Dendritic Cell Vaccine to Prevent COVID-19

Adaptive Phase I Clinical Trial of Preventive Vaccine Consisting of Autologous Dendritic Cells Previously Incubated With S-protein From SARS-CoV-2, in Subjects Negative for COVID-19 Infection and Anti-SARS-CoV-2 Antibodies

This is an adaptive Phase I trial of a vaccine consisting of autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein, with or without GM-CSF, to prevent COVID-19 in adults.

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Biological: AV-COVID-19

Detailed Description

Subjects eligible for treatment will be those who at baseline, are not actively infected with SARS-CoV-2, have no evidence of prior infection with SARSCoV- 2 based on serologic testing, and give informed consent for a vaccination with AV-COVID-19. The patient population will include the elderly and others at higher risk for poor outcomes after COVID-19 infection. For this reason, individuals will not be excluded solely on the basis of age, body mass index, history of hypertension, diabetes, cancer, or autoimmune disease.

After enrolling for screening, subjects will undergo a nasal swab test to exclude active COVID-19 infection and a rapid test for anti-coronavirus antibodies to exclude pre-existing anti-SARS-CoV-2 antibodies. 50 mL of blood will be collected, from which peripheral blood monocytes will be isolated and differentiated into DC before incubation with SARS-CoV-2 S-protein, during which time the protein is digested into 9 to 25 amino acid peptide sequences presented on the dendrites of DC in conjunction with histocompatibility class I and class II molecules. Safety and quality testing will be performed on a small quantity of the batch, and the remaining AV-COVID-19 will be cryopreserved for shipping to the treatment site.

Once the Study Drug is ready, if eligible, the subject will be seen at Study Week-0 for treatment. Prior to injection of the Study Drug, a nasal swab test will be collected to confirm that they are still negative for COVID-19, and blood will be drawn to determine baseline levels of anti-SARS-CoV-2 antibodies. At the treatment site, the product will be thawed and admixed with saline or (saline with GM-CSF), and within 5 hours of thawing, will be injected SC via a 25- gauge needle

• Study Type: Interventional
• Enrollment (Anticipated): 27
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Muhammad Karyana, Dr., MPH; Phone Number: +62 21 4261088; Email: mkaryana@gmail.com

Study Locations

• Indonesia
  • Jawa Tengah
    • Semarang, Jawa Tengah, Indonesia, 50244
      • Recruiting
      • Rumah Sakit Umum Pusat Dr. Kariadi
      • Contact: Muchlis Achsan Udji Sofro, MD, Internis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 years or older,
2. in relatively good health with adequate physical and mental function
3. including factors associated with in increased risk for medical complications associated with COVID-19 infection or increased risk for exposure to SARS-CoV-2

Exclusion Criteria:

1. Active COVID-19 infection by PCR testing
2. Pre-existing IgG or IgM SARS-CoV-2 antibodies
3. Pregnant, Known hypersensitivity to GM-CSF
4. Known active immune deficiency disease or active HIV
5. HBV, HCV, On active treatment with corticosteroids or other immunosuppressive agent
6. Participated in previous COVID-19 vaccine study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AV-COVID-19 (0.1 mg antigen, 0 mcg GMCSF); Autologous dendritic cells previously loaded with 0.1 mg SARS-CoV-2 spike protein, admixed with 0 mcg GM-CSF	Biological: AV-COVID-19; Autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein
EXPERIMENTAL: AV-COVID-19 (0.33 mg antigen, 0 mcg GM-CSF); Autologous dendritic cells previously loaded with 0.33 mg SARS-CoV-2 spike protein, admixed with 0 mcg GM-CSF	Biological: AV-COVID-19; Autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein
EXPERIMENTAL: AV-COVID-19 (1.0 mg antigen, 0 mcg GMCSF); Autologous dendritic cells previously loaded with 1.0 mg SARS-CoV-2 spike protein, admixed with 0 mcg GM-CSF	Biological: AV-COVID-19; Autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein
EXPERIMENTAL: Experimental: AV-COVID-19 (0.1 mg antigen, 250 mcg GM-CSF); Autologous dendritic cells previously loaded with 0.1 mg SARS-CoV-2 spike protein, admixed with 250 mcg GM-CSF	Biological: AV-COVID-19; Autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein
EXPERIMENTAL: AV-COVID-19 (0.33 mg antigen, 250 mcg GM-CSF); Autologous dendritic cells previously loaded with 0.33 mg SARS-CoV-2 spike protein, admixed with 250 mcg GM-CSF	Biological: AV-COVID-19; Autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein
EXPERIMENTAL: AV-COVID-19 (1.0 mg antigen, 250 mcg GM-CSF); Autologous dendritic cells previously loaded with 1.0 mg SARS-CoV-2 spike protein, admixed with 250 mcg GM-CSF	Biological: AV-COVID-19; Autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein
EXPERIMENTAL: AV-COVID-19 (0.1 mg antigen, 500 mcg GM-CSF); Autologous dendritic cells previously loaded with 0.1 mg SARS-CoV-2 spike protein, admixed with 500 mcg GM-CSF	Biological: AV-COVID-19; Autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein
EXPERIMENTAL: AV-COVID-19 (0.33 mg antigen, 500 mcg GM-CSF); Autologous dendritic cells previously loaded with 0.33 mg SARS-CoV-2 spike protein, admixed with 500 mcg GM-CSF	Biological: AV-COVID-19; Autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein
EXPERIMENTAL: AV-COVID-19 (1.0 mg antigen, 500 mcg GM-CSF); Autologous dendritic cells previously loaded with 1.0 mg SARS-CoV-2 spike protein, admixed with 500 mcg GM-CSF	Biological: AV-COVID-19; Autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of solicited local and systemic reactogenicity adverse events (AEs)	Percentage of participants with solicited AEs (local, systemic) for 7 days following vaccination by severity score, duration, and peak intensity.	until follow up day 7
Safety Laboratory Values (Serum Chemistry)	Safety laboratory values (Serum Chemistry) by FDA toxicity scoring (absolute and change from baseline where identified) at 7 days after each vaccination.	until follow up day 7
Safety Laboratory Values (Hematology)	Safety laboratory values (Hematology) by FDA toxicity scoring (absolute and change from baseline where identified) at 7 days after each vaccination.	until follow up day 7
Frequency of any serious adverse events (SAEs)	Percentage of participants with serious undesirable effect associated with the use of a medical product in a patient, which consist of death, life-threatening, hospitalization, disability or permanent damage, congenital anomaly/birth defect, required intervention to prevent permanent impairment or damage (devices), dan other serious important medical events	until follow up day 365
Frequency of any new-onset chronic medical conditions (NOCMCs)	NOCMCs will be documented from the time of study vaccination through approximately 1 year after study vaccination	until follow up day 365
Frequency of medically attended adverse events (MAAEs)	Percentage of participants with MAAEs, defined as AEs that lead to an unscheduled visit to a healthcare practitioner, through Day 365 by MedDRA classification, severity score, and relatedness.	until follow up day 365
Frequency of Unsolicited AE and Adverse Events of Special Interest (AESIs)	Percentage of participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, all MAAEs) or AESIs (potential immune-mediated medical conditions or AEs relevant to COVID-19) through the first 90 days by MedDRA classification, severity score, and relatedness.	until follow up day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs)	Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs through Day 28.	until follow up day 28
Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs)	Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by enzyme-linked immunosorbent assay (ELISA) expressed as GMTs through Day 28.	until follow up day 28
Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs)	Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs through Day 28. SCR is the proportion of participants with ≥4-fold rises in ELISA units.	until follow up day 28
Neutralizing Antibody Activity Expressed as GMTs	Neutralizing antibody activity as detected by microneutralization assay (MN) expressed as GMTs at multiple time points through Day 28.	until follow up day 28
Neutralizing Antibody Activity Expressed as GMFRs	Neutralizing antibody activity as detected by MN expressed as GMFRs at multiple time points through Day 28.	until follow up day 28
Neutralizing Antibody Activity Expressed as SCRs	Neutralizing antibody activity as detected by MN expressed as SCRs at multiple time points through Day 28.	until follow up day 28
Assessment of Cell-Mediated (T helper 1 [Th1]/T helper 2 [Th2]) Pathways	Cell-mediated (Th1/Th2) pathways as measured by whole blood (flow cytometry) and/or in vitro peripheral blood mononuclear cell (PBMC) stimulation (eg, enzyme-linked immunospot [ELISpot], cytokine staining) with SARS-CoV-2 rS protein(s) through Day 28.	until follow up day 28
Optimal dose of SARS-CoV2 antigen and GM-CSF	Measurement of IgG in subject blood after one month	until follow up month one
Duration of detection IgG and neutralizing antibody againts SARS-CoV-2in blood after vaccination	Measurement of IgG and neutralizing antibody in subject blood after 12 months	until follow up month 12

Collaborators and Investigators

• Sponsor: Indonesia-MoH
• Collaborators: National Institute of Health Research and Development, Ministry of Health Republic of Indonesia; Aivita Biomedical, Inc.; PT AIVITA Biomedika Indonesia; RSUP Dr. Kariadi Semarang, indonesia; Faculty of Medicine University of Diponegoro, Indonesia
• Investigators: Principal Investigator: Djoko Wibisono, Dr. Internis, Rumah Sakit Pusat Angkatan Darat (RSPAD) Gatot Soebroto, Jakarta; Principal Investigator: Muhammad Karyana, National Institute of Health Research and Development

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 7, 2020
• Primary Completion (ANTICIPATED): January 31, 2021
• Study Completion (ANTICIPATED): January 31, 2022

Study Registration Dates

• First Submitted: December 22, 2020
• First Submitted That Met QC Criteria: December 24, 2020
• First Posted (ACTUAL): December 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 24, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: vaccine; covid-19; dendritic cell
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: CL-COV-P02-ID; U1111-1263-0568 (OTHER: WHO-UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No