Clinical trial NCT04993209: Clinical Trial of the COVID-19 Vaccine (Recombinant, Inactivated) in Brazil
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Coronavirus Infections
Healthy
Keywords: Vaccine
SARS-CoV-2
COVID-19
Lead sponsor: Butantan Institute
Sponsor class: OTHER_GOV
First posted: 2021-08-06
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: PREVENTION

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).

Eligibility criteria: 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 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

    * The temperature measured with a temporal thermometer is considered equivalent to the axillary temperature.

Primary outcomes:
measure: Safety: Adverse reactions.
timeFrame: 7 days after each vaccination.
measure: Safety: Laboratory evaluations
timeFrame: 7 days after each vaccination.
measure: Immunogenicity: Percentage of seroconversion.
timeFrame: 42(+7) days after the first dose.
measure: Immunogenicity: Neutralization GMT SARS-CoV-2 pseudovirus.
timeFrame: 28 days after the first vaccination.
measure: Immunogenicity: Neutralization GMT SARS-CoV-2 pseudovirus.
timeFrame: 14 days after the second vaccination.
measure: Immunogenicity: Neutralization GMT SARS-CoV-2 pseudovirus.
timeFrame: 42(+7) days after the first dose.
Secondary outcomes:
measure: Safety: all unsolicited adverse reactions.
timeFrame: 28 days after each vaccination.
measure: Safety: serious and medically-attended adverse reactions.
timeFrame: Throughout the entire study period.
measure: Safety: events of special interest.
timeFrame: Throughout the entire study period.
measure: Immunogenicity: Levels of antibodies.
timeFrame: 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.
measure: Immunogenicity: Neutralization GMT of SARS-CoV-2 pseudovirus.
timeFrame: 28 days after the first vaccination, and 14 days after the second vaccination.
measure: Exploratory Endpoints: Levels of antibodies.
timeFrame: 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.
measure: Exploratory Endpoints: Neutralization GMT of SARS-CoV-2 pseudovirus.
timeFrame: at 3 months, 6 months, 9 months, and 12 months after first vaccination in subjects.
measure: Exploratory Endpoints - COVID-19 cases.
timeFrame: 14 days after first and second vaccination.
Other outcomes:
Locations:
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
state: São Paulo
Study officials:
affiliation: Butantan Institute
name: Fernanda Castro Boulos, MD,PhD
role: STUDY_DIRECTOR
References: