CompletedNCT04993209ADAPTCOVUpdated Aug 21, 2023

Clinical Trial of the COVID-19 Vaccine (Recombinant, Inactivated) in Brazil

A Phase 1 interventional study of NDV-HXP-S 1μg and NDV-HXP-S 3μg in Coronavirus Infections and Healthy, sponsored by Butantan Institute. Completed at 1 site in Brazil. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-08-21.

Sponsored by Butantan Institute · Phase 1, Interventional, and Prevention

Phase: Phase 1
Study type: Interventional
Enrollment: 320
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 S protein from SARS-CoV-2 stabilized in pre-fusion form with Hexapro technology.

This vaccine was successfully tested in non-clinical study 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 aims, to respond to several regulatory requirements to advance the clinical development of the product through a dose-escalation, controlled, randomized, adult clinical trial. The results of the Phase I (former Stage A), allow us to base the decision to evaluate the safety and immunogenicity of three doses of HDV-HXP-S (1μg, 3μg or 10μg).

Conditions studied

Coronavirus Infections
Healthy

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Keywords

Vaccine
SARS-CoV-2
COVID-19

In context

Coronavirus Infections

952 studies on the registry are indexed under Coronavirus Infections; 50 are open to participants now.

This study's enrollment of 320 is above the median of 110 across 549 interventional studies indexed under Coronavirus Infections.

Browse Coronavirus Infections studies →

Lead sponsor

Butantan Institute is the lead sponsor of 31 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

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Adults aged between 18 and 59 years at the time of consent;
Agree to periodical contacts via phone, electronic means and home visits;
Good health conditions (absence of a clinically significant medical condition, acute or chronic, determined by medical history, physical examination, and clinical evaluation by the investigator);
Body Mass Index (BMI) of 17 to 40 kg/m² at the time of screening;
Intention of participating in the study by signing the Informed Consent Form;
A negative result for antibody testing against SARS-CoV-2 by CLIA performed within 7 days prior to study immunization;
No history of COVID-19 diagnosed by RT-PCR or antigen testing at screening visit and therefore within 72 hours prior to study enrollment;
No history of vaccination against COVID-19.

Exclusion criteria

Use any product under investigation within 90 days prior to randomization or plan to use a product during the period of participation in the study;
Have received vaccine in the last 28 days prior to inclusion in the study, or have immunization scheduled throughout the study period;
Evidences of uncontrolled active neurological, cardiac, pulmonary, hepatic or renal disease, according to anamnesis or physical examination. Significant changes in treatment or hospitalizations due to worsening of the condition in the last three months are indicators of uncontrolled disease;
Have a history of severe allergic reaction or anaphylaxis to the vaccine or study vaccine components;
History of being allergic to chicken or eggs;
History of angioedema or anaphylactic reaction;
Have suspected or confirmed fever within 72 hours prior to vaccination or an axillary temperature above 37.8°C* on the day of vaccination (inclusion may be delayed until participant completes 72 hours without fever);
Altered vital signs, clinically relevant in the opinion of the principal investigator;
Neoplastic diseases (except basal cell carcinoma and cervical carcinoma in situ);
Suspected or confirmed diseases with compromised immune system including: congenital or acquired immunodeficiencies and uncontrolled autoimmune diseases according to anamnesis or physical examination. Significant changes in treatment or hospitalizations due to worsening of the condition in the last three months are indicators of uncontrolled disease;
Make use of immunosuppressive therapies six months prior to inclusion in the study or schedule use of immunosuppressants within two years of inclusion in the study. The dose of corticosteroids considered immunosuppressive is the equivalent to prednisone at a dose of 2,0 mg/kg/day for adults, for more than a week. The continuous use of topical or nasal corticosteroids is not considered immunosuppressive. The following therapies are considered immunosuppressive: antineoplastic drugs, radiotherapy, immunosuppressants to induce tolerance to transplants, among others.
Have received blood products (transfusions or immunoglobulins) in the last three months prior to inclusion in the study, or schedule administration of blood products or immunoglobulins within two years of inclusion in the study.
Have a history of bleeding disorders (e.g., clotting factor deficiency, coagulopathy, platelet dysfunction), or prior history of significant bleeding or bruising after IM injection or venipuncture;
Have a history of any alcohol or drug abuse in the last 12 months prior to inclusion in the study that has caused medical, professional or family problems, as indicated by the clinical history;
Behavioral, cognitive, or psychiatric illness that, in the opinion of the principal investigator or medical representative, affects the participant's ability to understand and collaborate with the requirements of the study protocol;
The participant is a member of the team conducting the study or is in a dependent relationship with one of the members of the team conducting the study. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings, parents), as well as employees or students who are directly dependent on the Researcher or local personnel conducting the study;
Any other condition that, in the opinion of the principal investigator or medical representative, may jeopardize the safety or rights of a potential participant or prevent them from complying with this protocol.
Abnormalities in screening laboratory tests considered to be exclusionary in the opinion of the principal investigator or medical representative. Grade 1 alterations are considered non-significant unless the principal investigator or medical representative indicates otherwise. If any alteration in the tests is considered temporary, the tests may be repeated in up to three opportunities during the screening period;
Positive serological tests for the human immunodeficiency virus (ELISA anti-HIV1/2); Hepatitis B (HbsAg or Anti-HBc) or Hepatitis C (total ELISA anti-HCV);
For females:
Pregnancy (confirmed by a positive β-hCG test), breastfeeding and/or expressing intention to engage in sexual practices with reproductive potential without using a contraceptive method in the three months following vaccination
- The temperature measured with a temporal thermometer is considered equivalent to the axillary temperature.

Study design

Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Care provider, Investigator)
Enrollment: 320 participants (actual)

Study arms

Experimental
NDV-HXP-S 1μg
NDV-HXP-S 1μg with an interval of 28 days apart. A dose escalation will be performed with an interval of two days between each dose in a blinded form. The aim is to verify the product safety and support the decision on the dose selection among three alternatives, 1 μg, 3 μg and 10 μg, based on the immune response evaluation. These results will also explore the response against two variants of concern in SARS-CoV-2: γ and β. The Phase I (former stage A) is designed as a non-inferiority test comparing the three different doses.
Biological: NDV-HXP-S 1μg
Experimental
NDV-HXP-S 3μg
NDV-HXP-S 3μg with an interval of 28 days apart. A dose escalation will be performed with an interval of two days between each dose in a blinded form. The aim is to verify the product safety and support the decision on the dose selection among three alternatives, 1 μg, 3 μg and 10 μg, based on the immune response evaluation. These results will also explore the response against two variants of concern in SARS-CoV-2: γ and β. The Phase I (former stage A) is designed as a non-inferiority test comparing the three different doses.
Biological: NDV-HXP-S 3μg
Experimental
NDV-HXP-S 10μg
NDV-HXP-S 10μg/0.5mL intramuscularly, with an interval of 28 days apart. A dose escalation will be performed with an interval of two days between each dose in a blinded form. The aim is to verify the product safety and support the decision on the dose selection among three alternatives, 1 μg, 3 μg and 10 μg, based on the immune response evaluation. These results will also explore the response against two variants of concern in SARS-CoV-2: γ and β. The Phase I (former stage A) is designed as a non-inferiority test comparing the three different doses.
Biological: NDV-HXP-S 10μg
Active comparator
Adsorbed inactivated COVID-19 vaccine (CoronaVac)
Adsorbed inactivated COVID-19 vaccine 600 SU dose (0.5 mL) with an interval of 28 days apart Intramuscular (deltoid). In the original version of protocol, the control arm consisted in placebo use. There was a changing post hoc to Adsorbed inactivated COVID-19 vaccine (CoronaVac) due to decision of Data and Safety Monitoring Board, when 219 (50% of original sample) subjects have already included in the study. Therefore, those who received a placebo at the first vaccine visit started to receive active control vaccine and those who were included from that moment forward received two doses of active control vaccine. The original study protocol provided for the inclusion of the placebo arm (10% of population of study), in order to serve as a control for safety evaluations and to assess the attack rate of natural infection to which participants will be exposed during the study.
Other: Adsorbed inactivated COVID-19 vaccine (CoronaVac)

Interventions

BiologicalNDV-HXP-S 1μg
NDV-HXP-S 1μg 0.5mL 2 doses intramuscular (deltoid) 28 days apart
BiologicalNDV-HXP-S 3μg
NDV-HXP-S 3μg 0.5mL 2 doses intramuscular (deltoid) 28 days apart
BiologicalNDV-HXP-S 10μg
NDV-HXP-S 10μg 0.5mL 2 doses intramuscular (deltoid) 28 days apart
OtherAdsorbed inactivated COVID-19 vaccine (CoronaVac)
Adsorbed inactivated COVID-19 vaccine 600 SU/0.5 mL 2 doses intramuscular (deltoid) 28 days apart

What researchers measure

Primary outcomes

Safety: Adverse reactions.
Number and intensity of solicited local and systemic adverse reactions.
Time frame: 7 days after each vaccination.
Safety: Laboratory evaluations
Number, severity and summary of clinically significant changes of hematological (hemoglobin \[g/dL\], white blood cells \[cells/mm³\] and platelets \[count per mm³\]) and biochemical evaluations (creatinine \[mg/dL\], AST \[U/L\], ALT \[U/L\], and total bilirubin \[mg/dL\]) since the baseline within 7 days after each vaccination.
Time frame: 7 days after each vaccination.
Immunogenicity: Percentage of seroconversion.
Percentage of positive SARS-CoV-2 pseudovirus neutralization assay in a participant with a baseline negative result (Wuhan strain).
Time frame: 42(+7) days after the first dose.
Immunogenicity: Neutralization GMT SARS-CoV-2 pseudovirus.
Neutralization GMT against SARS-CoV-2 pseudovirus (Wuhan strain)
Time frame: 28 days after the first vaccination.
Immunogenicity: Neutralization GMT SARS-CoV-2 pseudovirus.
Neutralization GMT against SARS-CoV-2 pseudovirus (Wuhan strain)
Time frame: 14 days after the second vaccination.
Immunogenicity: Neutralization GMT SARS-CoV-2 pseudovirus.
Neutralization GMT against SARS-CoV-2 pseudovirus (beta and gamma strains)
Time frame: 42(+7) days after the first dose.

Secondary outcomes

Safety: all unsolicited adverse reactions.
Number, intensity, and relatedness of all unsolicited adverse reactions.
Time frame: 28 days after each vaccination.
Safety: serious and medically-attended adverse reactions.
Number, intensity, and relatedness of serious adverse reactions
Time frame: Throughout the entire study period.
Safety: events of special interest.
Number, intensity, and relatedness of events of special interest.
Time frame: Throughout the entire study period.
Immunogenicity: Levels of antibodies.
Levels of antibodies against SARS-CoV-2 Nucleocapsid protein and RBD
Time frame: At baseline, 28 days after the first vaccination, and 14 days after the second vaccination, and 3, 6, 9, and 12 months after first vaccination.
Immunogenicity: Neutralization GMT of SARS-CoV-2 pseudovirus.
Neutralization GMT against SARS-CoV-2 pseudovirus per age group
Time frame: 28 days after the first vaccination, and 14 days after the second vaccination.
Exploratory Endpoints: Levels of antibodies.
Levels of antibodies against SARS-CoV-2 Nucleocapsid protein and RBD.
Time frame: At baseline, 28 days after the first vaccination, and 14 days after the second vaccination, and 3 months, 6 months, 9 months, and 12 months after first vaccination.
Exploratory Endpoints: Neutralization GMT of SARS-CoV-2 pseudovirus.
Neutralization GMT against SARS-CoV-2 pseudovirus at 3 months, 6 months, 9 months, and 12 months after first vaccination in subjects.
Time frame: at 3 months, 6 months, 9 months, and 12 months after first vaccination in subjects.
Exploratory Endpoints - COVID-19 cases.
Number and intensity of COVID-19 cases diagnosed.
Time frame: 14 days after first and second vaccination.

Study locations

1 site

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
Ribeirão Preto, São Paulo 14015-069, Brazil

References and documents

Publications

Peixoto de Miranda EJF, Calado RT, Boulos FC, de Sousa Moreira JA, Machado FF, Almeida MAALDS, Da Rocha MCO, Infante V, Mercer LD, Hjorth R, Scharf R, White J, Polyak C, Raghunandan R, Garcia-Sastre A, Sun W, Palese P, Krammer F, Innis B, Pereira CG, Kallas EG. Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Results of a randomized vaccine-controlled phase I ADAPTCOV trial in Brazil. Vaccine. 2025 Apr 11;52:126680. doi: 10.1016/j.vaccine.2024.126680. Epub 2025 Mar 3. PubMed 40037239 ↗

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Jul 2021 to primary completion in Dec 2021, 5 months.

Of 50 phase 1 interventional studies under Coronavirus Infections, half reached primary completion within 7 months of starting (the median), counting those still running; a quarter within 3 and three quarters within 17. This study's 5 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered: Aug 3, 2021
First posted: Aug 6, 2021
StartActual: Jul 9, 2021
Primary completionActual: Dec 10, 2021
CompletionActual: Nov 4, 2022
Last update: Aug 21, 2023

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Aug 21, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04993209
Lead sponsor: Butantan Institute
Responsible party: Sponsor
First posted: Aug 6, 2021
Start date: Jul 9, 2021
Primary completion: Dec 10, 2021
Completion: Nov 4, 2022
Last update: Aug 21, 2023

Study contacts

Fernanda Castro Boulos, MD,PhD

study director · Butantan Institute

Oversight

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

View the source record on ClinicalTrials.gov ↗

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