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

NCT04993209 | Completed Phase 1 DMC

• 1 other identifier: NCV-01-IB
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronavirus Infections; Healthy

Keywords

Vaccine; SARS-CoV-2; COVID-19

Outcome Measures

Primary Outcomes (6)

• Safety: Adverse reactions.

  Number and intensity of solicited local and systemic adverse reactions.

  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.

  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).

  42(+7) days after the first dose.

• Immunogenicity: Neutralization GMT SARS-CoV-2 pseudovirus.

  Neutralization GMT against SARS-CoV-2 pseudovirus (Wuhan strain)

  28 days after the first vaccination.

• Immunogenicity: Neutralization GMT SARS-CoV-2 pseudovirus.

  Neutralization GMT against SARS-CoV-2 pseudovirus (Wuhan strain)

  14 days after the second vaccination.

• Immunogenicity: Neutralization GMT SARS-CoV-2 pseudovirus.

  Neutralization GMT against SARS-CoV-2 pseudovirus (beta and gamma strains)

  42(+7) days after the first dose.

Secondary Outcomes (8)

• Safety: all unsolicited adverse reactions.

  28 days after each vaccination.

• Safety: serious and medically-attended adverse reactions.

  Throughout the entire study period.

• Safety: events of special interest.

  Throughout the entire study period.

• 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.

• Immunogenicity: Neutralization GMT of SARS-CoV-2 pseudovirus.

  28 days after the first vaccination, and 14 days after the second vaccination.

Study Arms (4)

NDV-HXP-S 1μg

EXPERIMENTAL

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

NDV-HXP-S 3μg

EXPERIMENTAL

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

NDV-HXP-S 10μg

EXPERIMENTAL

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

Adsorbed inactivated COVID-19 vaccine (CoronaVac)

ACTIVE COMPARATOR

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

NDV-HXP-S 1μg BIOLOGICAL

NDV-HXP-S 1μg 0.5mL 2 doses intramuscular (deltoid) 28 days apart

NDV-HXP-S 1μg

NDV-HXP-S 3μg BIOLOGICAL

NDV-HXP-S 3μg 0.5mL 2 doses intramuscular (deltoid) 28 days apart

NDV-HXP-S 3μg

NDV-HXP-S 10μg BIOLOGICAL

NDV-HXP-S 10μg 0.5mL 2 doses intramuscular (deltoid) 28 days apart

NDV-HXP-S 10μg

Adsorbed inactivated COVID-19 vaccine (CoronaVac) OTHER

Adsorbed inactivated COVID-19 vaccine 600 SU/0.5 mL 2 doses intramuscular (deltoid) 28 days apart

Adsorbed inactivated COVID-19 vaccine (CoronaVac)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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;
• 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;
• 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;
• 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.
• 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

Sponsors & Collaborators

• Butantan Institute: lead

Study Sites (1)

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Ribeirão Preto, São Paulo, 14015-069, Brazil

Location

Related Publications (1)

• 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.

  PMID: 40037239 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Interventions

NDV-HXP-S COVID-19 vaccine; sinovac COVID-19 vaccine

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Fernanda Castro Boulos, MD,PhD

  Butantan Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: An electronic central randomization system will be used to designate the investigational product (IP) that each participant must receive. A team study non-blind, qualified member (nurse/pharmacist) will obtain the corresponding randomization, will separate the respective IP, will blind the product and deliver it to blind staff. The product will be in a syringe that is in a blister labeled with the sponsor's name, IP code, administration route, IP dose and expiration date. The study non-blind staff will not have contact with the participants, will not have access to identification data or any other involvement with the study, besides randomizing the participant, separating the syringe containing placebo or vaccine, checking if the information on the blister label corresponds the information on the cartridge label and the syringe is labeled with the clinical trial code, ID, corresponding visit and investigator's name. Blinding is maintained with the opacity of the label.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Stage A (blinding form) will verify the product safety and support the decision on the dose selection among 1 μg, 3 μg and 10 μg, based on the immune response assessment. These results will also explore the response against 2 variants of concern in SARS-CoV-2: γ and β.

Study Record Dates

• First Submitted: August 3, 2021
• First Posted: August 6, 2021
• Study Start: July 9, 2021
• Primary Completion: December 10, 2021
• Study Completion: November 4, 2022
• Last Updated: August 21, 2023

Record last verified: 2023-08

Locations

BR (1)