Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule With mRNA and Inactivated COVID-19 Vaccines

NCT05668065 | Completed Phase 3 DMC

• 1 other identifier: TN2021-NAT-INS-70
• Study Type: interventional
• Target: 199
• Locations: 1 country
• Sites: 5

Brief Summary

This study is a randomized, simple-blinded comparative phase III clinical trial comparing the immunogenicity of two doses Coronovac to that of a first dose of Coronovac (Sinovac, Beijing, China) followed by a booster shot with the mRNA-based BNT162b2 SARS-CoV-2 vaccine (Comirnaty, Pfizer-BioNTech). The purpose of this study is to evaluate the superiority, safety and immunogenicity of the heterologous prime-boost CoronaVac/BNT162b2 vaccination to the homologous CoronaVac/CoronaVac regimen.

Conditions

COVID-19

Keywords

Vaccine; Immunogenicity; Heterologous prime-boost; Coronavac; Pfizer-BioNtech

Outcome Measures

Primary Outcomes (1)

• Superiority of the heterologous prime-boost immunization with mRNA vaccine after vaccination with an inactivated vaccine versus homologous immunization with inactivated vaccines

  The primary end point for immunogenicity was the serum neutralizing antibody level with a percentage of inhibition at 90% at 21-35 days after boost. A difference of 25% between groups was considered clinically relevant.

  Between day 21 and day 35 after the second dose of vaccination

Secondary Outcomes (4)

• Immunogenicity parameters (Neutralizing antibody and IgG antibody titers) between day 21 and day 35

  Between day 21 and day 35 after the second dose of vaccination

• Immunogenicity parameters (Neutralizing antibody and IgG antibody titers) at day 0 (at baseline)

  At day 0 (at baseline)

• Immunogenicity parameters (Neutralizing antibody and IgG antibody titers) at day 21 +/- 3 days

  At day 21 +/- 3 days after the first dose of vaccination

• Safety indexes of adverse reactions at day 30

  At day 30 after the second dose of vaccination

Study Arms (2)

CoronaVac/CoronaVac

EXPERIMENTAL

Biological: Coronavac Two doses at 21-day +/- 3 days. Each innoculation dose is 0.5 ml containing 600 SU in-house unit (equals to 3μg) of SARS-CoV-2 antigen.

Biological: CoronaVac/CoronaVac

CoronaVac/BNT162b2

ACTIVE COMPARATOR

Biological: CoronaVac/BNT162b2 First dose of Coronavac. Each innoculation dose is 0.5 ml containing 600 SU in-house unit (equals to 3μg) of SARS-CoV-2 antigen. Second dose of BNT162b2 at 21-day +/- 3 days. Each dose of the Pfizer-BioNTech COVID-19 Vaccine is 0.3 ml. Each prefilled syringe contains 30 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2.

Biological: CoronaVac/BNT162b2

Interventions

CoronaVac/CoronaVac BIOLOGICAL

Two doses at 21-day +/- 3 days. Each innoculation dose is 0.5 ml containing 600 SU in-house unit (equals to 3μg) of SARS-CoV-2 antigen.

CoronaVac/CoronaVac

CoronaVac/BNT162b2 BIOLOGICAL

First dose of Coronavac. Each innoculation dose is 0.5 ml containing 600 SU in-house unit (equals to 3μg) of SARS-CoV-2 antigen. Second dose of BNT162b2 at 21-day +/- 3 days. Each dose of the Pfizer-BioNTech COVID-19 Vaccine is 0.3 ml. Each prefilled syringe contains 30 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2

CoronaVac/BNT162b2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Acceptance to participate in the study.
• Age: 18-60 years old.
• Presence of disability (mainly mental disability).
• Pregnancy.
• Patients under immunosuppressive treatment or immunocompromised individuals.
• Prior Covid-19 infection.

You may not qualify if:

• Occurrence of a serious adverse event (death, anaphylactic shock, ...).
• Subjects wishing to withdraw from the study.
• Occurrence of a SARS-CoV-2 symptomatic infection during the follow-up period.

Sponsors & Collaborators

• Institut Pasteur de Tunis: lead

Study Sites (5)

Leoni factory (Governorate of Bizerte)

Bizerte, Mateur, 7030, Tunisia

Location

Géant supermarket (Governorate of Ariana)

Aryanah, Mnihla, 2094, Tunisia

Location

Vaccination center of Ariana

Aryanah, 2080, Tunisia

Location

STEG head office (Governorate of Tunis)

Tunis, 1000, Tunisia

Location

Institut Pasteur de Tunis

Tunis, 1002, Tunisia

Location

Related Publications (7)

• Tanriover MD, Doganay HL, Akova M, Guner HR, Azap A, Akhan S, Kose S, Erdinc FS, Akalin EH, Tabak OF, Pullukcu H, Batum O, Simsek Yavuz S, Turhan O, Yildirmak MT, Koksal I, Tasova Y, Korten V, Yilmaz G, Celen MK, Altin S, Celik I, Bayindir Y, Karaoglan I, Yilmaz A, Ozkul A, Gur H, Unal S; CoronaVac Study Group. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet. 2021 Jul 17;398(10296):213-222. doi: 10.1016/S0140-6736(21)01429-X. Epub 2021 Jul 8.

  PMID: 34246358 BACKGROUND

• Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, Subbarao K, Kent SJ, Triccas JA, Davenport MP. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021 Jul;27(7):1205-1211. doi: 10.1038/s41591-021-01377-8. Epub 2021 May 17.

  PMID: 34002089 BACKGROUND

• Souza WM, Amorim MR, Sesti-Costa R, Coimbra LD, Brunetti NS, Toledo-Teixeira DA, de Souza GF, Muraro SP, Parise PL, Barbosa PP, Bispo-Dos-Santos K, Mofatto LS, Simeoni CL, Claro IM, Duarte ASS, Coletti TM, Zangirolami AB, Costa-Lima C, Gomes ABSP, Buscaratti LI, Sales FC, Costa VA, Franco LAM, Candido DS, Pybus OG, de Jesus JG, Silva CAM, Ramundo MS, Ferreira GM, Pinho MC, Souza LM, Rocha EC, Andrade PS, Crispim MAE, Maktura GC, Manuli ER, Santos MNN, Camilo CC, Angerami RN, Moretti ML, Spilki FR, Arns CW, Addas-Carvalho M, Benites BD, Vinolo MAR, Mori MAS, Gaburo N, Dye C, Marques-Souza H, Marques RE, Farias AS, Diamond MS, Faria NR, Sabino EC, Granja F, Proenca-Modena JL. Neutralisation of SARS-CoV-2 lineage P.1 by antibodies elicited through natural SARS-CoV-2 infection or vaccination with an inactivated SARS-CoV-2 vaccine: an immunological study. Lancet Microbe. 2021 Oct;2(10):e527-e535. doi: 10.1016/S2666-5247(21)00129-4. Epub 2021 Jul 8.

  PMID: 34258603 BACKGROUND

• Vacharathit V, Aiewsakun P, Manopwisedjaroen S, Srisaowakarn C, Laopanupong T, Ludowyke N, Phuphuakrat A, Setthaudom C, Ekronarongchai S, Srichatrapimuk S, Wongsirisin P, Sangrajrang S, Imsuwansri T, Kirdlarp S, Nualkaew S, Sensorn I, Sawaengdee W, Wichukchinda N, Sungkanuparph S, Chantratita W, Kunakorn M, Rojanamatin J, Hongeng S, Thitithanyanont A. CoronaVac induces lower neutralising activity against variants of concern than natural infection. Lancet Infect Dis. 2021 Oct;21(10):1352-1354. doi: 10.1016/S1473-3099(21)00568-5. Epub 2021 Aug 26. No abstract available.

  PMID: 34454652 BACKGROUND

• Lim WW, Mak L, Leung GM, Cowling BJ, Peiris M. Comparative immunogenicity of mRNA and inactivated vaccines against COVID-19. Lancet Microbe. 2021 Sep;2(9):e423. doi: 10.1016/S2666-5247(21)00177-4. Epub 2021 Jul 16. No abstract available.

  PMID: 34308395 BACKGROUND

• Shaw RH, Stuart A, Greenland M, Liu X, Nguyen Van-Tam JS, Snape MD; Com-COV Study Group. Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data. Lancet. 2021 May 29;397(10289):2043-2046. doi: 10.1016/S0140-6736(21)01115-6. Epub 2021 May 12. No abstract available.

  PMID: 33991480 BACKGROUND

• Borobia AM, Carcas AJ, Perez-Olmeda M, Castano L, Bertran MJ, Garcia-Perez J, Campins M, Portoles A, Gonzalez-Perez M, Garcia Morales MT, Arana-Arri E, Aldea M, Diez-Fuertes F, Fuentes I, Ascaso A, Lora D, Imaz-Ayo N, Baron-Mira LE, Agusti A, Perez-Ingidua C, Gomez de la Camara A, Arribas JR, Ochando J, Alcami J, Belda-Iniesta C, Frias J; CombiVacS Study Group. Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet. 2021 Jul 10;398(10295):121-130. doi: 10.1016/S0140-6736(21)01420-3. Epub 2021 Jun 25.

  PMID: 34181880 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

sinovac COVID-19 vaccine; BNT162 Vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus 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 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Simple-Blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Head of immunoallergology unit, Clinical Immunology Department

Model Details: Randomized simple-blinded comparative phase III clinical trial

Study Record Dates

• First Submitted: December 27, 2022
• First Posted: December 29, 2022
• Study Start: November 22, 2021
• Primary Completion: January 31, 2022
• Study Completion: June 25, 2022
• Last Updated: January 5, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

TU (5)