Back to resultsSafety and Immunogenicity of a Vaccine Dendritic Cell-based Pulsed With Autologous Heat-inactivated in HIV-1 Infected Patients
Primary Purpose
HIV Infection
Status
Completed
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
DCV3
DCV3 with PEG-INF
Placebo
Placebo with PEG-INF
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infection
Eligibility Criteria
Inclusion Criteria:
- Patient > 18 years of age;
- Voluntarily sign informed consent;
- Men or women with a negative pregnancy test before inclusion in the study;
- HIV infection tested (with positive antibodies to HIV-1 and a detectable viral load);
- Patient must be on stable treatment with cART at least 1 year
- The average of all measurements of CD4 during the year before starting cART should be equal or greater than 350 cells / mm3
- The number of CD4 + at enrollment must be equal or greater than 450 cells / mm3;
- 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:
- Treatment with suboptimal regimen (less than 3 antiretroviral drugs) before starting cART;
- History of C CDC events;
- Interruption of cART during the inclusion in the study;
- Pregnancy woman or becoming pregnant in the next months;
- Active opportunistic infections, or any active infection or cancer within 30 days prior to the screening visit;
- Therapy with immunomodulatory agents, including cytokines (eg IL-2) and gamma globulins or chemotherapy within 90 days prior to the screening visit;
- Use of anticoagulant medication;
- Use of any investigational drug within 90 days prior to study entry;
- Virological failure prior to antiretroviral treatment and / or mutations that confer resistance to antiretroviral drugs;
- Uncontrolled psychiatric disorder;
- Platelet count <80,000 / mm3;
- Values ??of hemoglobin <12g / dL;
- Patients with active uncontrolled autoimmune diseases;
- Using contraindicated drugs in accordance with the Summary of Product Specifications of pegylated interferon;
- Childbearing, or potential childbearing not using highly effective contraception;
- Any other problem that according to the investigator could interfere with the evaluation of the objectives.
- Any contraindication for the use of interferon peg in accordance with the Summary of Product Characteristics.
Sites / Locations
- Hospital Clínic
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Arm Label
DCV3
DCV3 with PEG-INF
CD placebo
CD placebo + PEG-INF
Arm Description
Autologus differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus
Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus with PEG-INF
Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded
Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded with PEG-INF
Outcomes
Primary Outcome Measures
Number of Participants with adverse events of grade 3 or higher
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
Proportion of patients with undetectable viral load (<37 copies / mL) at 12 weeks
Secondary Outcome Measures
Number of adverse events grade 1 and 2 within 14 days after each immunization (weeks 2, 4 and 6)
Changes in the specific immune response
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.
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
In visits at weeks 4, 16 and 28 compared compared to baseline and screening
Proportion of patients with viral rebound
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.
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)
Weeks 4, 16 and 28 compared to baseline
Evaluation of the specific immune response trought IFN-gamma production in vitro at screening and baseline
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
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
Proportion of patients with T-cell proliferation in vitro measured by CFSE (carboxyfluorescein succinimidyl ester) at screening and baseline
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02767193
Brief Title
Safety and Immunogenicity of a Vaccine Dendritic Cell-based Pulsed With Autologous Heat-inactivated in HIV-1 Infected Patients
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
May 2016 (undefined)
Primary Completion Date
May 22, 2019 (Actual)
Study Completion Date
May 22, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Judit Pich Martínez
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DCV3
Arm Type
Experimental
Arm Description
Autologus differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus
Arm Title
DCV3 with PEG-INF
Arm Type
Experimental
Arm Description
Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus with PEG-INF
Arm Title
CD placebo
Arm Type
Placebo Comparator
Arm Description
Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded
Arm Title
CD placebo + PEG-INF
Arm Type
Placebo Comparator
Arm Description
Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded with PEG-INF
Intervention Type
Biological
Intervention Name(s)
DCV3
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
DCV3 with PEG-INF
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
Placebo with PEG-INF
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants with adverse events of grade 3 or higher
Description
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.
Time Frame
28 weeks
Title
Virological
Description
Proportion of patients with undetectable viral load (<37 copies / mL) at 12 weeks
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Number of adverse events grade 1 and 2 within 14 days after each immunization (weeks 2, 4 and 6)
Time Frame
6 weeks
Title
Changes in the specific immune response
Description
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.
Time Frame
28 weeks
Title
Changes in levels of viral reservoir.
Description
Measure the proviral DNA visits in the weeks -44, -36, 4, 8, 12, 16 and 28 compared to baseline and screening.
Time Frame
28 weeks
Title
Proportion of patients with changes in any value of the levels of inflammatory markers, microbial translocation and immune activation
Description
In visits at weeks 4, 16 and 28 compared compared to baseline and screening
Time Frame
28 weeks
Title
Proportion of patients with viral rebound
Description
Two consecutive obtaining measurements of plasma viral load> 37 copies / mL separated by at least 15 days after discontinuation of antiretroviral therapy.
Time Frame
15 days
Title
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.
Description
Evaluation on autoimmunity with antithyroid antibodies (antithyroglobulin, antithyroid peroxidase), antinuclear antibodies, antiphospholipid antibodies and rheumatoid factor at screening, baseline and week 16.
Time Frame
16 weeks
Title
Changes in the transcriptome of patients visits weeks 4, 16 and 28 compared to baseline (week -12)
Description
Weeks 4, 16 and 28 compared to baseline
Time Frame
28 weeks
Title
Evaluation of the specific immune response trought IFN-gamma production in vitro at screening and baseline
Description
Proportion of patients with IFN-gamma production in vitro measured by ELISPOT at screening and baseline
Time Frame
week 0
Title
Evaluation of the specific immune response thought dendritic cell maturation markers in vitro at screening and baseline
Description
Proportion of patients with dendritic cell maturation markers in vitro measured by flow cytometry at screening and baseline
Time Frame
week 0
Title
Evaluation of the specific immune response thought T-cell proliferation in vitro at screening and baseline
Description
Proportion of patients with T-cell proliferation in vitro measured by CFSE (carboxyfluorescein succinimidyl ester) at screening and baseline
Time Frame
week 0
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient > 18 years of age;
Voluntarily sign informed consent;
Men or women with a negative pregnancy test before inclusion in the study;
HIV infection tested (with positive antibodies to HIV-1 and a detectable viral load);
Patient must be on stable treatment with cART at least 1 year
The average of all measurements of CD4 during the year before starting cART should be equal or greater than 350 cells / mm3
The number of CD4 + at enrollment must be equal or greater than 450 cells / mm3;
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:
Treatment with suboptimal regimen (less than 3 antiretroviral drugs) before starting cART;
History of C CDC events;
Interruption of cART during the inclusion in the study;
Pregnancy woman or becoming pregnant in the next months;
Active opportunistic infections, or any active infection or cancer within 30 days prior to the screening visit;
Therapy with immunomodulatory agents, including cytokines (eg IL-2) and gamma globulins or chemotherapy within 90 days prior to the screening visit;
Use of anticoagulant medication;
Use of any investigational drug within 90 days prior to study entry;
Virological failure prior to antiretroviral treatment and / or mutations that confer resistance to antiretroviral drugs;
Uncontrolled psychiatric disorder;
Platelet count <80,000 / mm3;
Values ??of hemoglobin <12g / dL;
Patients with active uncontrolled autoimmune diseases;
Using contraindicated drugs in accordance with the Summary of Product Specifications of pegylated interferon;
Childbearing, or potential childbearing not using highly effective contraception;
Any other problem that according to the investigator could interfere with the evaluation of the objectives.
Any contraindication for the use of interferon peg in accordance with the Summary of Product Characteristics.
Facility Information:
Facility Name
Hospital Clínic
City
Barcelona
State/Province
España
ZIP/Postal Code
08036
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
34858423
Citation
Leal L, Couto E, Sanchez-Palomino S, Climent N, Fernandez I, Miralles L, Romero Y, Gonzalez T, Maleno MJ, Pano B, Pich J, Nicolau C, Gatell JM, Plana M, Garcia F; DCV3-RISVAC04 Study Group. Effect of Intranodally Administered Dendritic Cell-Based HIV Vaccine in Combination With Pegylated Interferon alpha-2a on Viral Control Following ART Discontinuation: A Phase 2A Randomized Clinical Trial. Front Immunol. 2021 Nov 11;12:767370. doi: 10.3389/fimmu.2021.767370. eCollection 2021.
Results Reference
derived
Learn more about this trial
Safety and Immunogenicity of a Vaccine Dendritic Cell-based Pulsed With Autologous Heat-inactivated in HIV-1 Infected Patients
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