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

Healthy Clinical Trial

— ADAPTCOV  

Official title:

Double-blind, Randomized, With an Active Control Vaccine, Phase I Clinical Trial for Evaluation of Safety and Immunogenicity of a Recombinant Inactivated COVID-19 Vaccine in Adults in Brazil - ADAPTCOV

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04993209
• Other study ID #: NCV-01-IB
• Status: Completed
• Phase: Phase 1
• Start date: July 9, 2021
• Est. completion date: November 4, 2022

Study information

• Verified date: August 2023
• Source: Butantan Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: November 4, 2022
• Est. primary completion date: December 10, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria

1. Adults aged between 18 and 59 years at the time of consent;

2. Agree to periodical contacts via phone, electronic means and home visits;

3. 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);

4. Body Mass Index (BMI) of 17 to 40 kg/m² at the time of screening;

5. Intention of participating in the study by signing the Informed Consent Form;

6. A negative result for antibody testing against SARS-CoV-2 by CLIA performed within 7 days prior to study immunization;

7. No history of COVID-19 diagnosed by RT-PCR or antigen testing at screening visit and therefore within 72 hours prior to study enrollment;

8. No history of vaccination against COVID-19. Exclusion criteria

1. 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;

2. Have received vaccine in the last 28 days prior to inclusion in the study, or have immunization scheduled throughout the study period;

3. 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;

4. Have a history of severe allergic reaction or anaphylaxis to the vaccine or study vaccine components;

5. History of being allergic to chicken or eggs;

6. History of angioedema or anaphylactic reaction;

7. 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);

8. Altered vital signs, clinically relevant in the opinion of the principal investigator;

9. Neoplastic diseases (except basal cell carcinoma and cervical carcinoma in situ);

10. 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;

11. 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.

12. 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.

13. 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;

14. 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;

15. 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;

16. 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;

17. 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.

18. 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;

19. 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:

20. Pregnancy (confirmed by a positive ß-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.

Related Conditions & MeSH terms

• Coronavirus Infections
• COVID-19
• Healthy

Intervention

Biological:
• NDV-HXP-S 1µg
NDV-HXP-S 1µg 0.5mL 2 doses intramuscular (deltoid) 28 days apart
• NDV-HXP-S 3µg
NDV-HXP-S 3µg 0.5mL 2 doses intramuscular (deltoid) 28 days apart
• NDV-HXP-S 10µg
NDV-HXP-S 10µg 0.5mL 2 doses intramuscular (deltoid) 28 days apart

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

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	Ribeirão Preto	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Butantan Institute

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Adverse reactions.	Number and intensity of solicited local and systemic adverse reactions.	7 days after each vaccination.
Primary	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.
Primary	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.
Primary	Immunogenicity: Neutralization GMT SARS-CoV-2 pseudovirus.	Neutralization GMT against SARS-CoV-2 pseudovirus (Wuhan strain)	28 days after the first vaccination.
Primary	Immunogenicity: Neutralization GMT SARS-CoV-2 pseudovirus.	Neutralization GMT against SARS-CoV-2 pseudovirus (Wuhan strain)	14 days after the second vaccination.
Primary	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	Safety: all unsolicited adverse reactions.	Number, intensity, and relatedness of all unsolicited adverse reactions.	28 days after each vaccination.
Secondary	Safety: serious and medically-attended adverse reactions.	Number, intensity, and relatedness of serious adverse reactions	Throughout the entire study period.
Secondary	Safety: events of special interest.	Number, intensity, and relatedness of events of special interest.	Throughout the entire study period.
Secondary	Immunogenicity: Levels of antibodies.	Levels of antibodies against SARS-CoV-2 Nucleocapsid protein and RBD	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.
Secondary	Immunogenicity: Neutralization GMT of SARS-CoV-2 pseudovirus.	Neutralization GMT against SARS-CoV-2 pseudovirus per age group	28 days after the first vaccination, and 14 days after the second vaccination.
Secondary	Exploratory Endpoints: Levels of antibodies.	Levels of antibodies against SARS-CoV-2 Nucleocapsid protein and RBD.	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.
Secondary	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.	at 3 months, 6 months, 9 months, and 12 months after first vaccination in subjects.
Secondary	Exploratory Endpoints - COVID-19 cases.	Number and intensity of COVID-19 cases diagnosed.	14 days after first and second vaccination.