Mix and Match Heterologous Prime-Boost Study Using Approved COVID-19 Vaccines

NCT ID: NCT04998240

Last Updated: 2023-04-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-29
• Study Completion Date: 2024-02-28

Brief Summary

This is an observer-blind, randomized study which aims to assess the immune response and the safety of two different approved vaccines for first and second dose in healthy adults.

Detailed Description

This is a phase 2, observer-blind, randomized study to assess the safety and the immunogenicity of heterologous prime-boost COVID-19 vaccines regimens in healthy adults aged 18 to 65 years using two approved vaccines (Sinopharm / CNBG Vaccine (BBIBP-CorV) and Johnson & Johnson Vaccine (Ad26.COV2.S)).

The study will consist of 2 cohorts, one for main immunology endpoints (N=260, 65 per study arm) and one for more detailed immunological assessment (N=100, 25 per study arm). Two doses of vaccine will be administered intramuscularly 4 week apart. All the study participants will be follow-up for 12 months from the administration of first vaccine dose.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Prime BBIBP-CorV, Boost Ad26.COV2.S (A1)

The randomized study participants will receive Prime BBIBP-CorV vaccine followed by Booster dose of Ad26.COV2.S vaccine (A1).

Group Type: EXPERIMENTAL

BBIBP-CorV - Inactivated SARS-CoV-2 vaccine (Vero cell)

Intervention Type: BIOLOGICAL

The Inactivated SARS-CoV-2 vaccine (Vero cell)- BBIBP-CorV manufactured by Beijing Institute of Biological Products (BIBP), China National Biotec Group (CNBG), Sinopharm, Beijing, People's Republic of China

Dose formulation: A liquid formulation containing 4μg total protein with aluminum hydroxide adjuvant (0·45 mg/mL) per 0·5 mL (2-dose schedule followed by a booster dose).

Mode of Administration:

Intramuscular

Storage Conditions: 2°C to 8°C

Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein),

Intervention Type: BIOLOGICAL

Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein), manufactured by Johnson and Johnson in the United States of America.

Dose formulation: One dose (0.5 ml) contains contains 5 x 10 10 virus particles

Mode of administration: Intramuscular

Storage Conditions: 2°C to 8°C

Prime BBIBP-CorV, Boost BBIBP-CorV (A2)

The randomized study participants will receive Prime BBIBP-CorV vaccine followed by Booster dose of BBIBP-CorV vaccine (A2).

Group Type: EXPERIMENTAL

BBIBP-CorV - Inactivated SARS-CoV-2 vaccine (Vero cell)

Intervention Type: BIOLOGICAL

The Inactivated SARS-CoV-2 vaccine (Vero cell)- BBIBP-CorV manufactured by Beijing Institute of Biological Products (BIBP), China National Biotec Group (CNBG), Sinopharm, Beijing, People's Republic of China

Dose formulation: A liquid formulation containing 4μg total protein with aluminum hydroxide adjuvant (0·45 mg/mL) per 0·5 mL (2-dose schedule followed by a booster dose).

Mode of Administration:

Intramuscular

Storage Conditions: 2°C to 8°C

Prime Ad26.COV2.S, Boost BBIBP-CorV (B1)

The randomized study participants will receive Prime Ad26.COV2.S vaccine followed by Booster dose of BBIBP-CorV vaccine (B1).

Group Type: EXPERIMENTAL

BBIBP-CorV - Inactivated SARS-CoV-2 vaccine (Vero cell)

Intervention Type: BIOLOGICAL

The Inactivated SARS-CoV-2 vaccine (Vero cell)- BBIBP-CorV manufactured by Beijing Institute of Biological Products (BIBP), China National Biotec Group (CNBG), Sinopharm, Beijing, People's Republic of China

Dose formulation: A liquid formulation containing 4μg total protein with aluminum hydroxide adjuvant (0·45 mg/mL) per 0·5 mL (2-dose schedule followed by a booster dose).

Mode of Administration:

Intramuscular

Storage Conditions: 2°C to 8°C

Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein),

Intervention Type: BIOLOGICAL

Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein), manufactured by Johnson and Johnson in the United States of America.

Dose formulation: One dose (0.5 ml) contains contains 5 x 10 10 virus particles

Mode of administration: Intramuscular

Storage Conditions: 2°C to 8°C

Prime Placebo, Boost Ad26.COV2.S (B2)

The randomized study participants will receive Prime Placebo vaccine followed by Booster dose of Ad26.COV2.S (B2).

Group Type: EXPERIMENTAL

Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein),

Intervention Type: BIOLOGICAL

Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein), manufactured by Johnson and Johnson in the United States of America.

Dose formulation: One dose (0.5 ml) contains contains 5 x 10 10 virus particles

Mode of administration: Intramuscular

Storage Conditions: 2°C to 8°C

Placebo - Normal saline (0.9% sodium chloride solution)

Intervention Type: BIOLOGICAL

Placebo - Normal saline (0.9% sodium chloride solution)

Dose formulation: Not Applicable

Mode of administration: Intramuscular

Storage conditions: 15°C to 30°C

Interventions

BBIBP-CorV - Inactivated SARS-CoV-2 vaccine (Vero cell)

The Inactivated SARS-CoV-2 vaccine (Vero cell)- BBIBP-CorV manufactured by Beijing Institute of Biological Products (BIBP), China National Biotec Group (CNBG), Sinopharm, Beijing, People's Republic of China

Dose formulation: A liquid formulation containing 4μg total protein with aluminum hydroxide adjuvant (0·45 mg/mL) per 0·5 mL (2-dose schedule followed by a booster dose).

Mode of Administration:

Intramuscular

Storage Conditions: 2°C to 8°C

Intervention Type: BIOLOGICAL

Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein),

Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein), manufactured by Johnson and Johnson in the United States of America.

Dose formulation: One dose (0.5 ml) contains contains 5 x 10 10 virus particles

Mode of administration: Intramuscular

Storage Conditions: 2°C to 8°C

Intervention Type: BIOLOGICAL

Placebo - Normal saline (0.9% sodium chloride solution)

Placebo - Normal saline (0.9% sodium chloride solution)

Dose formulation: Not Applicable

Mode of administration: Intramuscular

Storage conditions: 15°C to 30°C

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Individuals aged 18 to 65 years old at the time of consent.
• Residing within the area of the study and planning to stay for the study duration.
• HIV negative test result on the day of screening (for those who do not have a documented HIV test results in the last three months of screening).
• Female volunteers of childbearing potential with a negative pregnancy test on the day(s) of screening and vaccination, practicing/willing to practice continuous effective contraception* recommended by the National Health System up to 12 weeks after the booster vaccination..
• Agreement to refrain from blood donation during the course of the study.
• Able and willing to comply with all study requirements, based on the assessment of the investigator.
• Willingness to provide written informed consent before any trial procedure * Effective contraception is defined as follows: contraceptive medications delivered orally, intramuscularly, vaginally, or implanted underneath the skin, surgical methods (hysterectomy or bilateral tubal ligation), condoms, diaphragms, intrauterine device (IUD), and abstinence.

Exclusion Criteria

• Pregnancy, lactation, or intention to become pregnant during the vaccination phase through three months after the booster dose.
• Prior receipt/ planned receipt of any vaccine other than the study intervention within 28 days before and after each study vaccination.
• Previous participation in any COVID-19 vaccination trial or vaccination campaign.
• Administration of immunoglobulins and/ or any blood products within the three months preceding the administration of the study vaccine.
• Known infection with hepatitis B, C virus.
• Known history of allergy or anaphylaxis to study vaccine components and/or excipients or other medications, or any other allergies deemed by the investigator to increase the risk of an adverse reaction.
• History of bleeding disorder (e.g., factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.
• Continuous use of the anticoagulants, such as coumarins and related anticoagulants.
• Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, renal disease, liver disease, endocrine disorders, and neurological illness (mild/moderate well controlled comorbidities are allowed).
• Any clinically significant abnormal finding on screening as judged by the investigator.
• Confirmed SARS-CoV-2 infection at enrollment.
• Any confirmed or suspected immunosuppressive or immunodeficient state, asplenia, recurrent severe infections and chronic use (more than 14 days) immunosuppressant medication within 3 months prior to recruitment (topical steroids are allowed).
• Any other finding which in the opinion of the investigators would increase the risk of an adverse outcome from participation in the trial or result in incomplete or poor-quality data.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Coalition for Epidemic Preparedness Innovations (CEPI)

UNKNOWN

Sponsor Role: collaborator

Instituto Nacional de Saúde, Mozambique

OTHER_GOV

Sponsor Role: collaborator

University of Antananarivo

UNKNOWN

Sponsor Role: collaborator

International Centre for Diarrhoeal Disease Research, Bangladesh

OTHER

Sponsor Role: collaborator

Harvard University

OTHER

Sponsor Role: collaborator

Heidelberg University

OTHER

Sponsor Role: collaborator

International Vaccine Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Florian Marks, PhD

Role: PRINCIPAL_INVESTIGATOR

International Vaccine Institute

Ilesh Jani, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Saúde, Mozambique

Raphael Rakotozandrindrainy, MD

Role: PRINCIPAL_INVESTIGATOR

Madagascar Institute for Vaccine Research (MIVR), University of Antananarivo

Locations

Madagascar Institute for Vaccine Research (MIVR), University of Antananarivo

Antananarivo, , Madagascar

Centro de Investigação e Treino em Saúde da Polana Caniço - Instituto Nacional de Saúde

Maputo, , Mozambique

Countries

Madagascar; Mozambique

References

Ramgi P, Siribie M, Rakotozandrindrainy N, Bule O, Shrivastava H, Chambule L, Park EL, Fernando C, Boque J, Macuiana R, Razafimanantsoa R, Rakotozandrindrainy N, Razafindrabe TJL, Rakotoarisoa AN, Raminosoa TM, Derandrainy HL, Rakotoson MM, de Silva CSS, Mutombene M, Massinga C, Langa JP, Guarnacci T, Kang SSY, Jo SK, Jeon HJ, Excler JL, Yang Y, Wang S, Sugimoto JD, Yang JS, Shim BS, Binger T, Capitine IU, Aziz AB, Park JY, Kim DR, Rakotozandrindrainy R, Jani IV, Tadesse BT, Marks F. Immunogenicity and Safety of Heterologous Versus Homologous Prime-Boost Regimens With BBIBP-CorV and Ad26.COV2.S COVID-19 Vaccines: A Multicentric, Randomized, Observer-Blinded Non-inferiority Trial in Madagascar and Mozambique. Clin Infect Dis. 2025 Jul 22;80(Supplement_1):S37-S46. doi: 10.1093/cid/ciaf130.

Reference Type: DERIVED

PMID: 40694514 (View on PubMed)

Related Links

https://covid19.who.int/region/afro/country/mz

Description Mozambique COVID-19 Situation

Other Identifiers

IVI-ECOVA-02

Identifier Type: -

Identifier Source: org_study_id