Phase Ⅲ, Clinical Trial to Compare an Inactivated Quadrivalent Influenza Vaccine and a Licensed Vaccine in Chile

Influenza Clinical Trial

— TetraFluVac  

Official title:

A Phase III, Randomized, Double-blind and Controlled Clinical Trial to Evaluate the Immunogenicity and Safety of Influenza Vaccine, Inactivated, Quadrivalent Developed by Sinovac Biotech Co., Ltd. Compared to a Licensed Quadrivalent Influenza Vaccine, VaxigripTetra™, in Individuals Aged 3 Years and Older in Chile

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05494047
• Other study ID #: PRO-QINF-3004
• Status: Recruiting
• Phase: Phase 3
• Start date: July 14, 2022
• Est. completion date: July 31, 2023

Study information

• Verified date: August 2022
• Source: Pontificia Universidad Catolica de Chile
• Contact: Pablo A Gonzalez, PhD
• Phone: +56226862842
• Email: pagonzalez[@]bio.puc.cl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study compares the immunogenity and safety of quadrivalent inactivated influenza vaccines. The experimental group receives the quadrivalent influenza vaccine developed by Sinovac Biotech Co., Ltd and the control group immunized with Vaxigrip Tetra™. The group has 1600 persons from general population 3 years and older. The design is double-blind and randomized. The primary outcome is the immunogenicity against the 4 strains of influenza included in both vaccines.

Description:

The study is designed to evaluate the immunogenicity of the quadrivalent inactivated-virus influenza vaccine developed by Sinovac Biotech Co., Ltd against Vaxigrip Tetra™. The population included in the study is healthy subjects 3 years and older, being 800 individuals 10 years old or less and 800 over 18 years, randomized 1:1 to experimental vaccine or Vaxigrip Tetra™. Volunteers 8 years old or less, without history of previous influenza infection will receive 2 doses of vaccine, al other individuals will receipt 1 dose of vaccine. Immunogenicity will be assessed one month after the last dose of vaccine, humoral responses will be determined for all patients meanwhile ome subgroup of patients will have a determination of cellular immunity also. Subjects will be follow up for one month, adverse events will be assessed during this time.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1600
• Est. completion date: July 31, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Years and older

Eligibility

Inclusion Criteria:

1. Volunteers age 3 years and older, in good health or medically stable;

2. Written informed consent obtained from subjects or/and legal guardian;

3. No receipt of influenza vaccines within 6 months or plans to receive any influenza vaccines during the study;

4. Female subjects of non-childbearing may be enrolled in the study. Nonchildbearing potential is defined as surgically sterile (history of bilateral tubal ligation, bilateral oophorectomy, hysterectomy) or premenarche or postmenopausal (defined as amenorrhea for = 12 consecutive months prior to screening without an alternative medical cause).

5. Female subjects of childbearing potential may be enrolled in the study, if the

subject:

• Has a negative pregnancy test on the day of the first dose (day 0);
• Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose and until at least 28 days after vaccination.

Exclusion Criteria:

1. History of seasonal influenza within 6 months prior to the study entry;

2. Axillary temperature =37.3?;

3. History of Guillain-Barré syndrome within 6 weeks of receipt of prior influenza vaccine.

4. History of allergy to any vaccine, or any ingredient of the experimental vaccine.

5. Serious adverse reaction(s) to the vaccine, such as urticaria, dyspnea or angioneurotic edema, etc.;

6. History of serious neurological disorder (such as epilepsy, convulsions, etc.) , or mental illness;

7. Autoimmune disease or immunodeficiency/immunosuppressive, or any immunosuppressant receipt within 6 months prior to the study entry;

8. Significant chronic illnesses that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion (may include, but are not limited to cardiovascular disease, hypertension and diabetes that cannot be controlled by drugs, liver or kidney disorders, HIV infection or malignant tumor;

9. Acute central nervous system diseases such as encephalitis/myelitis, acute disseminating encephalomyelitis, and related disorders;

10. Absence of spleen, functional absence of spleen, and absence or removal of spleen under any circumstances;

11. Diagnosed coagulation function abnormal (e.g., coagulation factor deficiency, coagulation disorder, or platelet abnormalities), or obvious bruising or coagulation disorders;

12. Alcoholism or history of drug abuse

13. Acute disease or acute stage of chronic disease within 7 days prior to study entry;

14. Received blood products within 3 months prior to study entry;

15. Received any live attenuated vaccine within 14 days prior to study entry or any subunit vaccine or inactivated vaccine within 7 days prior to study entry;

16. Pregnant women or lactating women;

17. Subjects participate other clinical trials (licensed or unlicensed vaccines, drugs, organisms, devices, blood products or drugs) during the study period;

18. Any other factors which are unsuitable for participation in the clinical trial as judged by the investigator. -

Related Conditions & MeSH terms

• Influenza
• Influenza, Human
• Vaccines

Intervention

Drug:
• Tetravalent influenza vaccine developed by Sinovac Biotech Co.
15µg Hemagglutinin Antigen (HA) of each of the four strains

Locations

Country	Name	City	State
Chile	Centro de Investigaciones Médicas Respiratorias (CIMER)	Providencia	Metropolitana
Chile	Hospital Puerto Montt	Puerto Montt	Los Lagos
Chile	Hospital Clínico UC Christus	Santiago	Metropolitana
Chile	Hospital Félix Bulnes	Santiago	Metropolitana
Chile	Clínica Alemana de Santiago	Vitacura	Metropolitana

Sponsors (3)

Lead Sponsor	Collaborator
Pontificia Universidad Catolica de Chile	Sinovac Biotech (Chile) SpA, Sinovac Biotech Co., Ltd

Country where clinical trial is conducted

Chile, 

References & Publications (9)

Beran J, Peeters M, Dewé W, Raupachová J, Hobzová L, Devaster JM. Immunogenicity and safety of quadrivalent versus trivalent inactivated influenza vaccine: a randomized, controlled trial in adults. BMC Infect Dis. 2013 May 20;13:224. doi: 10.1186/1471-2334-13-224. — View Citation

Cadorna-Carlos JB, Nolan T, Borja-Tabora CF, Santos J, Montalban MC, de Looze FJ, Eizenberg P, Hall S, Dupuy M, Hutagalung Y, Pépin S, Saville M. Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial. Vaccine. 2015 May 15;33(21):2485-92. doi: 10.1016/j.vaccine.2015.03.065. Epub 2015 Apr 2. — View Citation

Claeys C, Drame M, García-Sicilia J, Zaman K, Carmona A, Tran PM, Miranda M, Martinón-Torres F, Thollot F, Horn M, Schwarz TF, Behre U, Merino JM, Sadowska-Krawczenko I, Szymanski H, Schu P, Neumeier E, Li P, Jain VK, Innis BL. Assessment of an optimized manufacturing process for inactivated quadrivalent influenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults. BMC Infect Dis. 2018 Apr 18;18(1):186. doi: 10.1186/s12879-018-3079-8. — View Citation

Greenberg DP, Robertson CA, Noss MJ, Blatter MM, Biedenbender R, Decker MD. Safety and immunogenicity of a quadrivalent inactivated influenza vaccine compared to licensed trivalent inactivated influenza vaccines in adults. Vaccine. 2013 Jan 21;31(5):770-6. doi: 10.1016/j.vaccine.2012.11.074. Epub 2012 Dec 8. — View Citation

Jain VK, Domachowske JB, Wang L, Ofori-Anyinam O, Rodríguez-Weber MA, Leonardi ML, Klein NP, Schlichter G, Jeanfreau R, Haney BL, Chu L, Harris JS, Sarpong KO, Micucio AC, Soni J, Chandrasekaran V, Li P, Innis BL. Time to Change Dosing of Inactivated Quadrivalent Influenza Vaccine in Young Children: Evidence From a Phase III, Randomized, Controlled Trial. J Pediatric Infect Dis Soc. 2017 Mar 1;6(1):9-19. doi: 10.1093/jpids/piw068. — View Citation

Lee BY, Bartsch SM, Willig AM. The economic value of a quadrivalent versus trivalent influenza vaccine. Vaccine. 2012 Dec 14;30(52):7443-6. doi: 10.1016/j.vaccine.2012.10.025. Epub 2012 Oct 19. Erratum in: Vaccine. 2013 May 7;31(20):2477-9. — View Citation

Mallory RM, Yu J, Kameo S, Tanaka M, Rito K, Itoh Y, Dubovsky F. The safety and efficacy of quadrivalent live attenuated influenza vaccine in Japanese children aged 2-18 years: Results of two phase 3 studies. Influenza Other Respir Viruses. 2018 Jul;12(4):438-445. doi: 10.1111/irv.12555. Epub 2018 Apr 10. — View Citation

Reed C, Meltzer MI, Finelli L, Fiore A. Public health impact of including two lineages of influenza B in a quadrivalent seasonal influenza vaccine. Vaccine. 2012 Mar 2;30(11):1993-8. doi: 10.1016/j.vaccine.2011.12.098. Epub 2012 Jan 5. — View Citation

Vaccines against influenza WHO position paper - November 2012. Wkly Epidemiol Rec. 2012 Nov 23;87(47):461-76. English, French. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events (AEs)	Local and systemic AEs	Solicited AEs within 7 days after each dose and unsolicited AEs within 28 days after each dose
Other	Serious adverse events	Ocurrence and relationship of serious adverse events	Within 28 days after each dose
Primary	Seroconversion for influenza	Seroconversion rates and geometric mean titers of human influenza antibody for each of the four antigens.	28 days after the last dose of vaccination
Secondary	Antibody titer 1:40 or more	Proportion of subjects with antibody titer =1:40	28 days after the last dose of vaccination
Secondary	Cellular immunity-ELISPOT	Quantification by ELISPOT of specific Spot Forming Cells for cytokines, molecules and immunoglobulins induced by both vaccines	28 days after the last dose
Secondary	Cellular immunity-Cytometry	Quantification by flow cytometry of CD3+CD4+ and CD3+CD8+ cells positive for Activation Induced Markers, induced by both vaccines.	28 days after the last dose
Secondary	Cellular immunity-Luminex (TM)	• Quantification by Luminex® of cytokines secreted by specific CD3+CD4+ and CD3+CD8+ cells induced by each vaccine	28 days after the last dose