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

Sponsor

Butantan Institute (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05354024

Collaborator

(none)

4,400

Enrollment

Location

Arms

Anticipated Duration (Months)

275

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronavirus Infections Healthy	Biological: NDV-HXP-S 10μg Biological: BNT162b2 30μg	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

4400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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).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).

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

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.

Primary Purpose:

Prevention

Official Title:

Phase II/III Double-blind, Randomized Clinical Trial With Active Vaccine Control to Evaluate the Safety, Immunogenicity, and Consistency of the Lots of Booster Dose of COVID-19 (Recombinant, Inactivated) Vaccine in Adults in Brazil

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Solicited and unsolicited adverse reactions [Within to 7 days after vaccination booster dose]
Frequency and intensity of local and systemic solicited and unsolicited adverse reactions.
Unsolicited grade >2 adverse reactions [Within 28 days after vaccination booster dose]
Frequency and intensity of all unsolicited grade ≥2 adverse reactions.
Severe adverse events [Within 28 days after vaccination booster dose]
Frequency, intensity and relatedness of severe adverse events.
Neutralization GMTR SARS-CoV-2 pseudovirus [Up to 14 days after vaccination booster dose]
Neutralization of Geometric mean titer ratio (GMTR) SARS-CoV-2 pseudovirus.
GMT against SARS-CoV-2 (ELISA) [Up to 14 days after vaccination booster dose]
Geometric mean titer (GMT) of Anti-SARS-CoV-2-S IgG antibodies (ELISA).

Secondary Outcome Measures

GMT SARS-CoV-2 pseudovirus [Up to 14 days after vaccination booster dose]
Neutralization of Geometric mean titer (GMT) SARS-CoV-2 pseudovirus.
Neutralization GMFR SARS-CoV-2 pseudovirus [Up to 14 days after vaccination booster dose]
Neutralization Geometric mean fold rise ratio (GMFR) SARS-CoV-2 pseudovirus.
Seroconversion Neutralization GMT SARS-CoV-2 pseudovirus [Up to 14 days after vaccination booster dose]
Percentage of subjects with Seroconversion Neutralization GMT SARS-CoV-2 pseudovirus.
GMTR against SARS-CoV-2 (ELISA) [Up to 14 days after vaccination booster dose]
Geometric mean titer ratio (GMTR) of Anti-SARS-CoV-2-S IgG antibodies (ELISA).
GMFR against SARS-CoV-2 (ELISA) [Up to 14 days after vaccination booster dose]
Geometric mean fold rise ratio (GMFR) of Anti-SARS-CoV-2-S IgG titers (ELISA).
Seroconversion anti-SARS-CoV-2 ELISA [Up to 14 days after vaccination booster dose]
Percentage of subjects with seroconversion of Anti-SARS-CoV-2 S IgG antibodies (ELISA).
GMT against SARS-CoV-2 (ELISA) [Up to 3 and 6 months after vaccine booster dose]
Geometric mean titer (GMT) of Anti-SARS-CoV-2-S IgG antibodies (ELISA).
Serious adverse events [Up to 6 months after vaccine booster dose]
Frequency, intensity and relatedness of serious adverse events.
Adverse events of special interest [Up to 6 months after vaccine booster dose]
Frequency, intensity and relatedness of adverse events of special interest.
Hematologic and biochemical assessments (Phase II) [Up to 7 days after vaccine booster dose]
Frequency, severity and relatedness of hematologic (hemoglobin, white blood cells and platelets) and biochemical (AST, ALT, bilirubins and creatinine) out of reference values.
Unsolicited adverse events [Up to 6 months after vaccine booster dose]
Frequency and intensity of all unsolicited adverse events.
Adverse events with medical attention [Up to 6 months after vaccine booster dose]
Frequency, intensity and relatedness of adverse events with medical attention.

Other Outcome Measures

Neutralization GMT against SARS-CoV-2 pseudovirus (variants of concern) [Up to 14 days after vaccination booster dose]
Neutralization of Geometric mean titer (GMT) against SARS-CoV-2 pseudovirus (variants of concern)
Confirmed COVID-19 cases [From 14 days after booster to up to 6 months after vaccine booster dose]
Virologically confirmed COVID-19 cases 2 weeks after the booster
Possible case of VAERD [From 14 days after booster to up to 6 months after vaccine booster dose]
Possible cases of vaccine-associated enhanced respiratory disease (VAERD)
T cell-mediated response [Up to 6 months after vaccine booster dose]
Vaccine-induced T cell immune response against SARS-CoV-2

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

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 SARS-CoV-2 infection status, with proof of two or more doses of inactive adsorbed vaccine against COVID-19, AZD1222 (ChAdOx1), or vaccine against COVID-19 BNT162b2 with or without a booster of vaccine against COVID-19 BNT162b2 or inactive adsorbed vaccine against COVID-19, of which the last dose administered at least 120 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:

Administration of a vaccine 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).
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, except Grade 1 changes unless otherwise indicated by the principal investigator.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.	Valinhos	São Paulo	Brazil	13271-130

Sponsors and Collaborators

Butantan Institute

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Butantan Institute

ClinicalTrials.gov Identifier:

NCT05354024

Other Study ID Numbers:

NCV-02-IB

First Posted:

Apr 29, 2022

Last Update Posted:

May 20, 2022

Last Verified:

May 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by Butantan Institute

Vaccine

SARS-CoV-2

COVID-19

Additional relevant MeSH terms:

COVID-19

Coronavirus Infections

Study Results

No Results Posted as of May 20, 2022