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

NCT05354024 | Completed Phase 2 DMC

• 1 other identifier: NCV-02-IB
• Study Type: interventional
• Target: 4,400
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Coronavirus Infections; Healthy

Keywords

Vaccine; SARS-CoV-2; COVID-19

Outcome Measures

Primary Outcomes (5)

• Solicited and unsolicited adverse reactions

  Frequency and intensity of local and systemic solicited and unsolicited adverse reactions.

  Within to 7 days after vaccination booster dose

• Unsolicited adverse reactions

  Frequency and intensity of all unsolicited grade ≥2 adverse reactions.

  Within 28 days after vaccination booster dose

• Severe adverse events

  Frequency, intensity and relatedness of severe adverse events.

  Within 28 days after vaccination booster dose

• Neutralization GMTR SARS-CoV-2 pseudovirus

  Neutralization of Geometric mean titer ratio (GMTR) SARS-CoV-2 pseudovirus.

  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.

  Up to 28 days after vaccination booster dose

Secondary Outcomes (14)

• GMT SARS-CoV-2 pseudovirus

  Up to 28 days after vaccination booster dose

• Neutralization GMFR SARS-CoV-2 pseudovirus

  Up to 28 days after vaccination booster dose

• GMTR against SARS-CoV-2 (ELISA)

  Up to 28 days after vaccination booster dose

• Seroconversion anti-SARS-CoV-2 ELISA

  Up to 28 days after vaccination booster dose

• GMFR against SARS-CoV-2 (ELISA)

  Up to 28 days after vaccination booster dose

Other Outcomes (2)

• Confirmed COVID-19 cases

  From 14 days after booster to up to 12 months after vaccine booster dose

• Possible case of VAERD

  From 14 days after booster to up to 12 months after vaccine booster dose

Study Arms (6)

NDV-HXP-S 10μg (Phase II)

EXPERIMENTAL

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

BNT162b2 30μg (Phase II)

ACTIVE COMPARATOR

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

NDV-HXP-S 10μg batch 1 (Phase III)

EXPERIMENTAL

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

NDV-HXP-S 10μg batch 2 (Phase III)

EXPERIMENTAL

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

NDV-HXP-S 10μg batch 3 (Phase III)

EXPERIMENTAL

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

BNT162b2 30μg (Phase III)

ACTIVE COMPARATOR

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

NDV-HXP-S 10μg BIOLOGICAL

NDV-HXP-S 10μg/0.5mL intramuscular (deltoid), 1 dose (booster)

NDV-HXP-S 10μg (Phase II); NDV-HXP-S 10μg batch 1 (Phase III); NDV-HXP-S 10μg batch 2 (Phase III); NDV-HXP-S 10μg batch 3 (Phase III)

BNT162b2 30μg BIOLOGICAL

Vaccine against COVID-19 BNT162b2 30μg/0.3mL intramuscular (deltoid), 1 dose (booster)

BNT162b2 30μg (Phase II); BNT162b2 30μg (Phase III)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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.
• 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:

Sponsors & Collaborators

• Butantan Institute: lead

Study Sites (6)

Instituto Aggeu Magalhães - Fundação Osvaldo Cruz - Pernambuco

Recife, Pernambuco, 50670-420, Brazil

Location

Universidade Municipal de São Caetano do Sul

São Caetano do Sul, São Paulo, 09530-905, Brazil

Location

Centro de Pesquisa Clínica S

Serrana, São Paulo, 14150-000, Brazil

Location

Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.

Valinhos, São Paulo, 13271-130, Brazil

Location

Instituto Lóbus

Volta Redonda, São Paulo, 27258-000, Brazil

Location

Instituto Brasil de Pesquisa Clínica (IBPClin)

Rio de Janeiro, 20241-180, Brazil

Location

Related Publications (1)

• Nakahashi-Ouchida R, Fujihashi K, Kurashima Y, Yuki Y, Kiyono H. Nasal vaccines: solutions for respiratory infectious diseases. Trends Mol Med. 2023 Feb;29(2):124-140. doi: 10.1016/j.molmed.2022.10.009. Epub 2022 Nov 23.

  PMID: 36435633 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Interventions

NDV-HXP-S COVID-19 vaccine; BNT162 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

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 2
• 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 active control 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Parallel Assignment in Phase II (1:1), that aims to evaluate safety and immunogenicity in 400 subjects. Phase III (3:1), that aims to evaluate safety in total population (n=4.000, 3000 in arm of NDV-HXP-S 10μg, 1000 subjects per each consecutive batch, and 1000 subjects in the active control arm), immunogenicity in a subcohort (n=1000) and consistency of three consecutive batches in part of the subcohort of immunogenicity correspondent only to the NDV-HXP-S 10μg arms (n=750).

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: April 29, 2022
• Study Start: February 28, 2023
• Primary Completion: October 5, 2023
• Study Completion: September 25, 2024
• Last Updated: February 6, 2025

Record last verified: 2024-02

Locations

BR (6)