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Safety and Immunogenicity of a Vaccine Dendritic Cell-based Pulsed With Autologous Heat-inactivated in HIV-1 Infected Patients

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ClinicalTrials.gov Identifier: NCT02767193
Recruitment Status : Completed
First Posted : May 10, 2016
Last Update Posted : July 26, 2019
Sponsor:
Information provided by (Responsible Party):
Judit Pich Martínez, Fundacion Clinic per a la Recerca Biomédica

Tracking Information
First Submitted Date  ICMJE April 22, 2016
First Posted Date  ICMJE May 10, 2016
Last Update Posted Date July 26, 2019
Study Start Date  ICMJE May 2016
Actual Primary Completion Date May 22, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2016)
  • Number of Participants with adverse events of grade 3 or higher [ Time Frame: 28 weeks ]
    • Local adverse events of grade 3 or higher (pain and skin reactions including induration)
    • Systemic adverse events of grade 3 or higher (fever, chills, headache, nausea, vomiting, malaise and myalgia)
    • Clinical or laboratory confirmed grade 3 or higher on physical examination or retests adverse events Any event attributable to the vaccine involving a discontinuation of vaccination regime.
  • Virological [ Time Frame: 12 weeks ]
    Proportion of patients with undetectable viral load (<37 copies / mL) at 12 weeks
Original Primary Outcome Measures  ICMJE
 (submitted: May 6, 2016)
  • Number of Participants with adverse events of grade 3 or higher [ Time Frame: 28 weeks ]
    • Local adverse events of grade 3 or higher (pain and skin reactions including induration)
    • Systemic adverse events of grade 3 or higher (fever, chills, headache, nausea, vomiting, malaise and myalgia)
    • Clinical or laboratory confirmed grade 3 or higher on physical examination or retests adverse events Any event attributable to the vaccine involving a discontinuation of vaccination regime.
  • Virological [ Time Frame: 16 weeks ]
    Proportion of patients with undetectable viral load (<37 copies / mL) 12 weeks after discontinuation of antiretroviral therapy.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2016)
  • Number of adverse events grade 1 and 2 within 14 days after each immunization (weeks 2, 4 and 6) [ Time Frame: 6 weeks ]
  • Changes in the specific immune response [ Time Frame: 28 weeks ]
    Measured by ELISPOT visits in weeks 2, 4, 8, 12, 16 and 28 compared to baseline and screening for dendritic cell vaccine and pegylated interferon.
  • Changes in levels of viral reservoir. [ Time Frame: 28 weeks ]
    Measure the proviral DNA visits in the weeks -44, -36, 4, 8, 12, 16 and 28 compared to baseline and screening.
  • Proportion of patients with changes in any value of the levels of inflammatory markers, microbial translocation and immune activation [ Time Frame: 28 weeks ]
    In visits at weeks 4, 16 and 28 compared compared to baseline and screening
  • Proportion of patients with viral rebound [ Time Frame: 15 days ]
    Two consecutive obtaining measurements of plasma viral load> 37 copies / mL separated by at least 15 days after discontinuation of antiretroviral therapy.
  • Proportion of patients with autoimmunity markers induced by the vaccine as measured by: antithyroid antibodies (antithyroglobulin, antithyroid peroxidase), antinuclear antibodies, antiphospholipid antibodies and rheumatoid factors. [ Time Frame: 16 weeks ]
    Evaluation on autoimmunity with antithyroid antibodies (antithyroglobulin, antithyroid peroxidase), antinuclear antibodies, antiphospholipid antibodies and rheumatoid factor at screening, baseline and week 16.
  • Changes in the transcriptome of patients visits weeks 4, 16 and 28 compared to baseline (week -12) [ Time Frame: 28 weeks ]
    Weeks 4, 16 and 28 compared to baseline
  • Evaluation of the specific immune response trought IFN-gamma production in vitro at screening and baseline [ Time Frame: week 0 ]
    Proportion of patients with IFN-gamma production in vitro measured by ELISPOT at screening and baseline
  • Evaluation of the specific immune response thought dendritic cell maturation markers in vitro at screening and baseline [ Time Frame: week 0 ]
    Proportion of patients with dendritic cell maturation markers in vitro measured by flow cytometry at screening and baseline
  • Evaluation of the specific immune response thought T-cell proliferation in vitro at screening and baseline [ Time Frame: week 0 ]
    Proportion of patients with T-cell proliferation in vitro measured by CFSE (carboxyfluorescein succinimidyl ester) at screening and baseline
Original Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2016)
  • Number of adverse events grade 1 and 2 within 14 days after each immunization (weeks 2, 4 and 6) [ Time Frame: 6 weeks ]
  • Changes in the specific immune response [ Time Frame: 28 weeks ]
    Measured by ELISPOT visits in weeks 2, 4, 8, 12, 16 and 28 compared to baseline and screening for dendritic cell vaccine and pegylated interferon.
  • Changes in levels of viral reservoir. [ Time Frame: 28 weeks ]
    Measure the proviral DNA visits in the weeks -44, -36, 4, 8, 12, 16 and 28 compared to baseline and screening.
  • Proportion of patients with changes in any value of the levels of inflammatory markers, microbial translocation and immune activation [ Time Frame: 28 weeks ]
    In visits at weeks 4, 16 and 28 compared compared to baseline and screening
  • Proportion of patients with viral rebound [ Time Frame: 15 days ]
    Two consecutive obtaining measurements of plasma viral load> 37 copies / mL separated by at least 15 days after discontinuation of antiretroviral therapy.
  • Proportion of patients with autoimmunity markers induced by the vaccine as measured by: antithyroid antibodies (antithyroglobulin, antithyroid peroxidase), antinuclear antibodies, antiphospholipid antibodies and rheumatoid factors. [ Time Frame: 16 weeks ]
    Evaluation on autoimmunity with antithyroid antibodies (antithyroglobulin, antithyroid peroxidase), antinuclear antibodies, antiphospholipid antibodies and rheumatoid factor at screening, baseline and week 16.
  • Changes in the transcriptome of patients visits weeks 4, 16 and 28 compared to baseline (week -12) [ Time Frame: 28 weeks ]
    Weeks 4, 16 and 28 compared to baseline
  • Evaluation of the specific immune response against dendritic cells in vitro in HIV (DC maturation markers, T-cell proliferation and specific interferon-alpha production) -12 and -11 week. [ Time Frame: week 0 ]
    Evaluation of the specific immune response against dendritic cells in vitro in HIV at baseline and screening
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Immunogenicity of a Vaccine Dendritic Cell-based Pulsed With Autologous Heat-inactivated in HIV-1 Infected Patients
Official Title  ICMJE Safety and Immunogenicity of a Vaccine Dendritic Cell-based Pulsed With Autologous Heat-inactivated HIV in HIV-1 Infected Patients. Prospective, Randomized, Partially Blinded Study
Brief Summary single-center, national clinical trial, phase I, randomized (1: 1: 1: 1), prospective, placebo-controlled, partially masked, parallel group. Patients will be assigned to one of the following four arms: 3 immunizations of dendritic cells / 3 immunizations of dendritic cells with pegylated interferon + / 3 immunizations of placebo / 3 immunizations of placebo with pegylated interferon.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE HIV Infection
Intervention  ICMJE
  • Biological: DCV3

    Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus.

    Patients will receive three immunizations of dendritic cells during weeks 0, 2 and 4

  • Biological: DCV3 with PEG-INF
    Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus with PEG_INF Patients will receive three immunizations of dendritic cells during weeks 0, 2 and 4 and INF during weeks 4,5 and 6
  • Biological: Placebo
    Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded Patients will receive three immunizations saline + 1% albumin during weeks 0, 2 and 4
  • Biological: Placebo with PEG-INF
    Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded with PEG_INF Patients will receive three immunizations saline + 1% albumin during weeks 0, 2 and 4 and INF during weeks 4,5 and 6.
Study Arms  ICMJE
  • Experimental: DCV3
    Autologus differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus
    Intervention: Biological: DCV3
  • Experimental: DCV3 with PEG-INF
    Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus with PEG-INF
    Intervention: Biological: DCV3 with PEG-INF
  • Placebo Comparator: CD placebo
    Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded
    Intervention: Biological: Placebo
  • Placebo Comparator: CD placebo + PEG-INF
    Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded with PEG-INF
    Intervention: Biological: Placebo with PEG-INF
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 Completed
Actual Enrollment  ICMJE
 (submitted: July 25, 2019)
36
Original Estimated Enrollment  ICMJE
 (submitted: May 6, 2016)
32
Actual Study Completion Date  ICMJE May 22, 2019
Actual Primary Completion Date May 22, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient > 18 years of age;
  2. Voluntarily sign informed consent;
  3. Men or women with a negative pregnancy test before inclusion in the study;
  4. HIV infection tested (with positive antibodies to HIV-1 and a detectable viral load);
  5. Patient must be on stable treatment with cART at least 1 year
  6. The average of all measurements of CD4 during the year before starting cART should be equal or greater than 350 cells / mm3
  7. The number of CD4 + at enrollment must be equal or greater than 450 cells / mm3;
  8. Plasma HIV viral load undetectable at least 6 months before the inclusion in the study, at least two determinations (occasional blips above the undetectable level are allowed).

Exclusion Criteria:

  1. Treatment with suboptimal regimen (less than 3 antiretroviral drugs) before starting cART;
  2. History of C CDC events;
  3. Interruption of cART during the inclusion in the study;
  4. Pregnancy woman or becoming pregnant in the next months;
  5. Active opportunistic infections, or any active infection or cancer within 30 days prior to the screening visit;
  6. Therapy with immunomodulatory agents, including cytokines (eg IL-2) and gamma globulins or chemotherapy within 90 days prior to the screening visit;
  7. Use of anticoagulant medication;
  8. Use of any investigational drug within 90 days prior to study entry;
  9. Virological failure prior to antiretroviral treatment and / or mutations that confer resistance to antiretroviral drugs;
  10. Uncontrolled psychiatric disorder;
  11. Platelet count <80,000 / mm3;
  12. Values ??of hemoglobin <12g / dL;
  13. Patients with active uncontrolled autoimmune diseases;
  14. Using contraindicated drugs in accordance with the Summary of Product Specifications of pegylated interferon;
  15. Childbearing, or potential childbearing not using highly effective contraception;
  16. Any other problem that according to the investigator could interfere with the evaluation of the objectives.
  17. Any contraindication for the use of interferon peg in accordance with the Summary of Product Characteristics.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02767193
Other Study ID Numbers  ICMJE DCV3/RisVac04
2015-001795-22 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Judit Pich Martínez, Fundacion Clinic per a la Recerca Biomédica
Study Sponsor  ICMJE Judit Pich Martínez
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Fundacion Clinic per a la Recerca Biomédica
Verification Date July 2019

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