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

Phase 1

Completed

• Conditions: HIV Infection
• Interventions: Biological: Placebo; Biological: DCV3; Biological: DCV3 with PEG-INF; Biological: Placebo with PEG-INF

• Registration Number: NCT02767193
• Lead Sponsor: Judit Pich Martínez

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 available

Study Timeline

• Study First Submitted: 2016-04-22
• Study Start: 2016-05
• Study First Submitted QC: 2016-05-06
• Study First Posted: 2016-05-10
• Primary Completion: 2019-05-22
• Study Completion: 2019-05-22
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-25
• Last Update Posted: 2019-07-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CD placebo	Placebo	Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded
DCV3	DCV3	Autologus differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus
DCV3 with PEG-INF	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
CD placebo + PEG-INF	Placebo with PEG-INF	Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded with PEG-INF

Primary Outcome Measures

Name	Time	Method
Virological	12 weeks	Proportion of patients with undetectable viral load (\<37 copies / mL) at 12 weeks
Number of Participants with adverse events of grade 3 or higher	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.

Secondary Outcome Measures

Name	Time	Method
Number of adverse events grade 1 and 2 within 14 days after each immunization (weeks 2, 4 and 6)	6 weeks
Changes in the specific immune response	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.	28 weeks	Measure the proviral DNA visits in the weeks -44, -36, 4, 8, 12, 16 and 28 compared to baseline and screening.
Evaluation of the specific immune response trought IFN-gamma production in vitro at screening and baseline	week 0	Proportion of patients with IFN-gamma production in vitro measured by ELISPOT at screening and baseline
Proportion of patients with changes in any value of the levels of inflammatory markers, microbial translocation and immune activation	28 weeks	In visits at weeks 4, 16 and 28 compared compared to baseline and screening
Proportion of patients with viral rebound	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.	16 weeks	Evaluation on autoimmunity with antithyroid antibodies (antithyroglobulin, antithyroid peroxidase), antinuclear antibodies, antiphospholipid antibodies and rheumatoid factor at screening, baseline and week 16.
Evaluation of the specific immune response thought T-cell proliferation in vitro at screening and baseline	week 0	Proportion of patients with T-cell proliferation in vitro measured by CFSE (carboxyfluorescein succinimidyl ester) at screening and baseline
Changes in the transcriptome of patients visits weeks 4, 16 and 28 compared to baseline (week -12)	28 weeks	Weeks 4, 16 and 28 compared to baseline
Evaluation of the specific immune response thought dendritic cell maturation markers in vitro at screening and baseline	week 0	Proportion of patients with dendritic cell maturation markers in vitro measured by flow cytometry at screening and baseline

Trial Locations

Locations (1)

Hospital Clínic; 🇪🇸 Barcelona, España, Spain