Clinical trial NCT02767193: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infection
Lead sponsor: Fundacion Clinic per a la Recerca Biomédica
Sponsor class: OTHER
First posted: 2016-05-10
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with adverse events of grade 3 or higher
timeFrame: 28 weeks
measure: Virological
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of adverse events grade 1 and 2 within 14 days after each immunization (weeks 2, 4 and 6)
timeFrame: 6 weeks
measure: Changes in the specific immune response
timeFrame: 28 weeks
measure: Changes in levels of viral reservoir.
timeFrame: 28 weeks
measure: Proportion of patients with changes in any value of the levels of inflammatory markers, microbial translocation and immune activation
timeFrame: 28 weeks
measure: Proportion of patients with viral rebound
timeFrame: 15 days
measure: 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.
timeFrame: 16 weeks
measure: Changes in the transcriptome of patients visits weeks 4, 16 and 28 compared to baseline (week -12)
timeFrame: 28 weeks
measure: Evaluation of the specific immune response trought IFN-gamma production in vitro at screening and baseline
timeFrame: week 0
measure: Evaluation of the specific immune response thought dendritic cell maturation markers in vitro at screening and baseline
timeFrame: week 0
measure: Evaluation of the specific immune response thought T-cell proliferation in vitro at screening and baseline
timeFrame: week 0
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic
state: España
Study officials:
References:
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.