This is a descriptive, open-label, multicenter, non-randomized, uncontrolled phase Iclinical study to evaluate the safety, reactogenicity, and immunogenicity of the COVID-19Vaccine (mRNA) - Bio-Manguinhos/Fiocruz at doses of 25 μg, 50 μg, and 100 μg in healthyadults aged 18 to 59 years. Each study cohort (25 μg, 50 μg, and 100 μg) will initiallyinclude a sentinel group of five participants, who will be included sequentially, one byone. This inclusion will allow for an initial integrated risk-benefit assessment,evaluating whether the data from the included participant maintain the risk withinacceptable limits for progression.
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.
Biological: Grupo 1 - dose 25 μg
Administration of the experimental COVID-19 vaccine (mRNA) - Bio-Manguinhos/Fiocruz - at
a dose of 25 μg (single intramuscular dose)
Biological: Group 2 - 50 μg dose
Administration of the experimental COVID-19 vaccine (mRNA) - Bio-Manguinhos/Fiocruz - at
a dose of 50 μg (single intramuscular dose)
Biological: Group 3 - 100 μg
Administration of the experimental COVID-19 vaccine (mRNA) - Bio-Manguinhos/Fiocruz - at
a dose of 100 μg (single intramuscular dose)
Inclusion Criteria:
1. Men and women aged between 18 and 59 years.
2. Negative result for SARS-CoV-2 in a rapid antigen test at screening (Visit 1) and at
the inclusion visit (Visit 0).
3. Body Mass Index >18.9 and <35.0 kg/m².
4. Body weight ≥50.0 kg for men and ≥45.0 kg for women.
5. Complete primary vaccination for COVID-19, and at least one more booster dose, with
the last booster being an mRNA vaccine approved by Anvisa.
6. 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).
7. 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.
8. Ability to understand the study, its objectives, risks, and procedures, and to
provide free and informed consent.
Exclusion Criteria:
1. 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.
2. Administration of another vaccine up to 28 days before or planning to receive
another vaccine within 29 days following the V0 visit.
3. 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).
4. Previous diagnosis of immunodeficiency, autoimmune diseases, or cardiomyopathies.
5. Medium or large surgery performed up to 3 months prior to inclusion.
6. History of malignant neoplasm in the 12 months prior to screening (V-1).
7. Uncontrolled coagulopathy or any hematological condition that contraindicates
intramuscular injection.
8. 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.
9. Use of immunosuppressive medications in the 3 months prior to vaccination.
10. History of antineoplastic chemotherapy treatment.
11. Planning for the use of immunosuppressants or chemotherapeutic agents during the
study period.
12. 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.
13. Use of blood products in the 3 months prior to inclusion.
14. Participation in another clinical study using an investigational product in the 12
months prior to inclusion.
15. Pregnancy or lactation at the time of visit V0, or planning to become pregnant
during the study period.
16. Positive pregnancy test result at screening (visit V1) or on the day of vaccination
(applicable to PEP).
17. 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.
18. 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.
19. 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.
20. Resultado positivo em um ou mais exames de sorologia realizados na triagem.
Not Provided
José Cerbino Neto, Infectious disease physician
+55 (21) 99967-1880
cerbino.neto@fiocruz.br