baseline and every 4 weeks up to 48 weeks. ]
  • Episomal DNA [ Time Frame: from baseline and every 4 weeks up to 48 weeks ]
  • specific HIV antibodies [ Time Frame: from baseline and every 4 weeks up to 48 weeks ]
  • CD38 and HLA-DR on CD4 and CD8+ cells [ Time Frame: from baseline and every 4 weeks up to 48 weeks ]
  • PBMC for env sequence evolution [ Time Frame: from baseline and every 4 weeks up to 48 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 9, 2016)
  • Ultrasensitive RNA Viral load, [ Time Frame: from baseline and every 4 weeks up to 48 weeks. ]
  • Cell-associated HIV RNA [ Time Frame: from baseline and every 4 weeks up to 48 weeks. ]
  • Epissomal DNA [ Time Frame: from baseline and every 4 weeks up to 48 weeks ]
  • specific HIV antibodies [ Time Frame: from baseline and every 4 weeks up to 48 weeks ]
  • CD38 and HLA-DR on CD4 and CD8+ cells [ Time Frame: from baseline and every 4 weeks up to 48 weeks ]
  • PBMC for env sequence evolution [ Time Frame: from baseline and every 4 weeks up to 48 weeks ]
Change History Complete list of historical versions of study NCT02961829 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure
Official Title  ICMJE Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure
Brief Summary It is becoming clear that a combination of interventions will be desirable to achieve HIV cure. Therefore the investigators propose a pilot proof of concept study, using combination of a number of different interventions for eradicating residual plasma viremia and decreasing HIV reservoirs. The investigators hypothesize that, (i) antiretroviral intensification using Maraviroc, and/or dolutegravir with (ii) Dendritic Cell vaccination using autologous HIV, and (iii) purging intervention using the Class III HDACs, Sirtuin-1, and (iv) decreasing the ratio of long-lived central memory (TCM)/transitional memory (TTM) CD4+ T-cells using Auranofin will provide a synergistic impact leading to a sterilizing cure of HIV infection. Results of this study may provide insightful evidence for planning the next steps using the more efficacious combination of intervention strategies towards HIV sterilizing cure.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Infection
  • HIV
Intervention  ICMJE
  • Drug: Maraviroc
    antiretroviral intensification
    Other Names:
    • Selzentry
    • Celsentri
  • Drug: Dolutegravir
    antiretroviral intensification
    Other Name: Tivicay
  • Biological: Dendritic Cell Vaccine
    Therapeutic vaccination
    Other Name: DC Vaccine
  • Drug: Auranofin
    purging
    Other Name: Gold Salt
  • Drug: Sirtuin Histone deacetylase inhibitor
    latency disruption
    Other Name: Nicotinamide
Study Arms  ICMJE
  • No Intervention: Antiretroviral Treated (ART) Group
    Five patients will receive no further intervention this group (control group)
  • Experimental: ART Intensification Group
    Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks
    Interventions:
    • Drug: Maraviroc
    • Drug: Dolutegravir
  • Experimental: ART Intensification + Nicotinamide Group
    Five patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks.
    Interventions:
    • Drug: Maraviroc
    • Drug: Dolutegravir
    • Drug: Sirtuin Histone deacetylase inhibitor
  • Experimental: ART Intensification + Auranofin Group
    Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks and the gold salt auranofin for 24 weeks.
    Interventions:
    • Drug: Maraviroc
    • Drug: Dolutegravir
    • Drug: Auranofin
  • Experimental: ART Intensification + DC vaccine Group
    Five patients will receive antiretroviral intensification with dolutegravir and for 48 weeks, and dendritic cell vaccine.
    Interventions:
    • Drug: Dolutegravir
    • Biological: Dendritic Cell Vaccine
  • Experimental: Multi Interventional Group
    Five patients will receive antiretroviral intensification with dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks, and gold salt for 24 weeks and dendritic cell vaccine.
    Interventions:
    • Drug: Dolutegravir
    • Biological: Dendritic Cell Vaccine
    • Drug: Auranofin
    • Drug: Sirtuin Histone deacetylase inhibitor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 9, 2016)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • > 18 years old Documented HIV-1 infection.
  • Has voluntarily signed ICF.
  • On HAART ≥ 2 years, without changes in the 24 weeks immediately prior to screening.
  • HIV viral load <50 copies/mL, and never > 50 copies/mL on 2 consecutive occasions in the last 2 years. CD4 count nadir.
  • > 350 cells/ mm3 Current CD4 count > 500 cells/ mm3.
  • R5 HIV-1 at Screening as defined by proviral DNA genotropism.

Exclusion Criteria:

A subject will NOT be eligible for study participation if he/she meets ANY of the following criteria:

  • Any evidence of an active AIDS-defining condition.
  • Any significant acute medical illness in the past 8 weeks.
  • Women who are pregnant or breastfeeding.
  • Use of any of the following within 90 days prior to entry: systemic cytotoxic chemotherapy; investigational agents; immunomodulators (colony-stimulating factors, growth factors, systemic corticosteroids, HIV vaccines, immune globulin, interleukins, interferons); coumadin, warfarin, or other Coumadin derivative anticoagulants. Use of an agent definitely or possibly associated with effects on QT intervals: amiodarone, arsenic trioxide, astemizole, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide, dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide, probucol, procainamide, quinidine, sotalol, sparfloxacin, terfenadine, thioridazine.
  • Receipt of compounds with HDAC inhibitor-like activity, such as valproic acid or nicotinamide within the last 30 days. Potential participants may enroll after a 30-day washout period.
  • Known hypersensitivity to the components of gold salt, nicotinamide or its analogs.
  • Hepatitis B (HBsAg +) or Hepatitis C (HCV RNA +) infection.
  • Known renal insufficiency defined as calculated creatinine clearance (Cockcroft Gault formula) <60 mL/min.
  • Subjects with a laboratory abnormality grade 3 or 4 with the following exceptions: pancreatic amylase, cholesterol, triglyceride, gamma glutamyl transpeptidase, bilirubin.
  • Any condition which, in the investigators opinion, could compromise the subject's safety or adherence to the trial protocol.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02961829
Other Study ID Numbers  ICMJE SPARC-7
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Ricardo Sobhie Diaz, MD, PHD, Federal University of São Paulo
Study Sponsor  ICMJE Federal University of São Paulo
Collaborators  ICMJE
  • Fundação de Amparo à Pesquisa do Estado de São Paulo
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • ViiV Healthcare
Investigators  ICMJE Not Provided
PRS Account Federal University of São Paulo
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP