Clinical trial NCT04685603: Dendritic Cell Vaccine to Prevent COVID-19
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: COVID-19
Keywords: covid-19
vaccine
dendritic cell
Lead sponsor: Indonesia-MoH
Sponsor class: OTHER_GOV
Collaborators: name: Aivita Biomedical, Inc.
name: PT AIVITA Biomedika Indonesia
name: National Institute of Health Research and Development, Ministry of Health Republic of Indonesia
name: RSUP Dr. Kariadi Semarang, indonesia
name: Faculty of Medicine University of Diponegoro, Indonesia
First posted: 2020-12-28
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein
Primary purpose: PREVENTION

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Frequency of solicited local and systemic reactogenicity adverse events (AEs)
timeFrame: until follow up day 7
measure: Safety Laboratory Values (Serum Chemistry)
timeFrame: until follow up day 7
measure: Safety Laboratory Values (Hematology)
timeFrame: until follow up day 7
measure: Frequency of any serious adverse events (SAEs)
timeFrame: until follow up day 365
measure: Frequency of any new-onset chronic medical conditions (NOCMCs)
timeFrame: until follow up day 365
measure: Frequency of medically attended adverse events (MAAEs)
timeFrame: until follow up day 365
measure: Frequency of Unsolicited AE and Adverse Events of Special Interest (AESIs)
timeFrame: until follow up day 90
Secondary outcomes:
measure: Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs)
timeFrame: until follow up day 28
measure: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs)
timeFrame: until follow up day 28
measure: Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs)
timeFrame: until follow up day 28
measure: Neutralizing Antibody Activity Expressed as GMTs
timeFrame: until follow up day 28
measure: Neutralizing Antibody Activity Expressed as GMFRs
timeFrame: until follow up day 28
measure: Neutralizing Antibody Activity Expressed as SCRs
timeFrame: until follow up day 28
measure: Assessment of Cell-Mediated (T helper 1 [Th1]/T helper 2 [Th2]) Pathways
timeFrame: until follow up day 28
measure: Optimal dose of SARS-CoV2 antigen and GM-CSF
timeFrame: until follow up month one
measure: Duration of detection IgG and neutralizing antibody againts SARS-CoV-2in blood after vaccination
timeFrame: until follow up month 12
Other outcomes:
Locations:
city: Semarang
country: Indonesia
facility: Rumah Sakit Umum Pusat Dr. Kariadi
state: Jawa Tengah
Study officials:
affiliation: Rumah Sakit Pusat Angkatan Darat (RSPAD) Gatot Soebroto, Jakarta
name: Djoko Wibisono, Dr. Internis
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute of Health Research and Development
name: Muhammad Karyana
role: PRINCIPAL_INVESTIGATOR
References: