CompletedNCT05354024ButanvacUpdated Feb 6, 2025

Phase II/III Randomized Clinical Trial of Booster Dose of COVID-19 (Recombinant, Inactivated) Vaccine

A Phase 2/3 interventional study of NDV-HXP-S 10μg and BNT162b2 30μg in Coronavirus Infections and Healthy, sponsored by Butantan Institute. Completed at 6 sites in Brazil. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-02-06.

Sponsored by Butantan Institute · Phase 2/3, Interventional, and Prevention

Phase: Phase 2/3
Study type: Interventional
Enrollment: 4,400
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

NDV-HXP-S is an inactivated COVID-19 vectored-vaccine virus using the Newcastle Disease Virus as basis and expressing Spike (S) protein from SARS-CoV-2 stabilized in pre-fusion form with Hexapro technology.

This vaccine was successfully tested in non-clinical and clinical studies with a good safety profile and eliciting neutralizing antibodies against SARS-CoV-2. Clinical testing is conducted by an international consortium including three different manufacturers. Butantan, in Brazil, is one of them.

Read the detailed description

The present protocol of Phase II/III studies.The Phase II study consists in a randomized (1:1) controlled double-blinded trial that aims to evaluate the safety and immunogenicity of NDV-HXP-S 10μg as a dose of booster in comparison to the vaccine against COVID-19 BNT162b2 30μg in a population of 400 adult subjects (50% with age ≥ 60 years), regardless of past of infection by COVID-19, with proof of two or more doses of COVID-19, of which the last dose administered at least 120 days ago.

The Phase III study consists in a randomized (3:1) controlled double-blinded trial that aims to evaluate the safety, immunogenicity and consistency of three consecutive batches of NDV-HXP-S 10μg as a dose of booster in comparison to the vaccine against COVID-19 BNT162b2 30μg in a population of 4000 adult subjects (20% with age ≥ 60 years), with similar characteristics as the population of Phase II.

Conditions studied

Coronavirus Infections
Healthy

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Keywords

Vaccine
SARS-CoV-2
COVID-19

In context

COVID-19

7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.

This study's enrollment of 4,400 is above the median of 100 across 4,099 interventional studies indexed under COVID-19.

Browse COVID-19 studies →

Lead sponsor

Butantan Institute is the lead sponsor of 30 studies on the registry; 4 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

Age ≥ 18 years, of which 50% and 20% were aged ≥60 years in Phase II and Phase III studies, respectively, regardless of previous SARS-CoV-2 infection status, with proof of four doses of any monovalent vaccine against COVID-19, of which the last dose administered at least 120 days to 540 days ago.
If pre-existing medical conditions: be in a stable condition that does not require hospitalization or significant changes in therapy during the three months prior to enrollment.
Agree to regular contact by phone, electronic means, and/or home visits.
Intention to participate in the study, documented by the Informed Consent Form.

Exclusion criteria

Exclusion Criteria:

Administration of a vaccine of active or inactivated virus not provided for in the study regimen up to 30 days before the dose of the study vaccine.
Use of other COVID-19 vaccination regimen other than the one contemplated in item a. of the inclusion criteria.
Angioedema or anaphylactic reaction to previous immunizations.
Allergy to egg or chicken.
Severe allergic reaction or anaphylaxis to the vaccine or components of the study vaccine.
Suspected or confirmed fever within 24 hours prior to vaccination or an axillary temperature greater than 37.8°C* on the day of vaccination (inclusion may be delayed until the subject is fever-free for 24 hours), as well as confirmation of SARS-CoV-2 infection (enrollment should be deferred until the participant has completed 24 hours without fever or until the participant resolves the SARS-CoV-2 infection documented by two negative RT-PCR tests).
Evidence of uncontrolled active neurological, cardiac, pulmonary, liver or kidney disease. Significant treatment changes or hospitalizations for worsening the condition in the last three months are indicators of uncontrolled disease.
Bleeding disorders (e.g., clotting factor deficiency, coagulopathy, platelet dysfunction), or previous history of significant bleeding or bruising after intramuscular injection or venipuncture.
Neoplastic diseases (except basal cell carcinoma and cervical carcinoma in situ) diagnosed or under investigation.
Suspected or confirmed immune compromising diseases including congenital or acquired immunodeficiencies and autoimmune diseases not under control according to the medical history or physical examination, including asplenia. Significant treatment changes or hospitalizations for worsening the condition in the last three months are indicators of uncontrolled disease.
Use of immunosuppressive therapies six months prior to study inclusion or scheduled to be of service within two years of inclusion. The dose of corticosteroid considered immunosuppressive is the equivalent of prednisone at a dose of 20 mg/day for adults for more than 14 days. Continued use of topical or nasal corticosteroids and other topical immunomodulators or immunosuppressants will not be considered immunosuppressive. The following are considered immunosuppressive therapies: antineoplastic chemotherapy, radiotherapy, immunosuppressants to induce transplant tolerance, immunosuppressive and immunobiological treatments in patients with autoimmune rheumatic diseases, among others.
Use of blood products (transfusions or immunoglobulins) within the last three months prior to study inclusion or scheduled blood product or immunoglobulin administration within six months of study inclusion.
Alcohol or drug abuse in the past 12 months prior to the subject's inclusion.
Behavioral, cognitive, or psychiatric illness that affects the subject's ability to understand and cooperate with the study protocol requirements.
Being team member conducting the study or having a dependent relationship with one of the study team members.
Any other condition that may jeopardize the safety or rights of a potential participant or prevent him/her from complying with this protocol.
Abnormalities in screening laboratory tests are considered to be excludable in the opinion of the principal investigator or his/her medical representative. If any changes in the tests are considered temporary, the tests may be repeated up to three times during the screening period (Phase II only)
Positive serology tests for human immunodeficiency virus (anti-HIV1/2 ELISA); Hepatitis B (HbsAg or Anti-HBc) or Hepatitis C (total Anti-HCV ELISA).
Any other findings that the investigator expect to would increase the risk of adverse outcomes from study participation.
For women of childbearing potential:
Pregnancy (confirmed by positive β-hCG test), being a breastfeeding, and/or manifest intention to have sexual practices with reproductive potential without the use of a contraceptive method (abstinence, sterilization, intrauterine or implantable contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive gel, cream, or foam) within 30 days before and 28 days after vaccination.
- Note: * The temperature measured with a temporal scanner skin thermometer is considered equivalent to the axillary temperature.

Study design

Phase: Phase 2 / Phase 3
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Care provider, Investigator)
Enrollment: 4,400 participants (actual)

Study arms

Experimental
NDV-HXP-S 10μg (Phase II)
In the Phase III, 200 adult subjects will be assigned to receive NDV-HXP-S 10μg/0.5mL intramuscular (deltoid), booster, 1 dose. All the population will be evaluated for safety and immunogenicity.
Biological: NDV-HXP-S 10μg
Active comparator
BNT162b2 30μg (Phase II)
In the Phase III, 200 adult subjects will be assigned to receive vaccine against COVID-19 BNT162b2 30μg/0.3mL intramuscular (deltoid), booster, 1 dose. All the population will be evaluated for safety and immunogenicity.
Biological: BNT162b2 30μg
Experimental
NDV-HXP-S 10μg batch 1 (Phase III)
In the Phase III, 1000 adult subjects will be assigned to receive the first consecutive batch of NDV-HXP-S 10μg/0.5mL intramuscular (deltoid), booster, 1 dose. All the population will be evaluated for safety. Of them, 250 will be evaluated for immunogenicity and consistency of batches.
Biological: NDV-HXP-S 10μg
Experimental
NDV-HXP-S 10μg batch 2 (Phase III)
In the Phase III, 1000 adult subjects will be assigned to receive the second consecutive batch of NDV-HXP-S 10μg/0.5mL intramuscular (deltoid), booster, 1 dose. All the population will be evaluated for safety. Of them, 250 will be evaluated for immunogenicity and consistency of batches.
Biological: NDV-HXP-S 10μg
Experimental
NDV-HXP-S 10μg batch 3 (Phase III)
In the Phase III, 1000 adult subjects will be assigned to receive the third consecutive batch of NDV-HXP-S 10μg/0.5mL intramuscular (deltoid), booster, 1 dose. All the population will be evaluated for safety. Of them, 250 will be evaluated for immunogenicity and consistency of batches.
Biological: NDV-HXP-S 10μg
Active comparator
BNT162b2 30μg (Phase III)
In the Phase III, 1000 adult subjects will be assigned to receive the vaccine against COVID-19 BNT162b2 30μg/0.3mL intramuscular (deltoid), booster, 1 dose. All the population will be evaluated for safety. Of them, 250 will be evaluated for immunogenicity only.
Biological: BNT162b2 30μg

Interventions

BiologicalNDV-HXP-S 10μg
NDV-HXP-S 10μg/0.5mL intramuscular (deltoid), 1 dose (booster)
BiologicalBNT162b2 30μg
Vaccine against COVID-19 BNT162b2 30μg/0.3mL intramuscular (deltoid), 1 dose (booster)

What researchers measure

Primary outcomes

Solicited and unsolicited adverse reactions
Frequency and intensity of local and systemic solicited and unsolicited adverse reactions.
Time frame: Within to 7 days after vaccination booster dose
Unsolicited adverse reactions
Frequency and intensity of all unsolicited grade ≥2 adverse reactions.
Time frame: Within 28 days after vaccination booster dose
Severe adverse events
Frequency, intensity and relatedness of severe adverse events.
Time frame: Within 28 days after vaccination booster dose
Neutralization GMTR SARS-CoV-2 pseudovirus
Neutralization of Geometric mean titer ratio (GMTR) SARS-CoV-2 pseudovirus.
Time frame: Up to 28 days after vaccination booster dose
Seroconversion Neutralization GMT SARS-CoV-2 pseudovirus
Percentage of subjects with Seroconversion Neutralization GMT SARS-CoV-2 pseudovirus.
Time frame: Up to 28 days after vaccination booster dose

Secondary outcomes

GMT SARS-CoV-2 pseudovirus
Neutralization of Geometric mean titer (GMT) SARS-CoV-2 pseudovirus.
Time frame: Up to 28 days after vaccination booster dose
Neutralization GMFR SARS-CoV-2 pseudovirus
Neutralization Geometric mean fold rise ratio (GMFR) SARS-CoV-2 pseudovirus.
Time frame: Up to 28 days after vaccination booster dose
GMTR against SARS-CoV-2 (ELISA)
Geometric mean titer ratio (GMTR) of Anti-SARS-CoV-2-S IgG antibodies (ELISA).
Time frame: Up to 28 days after vaccination booster dose
Seroconversion anti-SARS-CoV-2 ELISA
Percentage of subjects with seroconversion of Anti-SARS-CoV-2 S IgG antibodies (ELISA).
Time frame: Up to 28 days after vaccination booster dose
GMFR against SARS-CoV-2 (ELISA)
Geometric mean fold rise ratio (GMFR) of Anti-SARS-CoV-2-S IgG titers (ELISA).
Time frame: Up to 28 days after vaccination booster dose
GMT against SARS-CoV-2 (ELISA)
Geometric mean titer (GMT) of Anti-SARS-CoV-2-S IgG antibodies (ELISA).
Time frame: Up to 28 days after vaccination booster dose
GMT against SARS-CoV-2 (ELISA)
Geometric mean titer (GMT) of Anti-SARS-CoV-2-S IgG antibodies (ELISA).
Time frame: Up to 3 and 12 months after vaccine booster dose
Neutralization GMT against SARS-CoV-2 pseudovirus (variants of concern)
Neutralization of Geometric mean titer (GMT) against SARS-CoV-2 pseudovirus (variants of concern)
Time frame: Up to 28 days after vaccination booster dose
T cell-mediated response against SARS-CoV-2
Vaccine-induced T cell immune response against SARS-CoV-2 (parental and variants of concern) by AIM (Activation-Induced Marker) and electrochemiluminescence Meso Scale Discovery® (MSD) V-PLEX Human Biomarker.
Time frame: Up to 12 months after vaccine booster dose
Serious adverse events
Frequency, intensity and relatedness of serious adverse events.
Time frame: Up to 12 months after vaccine booster dose
Adverse events of special interest
Frequency, intensity and relatedness of adverse events of special interest.
Time frame: Up to 12 months after vaccine booster dose
Unsolicited adverse events
Frequency and intensity of all unsolicited adverse events.
Time frame: Up to12 months after vaccine booster dose
Hematologic and biochemical assessments (Phase II)
Frequency, severity and relatedness of hematologic (hemoglobin, white blood cells and platelets) and biochemical (AST, ALT, bilirubins and creatinine) out of reference values.
Time frame: Up to 7 days after vaccine booster dose
Adverse events with medical attention
Frequency, intensity and relatedness of adverse events with medical attention.
Time frame: Up to 12 months after vaccine booster dose

Other outcomes

Confirmed COVID-19 cases
Virologically confirmed COVID-19 cases 2 weeks after the booster
Time frame: From 14 days after booster to up to 12 months after vaccine booster dose
Possible case of VAERD
Possible cases of vaccine-associated enhanced respiratory disease (VAERD)
Time frame: From 14 days after booster to up to 12 months after vaccine booster dose

Study locations

6 sites

Instituto Aggeu Magalhães - Fundação Osvaldo Cruz - Pernambuco
Recife, Pernambuco 50670-420, Brazil
Centro de Pesquisa Clínica S
Serrana, São Paulo 14150-000, Brazil
Universidade Municipal de São Caetano do Sul
São Caetano Do Sul, São Paulo 09530-905, Brazil
Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.
Valinhos, São Paulo 13271-130, Brazil
Instituto Lóbus
Volta Redonda, São Paulo 27258-000, Brazil
Instituto Brasil de Pesquisa Clínica (IBPClin)
Rio de Janeiro, 20241-180, Brazil

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 6, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05354024
Lead sponsor: Butantan Institute
Responsible party: Sponsor
First posted: Apr 29, 2022
Start date: Feb 28, 2023
Primary completion: Oct 5, 2023
Completion: Sep 25, 2024
Last update: Feb 6, 2025

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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