A phase I study to evaluate safety and immunogenicity of recombinant protein candidate vaccine against SARS-CoV-2 in healthy volunteers

INTERVENTION: Product Name: PHH‐1V Pharmaceutical Form: Emulsion for injection INN or Proposed INN: PHH‐1V Other descriptive name: PHH‐1V Concentration unit: µg microgram(s) Concentration type: range Concentration number: 10‐40 Trade Name: Comirnaty Pharmaceutical Form: Dispersion for injection INN or Proposed INN: BNT162b2SA Other descriptive name: BNT162b2SA Concentration unit: ml millilitre(s) Concentration type: equal Concentration number: 0.3‐ CONDITION: SARS‐CoV‐2 ; MedDRA version: 23.0 Level: LLT Classification code 10084272 Term: SARS‐CoV‐2 infection System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: To assess safety and tolerability of COVID‐19 HIPRA vaccine in healthy adult volunteers. Safety will be measured by solicited and unsolicited reactions (local and systemic) following each dose vaccination. Primary end point(s): 1.1 Number and percentage of solicited local and systemic reactogenicity adverse events for 7 days following each vaccination.; 1.2 Number and percentage of unsolicited local and systemic reactogenicity adverse events for 28 days following each vaccination.; Local solicited reactions will be collected as pain, tenderness, erythema/redness, and induration/swelling.; Systemic solicited events will be collected as fever, nausea/vomiting, diarrhoea, headache, fatigue and myalgia Secondary Objective: 1.Overall safety of COVID‐19 HIPRA vaccine.; 2.Immunogenicity measured by wild‐type and pseudovirus neutralization at baseline and 3‐weeks after the first dose and 2‐weeks after the second dose of vaccine.; 3.Immunogenicity measured by wild‐type and pseudovirus neutralization at long‐term, i.e. 24 and 48 weeks after the second dose of vaccine.; 4.Immunogenicity measured by enzyme‐linked immunosorbent assay (ELISA) to the SARS‐CoV‐2 spike glycoprotein at baseline and 3‐weeks after the first dose and 2‐weeks after the second dose of vaccine.; 5.Immunogenicity measured by enzyme‐linked immunosorbent assay (ELISA) to the SARS‐CoV‐2 spike glycoprotein at long‐term, i.e. 24 and 48 weeks after the second dose of vaccine.; 6.T‐cell mediated responses against the SARS‐CoV‐2 S glycoprotein at baseline and 2‐weeks after the second dose of vaccine.; 7.Th‐1/Th‐2 T‐cell mediated responses against the SARS‐CoV‐2 S glycoprotein at baseline and 2‐weeks after the second dose of vaccine. Timepoint(s) of evaluation of this end point: 7 and 28 days SECONDARY OUTCOME: Secondary end point(s): 1.1 Change from baseline in safety laboratory parameters at 7 days following each vaccination.; 1.2 Number and percentage of serious adverse events throughout the study duration.; 1.3 Number and percentage of adverse events of special interest (AESI) throughout the study duration.; 1.4 Number and percentage of medically attended adverse events (MAAE) related to study vaccine throughout the study duration.; 2.1 Neutralization titer measured as Inhibitory concentration 50 (IC50) for each individual sample and geometric mean titer (GMT) for group comparison at Day 21 and 35. IC50 measured by a quantitative PRNT (plaque reduction neutralization test) and PBNA (pseudovirion‐based neutralization assay).; 2.2 Geometric mean fold rise (GMFR) in neutralizing antibodies titers from baseline at Day 21 and 35.; 3.1 Neutralization titer measured as IC50 for each individual sample and GMT for group comparison at 24 and 48 weeks after the second dose.; IC50 measured by a quantitative PRNT (plaque reduction neutralization test) and PBNA (pseudovirion‐based neutralization assay).; 3.2 GMFR in neutralizing antibodies titers from baseline at 24 and 48 weeks after the second dose.; 4.1 Binding antibody IgG titer measured for each individual sample and GMT for group comparison at Day 21 and 35.; 4.2 GMFR in IgG titer from baseline at Day 21 and 35.; 5.1 Binding antibody IgG titer measured for each individual sample and GMT for group comparison at 24 and 48 weeks after the second dose.; 5.2 GMFR in IgG titer from baseline at 24 and 48 weeks after the second dose.; 6.1 T‐cell‐mediated response to the SARS‐CoV‐2 S protein as measured by whole PBMC stimulation by ELISpot at baseline and at Day 35.; 7.1 CD4+/CD8+ T‐cell response to the SARS‐CoV‐2 S protein as measured by in vitro PBMC stimulation by cytokine staining assays at baseline and at Day 35. Timepoint(s) of evaluation of this end point: Days 21, 28 and 35.; 24 and 48 weeks after the second dose. INCLUSION CRITERIA: 1. Adults males or females between 18‐39 years of age at the day of screening. 2. Willing and able to comply with scheduled visits, laboratory test, complete diaries and other study procedures. 3. Body Mass Index 18 to 40 Kg/m2 at screening. 4. COVID19 negative PCR test and negative serum IgG binding antibody response to the SARS‐CoV‐2 S glycoprotein at screening or prior the first vaccination. 5. Willing to avoid all other vaccines within 4 weeks before and after each injection. Seasonal influenza vaccination is allowed if it is received at least 14 days before or after the vaccination. 6. Women of childbearing potential must have a negative pregnancy test in urine before the inclusion of the study and prior to each vaccination. 7. If female of childbearing potential, willing to use highly effective contraceptive methods or have practiced sexual abstinence from the screening visit until 8 weeks after the last injection. Highly effective contra