Bio-Manguinhos/Fiocruz COVID-19 (mRNA) Vaccine Booster

The inclusion of cohorts, defined by dose, will be carried out in a staggered manner in the following order:

Sentinel group 1 (25 μg dose): Analysis of reactogenicity and safety data from 5 participants, who will be included one at a time and evaluated 48 hours after administration of the investigational product. The safety data from these participants will be obtained 7 days after vaccination and evaluated by the CMDS to allow the inclusion of the remaining 25 participants from this dose, as well as the participants from the sentinel group of the 50 μg dose.

Sentinel group 2 (50 μg dose): Analysis of reactogenicity and safety data from 5 participants, who will be included one at a time and evaluated 48 hours after administration of the investigational product. Safety data from these participants will be obtained 7 days after vaccination and evaluated by the CMDS to allow the inclusion of the remaining 25 participants from this dose, as well as the participants from the sentinel group of the 100 μg dose.

Sentinel Group 3 (100 μg dose): Analysis of reactogenicity and safety data from 5 participants, who will be included one at a time and evaluated 48 hours after administration of the investigational product. Safety data from these participants will be obtained 7 days after vaccination and evaluated by the CMDS to allow the inclusion of the remaining 25 participants in this dose.

At the end of this period, a formal cumulative safety review will be conducted by the Data and Safety Monitoring Committee (CMDS), which will evaluate all available safety data from the sentinel group, including: solicited and unsolicited adverse events; serious adverse events; severe adverse events; vital signs; laboratory data; and any other relevant clinical findings. The CMDS will issue a documented report recommending or not the continuation of the study.

The study population will consist of 90 adult participants who received complete primary vaccination for COVID-19, and at least one additional booster dose, the last booster being an mRNA vaccine approved by ANVISA, administered at least 6 months prior to inclusion.

The study design was based on the European Medicines Agency - EMA guideline, ANVISA-RDC 945/2024 and Law 14.874/2024 [4] and other phase I clinical studies of RNA-based vaccines for COVID-19.

Data from this study will support decisions on whether the candidate vaccine should be further evaluated in advanced phase clinical trials, guide dose selection, and support platform development. If the monovalent candidate induces potentially protective immune responses with an acceptable safety profile, there may be potential to develop future multivalent vaccines to prevent COVID-19 disease based on this platform.

The clinical study will begin immediately after ethical and regulatory approvals. The participant inclusion period is estimated to be 6 months. Follow-up of each participant will require another 6 months. Therefore, the total time required between the first visit of the first participant included and the last visit of the last participant is approximately 12 months.

Description of the Experimental Intervention: The COVID-19 Vaccine (mRNA) - Bio-Manguinhos/Fiocruz is a monovalent vaccine for the prevention of severe cases of COVID-19. The product under investigation consists of a formulation containing messenger ribonucleic acid (mRNA) encoding the Spike protein of the XBB variant of the SARS-CoV-2 virus.

Randomization: There will be no randomization in this study. Blinding/Breaking of Blinding: The study is open-label. There will be no blinding.

Inclusion criteria

• Men and women aged between 18 and 59 years.
• Negative result for SARS-CoV-2 in a rapid antigen test at screening (Visit 1) and at the inclusion visit (Visit 0).
• Body Mass Index >18.9 and <35.0 kg/m².
• Body weight ≥50.0 kg for men and ≥45.0 kg for women.
• Complete primary vaccination for COVID-19, and at least one more booster dose, with the last booster being an mRNA vaccine approved by Anvisa.
• At least one booster dose with an mRNA-based vaccine, with the last booster given at least 6 months prior to the enrollment date (proven by a vaccination certificate or registration in the SI-PNI system).
• Participants with the potential to become pregnant (PPE), as well as men with PPE partners, must agree to use effective contraceptive methods throughout the study participation period.
• Ability to understand the study, its objectives, risks, and procedures, and to provide free and informed consent.

Exclusion criteria

• Presence of any active infection at the time of vaccination or fever up to 7 days before the V0 visit. Participants in this condition may be rescheduled.
• Administration of another vaccine up to 28 days before or planning to receive another vaccine within 29 days following the V0 visit.
• Absolute or relative contraindications to the mRNA-based COVID-19 vaccine:

• Confirmed prior anaphylaxis to mRNA vaccines or any of their components, especially polyethylene glycol (PEG).
• History of anaphylaxis to other vaccines or injectable medications.
• History of myocarditis or pericarditis prior to vaccination.
• History of multisystem inflammatory syndrome (MIS-C or MIS-A).
• Previous diagnosis of immunodeficiency, autoimmune diseases, or cardiomyopathies.
• Medium or large surgery performed up to 3 months prior to inclusion.
• History of malignant neoplasm in the 12 months prior to screening (V-1).
• Uncontrolled coagulopathy or any hematological condition that contraindicates intramuscular injection.
• Presence of decompensated or uncontrolled chronic disease at the time of inclusion. At the investigator's discretion, participants with stable chronic disease may be included.
• Use of immunosuppressive medications in the 3 months prior to vaccination.
• History of antineoplastic chemotherapy treatment.
• Planning for the use of immunosuppressants or chemotherapeutic agents during the study period.
• Current use of corticosteroids at immunosuppressive doses. Immunosuppressive doses are considered to be ≥10 mg/day of prednisone (or equivalent) systemically for 14 days or more.
• Use of blood products in the 3 months prior to inclusion.
• Participation in another clinical study using an investigational product in the 12 months prior to inclusion.
• Pregnancy or lactation at the time of visit V0, or planning to become pregnant during the study period.
• Positive pregnancy test result at screening (visit V1) or on the day of vaccination (applicable to PEP).
• Presence of tattoos, scars, discoloration, or any skin alteration at the application site that, in the investigator's opinion, may interfere with the assessment of local reactogenicity.
• Any medical, psychological, or social condition that, in the investigator's opinion, may compromise the participant's safety, adherence to the protocol, or the integrity of the data.
• Clinically significant changes in screening laboratory tests (visit V1):

• Hemoglobin ≤ 10.9 g/dL;
• White blood cells < 2,500 cells/mm³;
• Absolute neutrophils < 1,000 cells/mm³;
• ESR above the upper limit of normal (ULN) >20 mm/h for men >30 mm/h for women;
• ALT, AST, GGT or ALP >1.25 × ULN;
• Total bilirubin >1.1 × ULN;
• Urea >1.1 × ULN;
• Creatinine >1.1 × ULN;
• Glycated hemoglobin >5.6%;
• Troponin I >1.1 × ULN;
• PT or aPTT >1.1 × ULN; • CPK above the ULN (men: >174 U/L; women: >140 U/L);
• C-reactive protein >1.0 mg/dL.
• Resultado positivo em um ou mais exames de sorologia realizados na triagem.