Dendritic Cell Vaccine to Prevent COVID-19

• ClinicalTrials.gov Identifier: NCT04685603
• Recruitment Status: Unknown
• First Posted: December 28, 2020
• Last Update Posted: December 29, 2020
• Sponsor: Indonesia-MoH
• Collaborators: Aivita Biomedical, Inc.; PT AIVITA Biomedika Indonesia; National Institute of Health Research and Development, Ministry of Health Republic of Indonesia; RSUP Dr. Kariadi Semarang, indonesia; Faculty of Medicine University of Diponegoro, Indonesia
• Information provided by (Responsible Party): Indonesia-MoH

Tracking Information

• First Submitted Date: December 22, 2020
• First Posted Date: December 28, 2020
• Last Update Posted Date: December 29, 2020
• Actual Study Start Date: December 7, 2020
• Estimated Primary Completion Date: January 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 24, 2020)

• Frequency of solicited local and systemic reactogenicity adverse events (AEs) [ Time Frame: until follow up day 7 ]
  Percentage of participants with solicited AEs (local, systemic) for 7 days following vaccination by severity score, duration, and peak intensity.
• Safety Laboratory Values (Serum Chemistry) [ Time Frame: until follow up day 7 ]
  Safety laboratory values (Serum Chemistry) by FDA toxicity scoring (absolute and change from baseline where identified) at 7 days after each vaccination.
• Safety Laboratory Values (Hematology) [ Time Frame: until follow up day 7 ]
  Safety laboratory values (Hematology) by FDA toxicity scoring (absolute and change from baseline where identified) at 7 days after each vaccination.
• Frequency of any serious adverse events (SAEs) [ Time Frame: until follow up day 365 ]
  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
• Frequency of any new-onset chronic medical conditions (NOCMCs) [ Time Frame: until follow up day 365 ]
  NOCMCs will be documented from the time of study vaccination through approximately 1 year after study vaccination
• Frequency of medically attended adverse events (MAAEs) [ Time Frame: until follow up day 365 ]
  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.
• Frequency of Unsolicited AE and Adverse Events of Special Interest (AESIs) [ Time Frame: until follow up day 90 ]
  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.

Original Primary Outcome Measures (submitted: December 24, 2020)

• Frequency of solicited local and systemic reactogenicity adverse events (AEs) [ Time Frame: until follow up day 7 ]
  Percentage of participants with solicited AEs (local, systemic) for 7 days following vaccination by severity score, duration, and peak intensity.
• Safety Laboratory Values (Serum Chemistry, Hematology) [ Time Frame: until follow up day 28 ]
  Safety laboratory values (serum chemistry, hematology) by FDA toxicity scoring (absolute and change from baseline where identified) at 7 days after each vaccination.
• Frequency of any serious adverse events (SAEs) [ Time Frame: until follow up day 365 ]
  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
• Frequency of any new-onset chronic medical conditions (NOCMCs) [ Time Frame: until follow up day 365 ]
  NOCMCs will be documented from the time of study vaccination through approximately 1 year after study vaccination
• Frequency of medically attended adverse events (MAAEs) [ Time Frame: until follow up day 365 ]
  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.
• Frequency of Unsolicited AE and Adverse Events of Special Interest (AESIs) [ Time Frame: until follow up day 90 ]
  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.

• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: December 24, 2020)

• Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs) [ Time Frame: until follow up day 28 ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs through Day 28.
• Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs) [ Time Frame: until follow up day 28 ]
  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.
• Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs) [ Time Frame: until follow up day 28 ]
  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.
• Neutralizing Antibody Activity Expressed as GMTs [ Time Frame: until follow up day 28 ]
  Neutralizing antibody activity as detected by microneutralization assay (MN) expressed as GMTs at multiple time points through Day 28.
• Neutralizing Antibody Activity Expressed as GMFRs [ Time Frame: until follow up day 28 ]
  Neutralizing antibody activity as detected by MN expressed as GMFRs at multiple time points through Day 28.
• Neutralizing Antibody Activity Expressed as SCRs [ Time Frame: until follow up day 28 ]
  Neutralizing antibody activity as detected by MN expressed as SCRs at multiple time points through Day 28.
• Assessment of Cell-Mediated (T helper 1 [Th1]/T helper 2 [Th2]) Pathways [ Time Frame: until follow up day 28 ]
  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.
• Optimal dose of SARS-CoV2 antigen and GM-CSF [ Time Frame: until follow up month one ]
  Measurement of IgG in subject blood after one month
• Duration of detection IgG and neutralizing antibody againts SARS-CoV-2in blood after vaccination [ Time Frame: until follow up month 12 ]
  Measurement of IgG and neutralizing antibody in subject blood after 12 months

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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

• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein

Masking: Double (Participant, Investigator)
Primary Purpose: Prevention

• Condition: COVID-19

Intervention

Biological: AV-COVID-19

Autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein

Study Arms

• 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
  Intervention: Biological: AV-COVID-19
• 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
  Intervention: Biological: AV-COVID-19
• 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
  Intervention: Biological: AV-COVID-19
• 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
  Intervention: Biological: AV-COVID-19
• 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
  Intervention: Biological: AV-COVID-19
• 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
  Intervention: Biological: AV-COVID-19
• 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
  Intervention: Biological: AV-COVID-19
• 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
  Intervention: Biological: AV-COVID-19
• 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
  Intervention: Biological: AV-COVID-19

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 24, 2020): 27
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 31, 2022
• Estimated Primary Completion Date: January 31, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Indonesia

Administrative Information

• NCT Number: NCT04685603
• Other Study ID Numbers: CL-COV-P02-ID; U1111-1263-0568 ( Other Identifier: WHO-UTN )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Indonesia-MoH
• Original Responsible Party: Same as current
• Current Study Sponsor: Indonesia-MoH
• Original Study Sponsor: Same as current

Collaborators

• Aivita Biomedical, Inc.
• PT AIVITA Biomedika Indonesia
• National Institute of Health Research and Development, Ministry of Health Republic of 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

• PRS Account: Indonesia-MoH
• Verification Date: December 2020