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

COVID-19 Clinical Trial

Official title:

Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule With mRNA and Inactivated COVID-19 Vaccines: a Single-blinded, Randomized, Parallel Group Superiority Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05668065
• Other study ID #: TN2021-NAT-INS-70
• Status: Completed
• Phase: Phase 3
• Start date: November 22, 2021
• Est. completion date: June 25, 2022

Study information

• Verified date: January 2023
• Source: Institut Pasteur de Tunis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This study is a randomized simple-blinded comparative phase III clinical trial in COVID-19 vaccine naïve volunteers adults aged between 18 and 60 years. 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. The study is conducted in four different sites located in the North of Tunisia. A total of 240 eligible participants were included. Among them, the primary end point data were available for 100 participants randomly allocated to heterologous boost group versus 99 participants randomly allocated to homologous boost dose group. Participants are assigned to receive either two injections of the CoronaVac vaccine (1st and 2nd vaccine), or CoronaVac as 1st dose and Pfizer as 2nd dose in 3 to 4 weeks interval. A blood sample (5ml of the whole blood) is collected for each participant at the vaccination center before the first dose injection. After verifying the absence of a SARS-CoV-2 infection during the interrogation (a follow-up survey), a 2nd blood sample (5ml of whole blood) is taken for each participant at the vaccination center before the second dose injection. After the two injections, a 3rd blood sample (5ml of whole blood) will be taken for each participant between day 21 and day 35 after the second dose. Data collection and all samples are treated at Institute Pasteur of Tunis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 199
• Est. completion date: June 25, 2022
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Acceptance to participate in the study.
• Age: 18-60 years old.

Non-inclusion criteria:

• Presence of disability (mainly mental disability).
• Pregnancy.
• Patients under immunosuppressive treatment or immunocompromised individuals.
• Prior Covid-19 infection.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Biological:
• CoronaVac/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.
• 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

Locations

Country	Name	City	State
Tunisia	Géant supermarket (Governorate of Ariana)	Ariana	Mnihla
Tunisia	Vaccination center of Ariana	Ariana
Tunisia	Leoni factory (Governorate of Bizerte)	Bizerte	Mateur
Tunisia	Institut Pasteur de Tunis	Tunis
Tunisia	STEG head office (Governorate of Tunis)	Tunis

Sponsors (1)

Lead Sponsor	Collaborator
Institut Pasteur de Tunis

Country where clinical trial is conducted

Tunisia, 

References & Publications (7)

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. Erratum In: Lancet. 2021 Aug 14;398(10300):582. — View Citation

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. — View Citation

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. Erratum In: Lancet Microbe. 2021 Aug 4;: — View Citation

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. Erratum In: Lancet. 2021 May 18;: — View Citation

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. — View Citation

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. Erratum In: Lancet. 2022 Jan 29;399(10323):436. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Immunogenicity parameters (Neutralizing antibody and IgG antibody titers) between day 21 and day 35	The level of neutralizing antibodies and anti-spike IgG antibody responses	Between day 21 and day 35 after the second dose of vaccination
Secondary	Immunogenicity parameters (Neutralizing antibody and IgG antibody titers) at day 0 (at baseline)	The level of neutralizing antibodies and anti-spike IgG antibody responses	At day 0 (at baseline)
Secondary	Immunogenicity parameters (Neutralizing antibody and IgG antibody titers) at day 21 +/- 3 days	The level of neutralizing antibodies and anti-spike IgG antibody responses	At day 21 +/- 3 days after the first dose of vaccination
Secondary	Safety indexes of adverse reactions at day 30	The incidence of adverse reactions at day 30 of the second dose of vaccination	At day 30 after the second dose of vaccination