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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Biological: DCV3; Biological: DCV3 with PEG-INF; Biological: Placebo; Biological: Placebo with PEG-INF

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • España
    • Barcelona, España, Spain, 08036
      • Hospital Clínic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DCV3; Autologus differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus	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
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	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
Placebo Comparator: CD placebo; Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded	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
Placebo Comparator: CD placebo + PEG-INF; Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded with PEG-INF	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	28 weeks
Virological	Proportion of patients with undetectable viral load (<37 copies / mL) at 12 weeks	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	28 weeks
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.	28 weeks
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	28 weeks
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.	15 days
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.	16 weeks
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	28 weeks
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	week 0
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	week 0
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	week 0

Collaborators and Investigators

• Sponsor: Judit Pich Martínez

Publications and helpful links

General Publications

• Leal L, Couto E, Sánchez-Palomino S, Climent N, Fernández I, Miralles L, Romero Y, González T, Maleno MJ, Paño B, Pich J, Nicolau C, Gatell JM, Plana M, García F; DCV3-RISVAC04 Study Group. Effect of Intranodally Administered Dendritic Cell-Based HIV Vaccine in Combination With Pegylated Interferon α-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.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): May 22, 2019
• Study Completion (Actual): May 22, 2019

Study Registration Dates

• First Submitted: April 22, 2016
• First Submitted That Met QC Criteria: May 6, 2016
• First Posted (Estimate): May 10, 2016

Study Record Updates

• Last Update Posted (Actual): July 26, 2019
• Last Update Submitted That Met QC Criteria: July 25, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: DCV3/RisVac04; 2015-001795-22 (EudraCT Number)