Clinical Trial of the COVID-19 Vaccine (Recombinant, Inactivated) in Brazil
- Conditions
- HealthyCoronavirus Infections
- Interventions
- Biological: NDV-HXP-S 3μgBiological: NDV-HXP-S 1μgBiological: NDV-HXP-S 10μgOther: Adsorbed inactivated COVID-19 vaccine (CoronaVac)
- Registration Number
- NCT04993209
- Lead Sponsor
- Butantan Institute
- Brief 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.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 320
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NDV-HXP-S 3μg 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. NDV-HXP-S 1μg 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. NDV-HXP-S 10μg 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. Adsorbed inactivated COVID-19 vaccine (CoronaVac) 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.
- Primary Outcome Measures
Name Time Method Safety: Adverse reactions. 7 days after each vaccination. Number and intensity of solicited local and systemic adverse reactions.
Safety: Laboratory evaluations 7 days after each vaccination. 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.
Immunogenicity: Neutralization GMT SARS-CoV-2 pseudovirus. 42(+7) days after the first dose. Neutralization GMT against SARS-CoV-2 pseudovirus (beta and gamma strains)
Immunogenicity: Percentage of seroconversion. 42(+7) days after the first dose. Percentage of positive SARS-CoV-2 pseudovirus neutralization assay in a participant with a baseline negative result (Wuhan strain).
- Secondary Outcome Measures
Name Time Method Immunogenicity: Levels of antibodies. 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. Levels of antibodies against SARS-CoV-2 Nucleocapsid protein and RBD
Safety: serious and medically-attended adverse reactions. Throughout the entire study period. Number, intensity, and relatedness of serious adverse reactions
Safety: events of special interest. Throughout the entire study period. Number, intensity, and relatedness of events of special interest.
Safety: all unsolicited adverse reactions. 28 days after each vaccination. Number, intensity, and relatedness of all unsolicited adverse reactions.
Exploratory Endpoints: Neutralization GMT of SARS-CoV-2 pseudovirus. at 3 months, 6 months, 9 months, and 12 months after first vaccination in subjects. Neutralization GMT against SARS-CoV-2 pseudovirus at 3 months, 6 months, 9 months, and 12 months after first vaccination in subjects.
Exploratory Endpoints - COVID-19 cases. 14 days after first and second vaccination. Number and intensity of COVID-19 cases diagnosed.
Exploratory Endpoints: Levels of antibodies. 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. Levels of antibodies against SARS-CoV-2 Nucleocapsid protein and RBD.
Immunogenicity: Neutralization GMT of SARS-CoV-2 pseudovirus. 28 days after the first vaccination, and 14 days after the second vaccination. Neutralization GMT against SARS-CoV-2 pseudovirus per age group
Trial Locations
- Locations (1)
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
🇧🇷Ribeirão Preto, São Paulo, Brazil