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

NCT04998240 | Unknown Phase 2 DMC

• 1 other identifier: IVI-ECOVA-02
• Study Type: interventional
• Target: 360
• Locations: 2 countries
• Sites: 2

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.

Conditions

Covid19

Keywords

SARS-CoV-2, Vaccines, Mix and Match Trial

Outcome Measures

Primary Outcomes (5)

• Geometric Mean Titers (GMTs) of anti-SARS-CoV-2 neutralizing antibodies

  Geometric Mean Titers (GMTs) of anti-SARS-CoV-2 neutralizing antibodies using a neutralization assay four weeks after the second dose, in COVID-19 seronegative participants following immunization with heterologous and homologous prime-boost COVID-19 vaccines regimens.

  Four Weeks after second dose

• Incidence of SAEs and AESI observed at any time point during the entire study period

  Incidence of SAEs and AESI observed at any time point during the entire study period, among all study participants of heterologous and homologous prime-boost COVID-19 vaccines regimens

  Till 12 months follow-up visit

• Incidence of solicited reactions within 7 days (local reactions) and 14 days (systemic reactions)

  Incidence of solicited reactions within 7 days (local reactions) and 14 days (systemic reactions) following each vaccination in all study participants of heterologous and homologous prime-boost COVID-19 vaccines regimens.

  Within 7 days (local reactions) and 14 days (systemic reactions) following each vaccination

• Incidence of unsolicited adverse events that are within 28 days after each vaccination

  Incidence of unsolicited adverse events that are within 28 days after each vaccination in all study participants of heterologous and homologous prime-boost COVID-19 vaccines regimens.

  Within 28 days after each vaccination

• Incidence of changes in laboratory safety measures from baseline to day 28 after each vaccination

  Incidence of changes in laboratory safety measures from baseline to day 28 after each vaccination, in all study participants of heterologous and homologous prime-boost COVID-19 vaccines regimens

  Within 28 days after each vaccination

Secondary Outcomes (2)

• Geometric Mean Titers (GMTs) and Geometric Mean Fold Rise (GMFR)

  Till 12 months follow-up visit

• Geometric Mean Titers (GMTs) and Geometric Mean Fold Rise (GMFR)

  Till 12 months follow-up visit

Other Outcomes (4)

• Cellular immune responses against SARS-CoV-2

  Till 12 months follow-up visit

• GMTs, GMFR from baseline

  Till 12 months follow-up visit

• Genome sequencing of SARS-CoV-2 viruses isolated post prime or booster dose

  After diagnosis of SARS-CoV-2 infection

Study Arms (4)

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

EXPERIMENTAL

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

Biological: BBIBP-CorV - Inactivated SARS-CoV-2 vaccine (Vero cell); Biological: Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein),

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

EXPERIMENTAL

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

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

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

EXPERIMENTAL

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

Biological: BBIBP-CorV - Inactivated SARS-CoV-2 vaccine (Vero cell); Biological: Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein),

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

EXPERIMENTAL

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

Biological: Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein),; Biological: Placebo - Normal saline (0.9% sodium chloride solution)

Interventions

BBIBP-CorV - Inactivated SARS-CoV-2 vaccine (Vero cell) 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); Prime BBIBP-CorV, Boost Ad26.COV2.S (A1); Prime BBIBP-CorV, Boost BBIBP-CorV (A2)

Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein), 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 Ad26.COV2.S, Boost BBIBP-CorV (B1); Prime BBIBP-CorV, Boost Ad26.COV2.S (A1); Prime Placebo, Boost Ad26.COV2.S (B2)

Placebo - Normal saline (0.9% sodium chloride solution) BIOLOGICAL

Placebo - Normal saline (0.9% sodium chloride solution) Dose formulation: Not Applicable Mode of administration: Intramuscular Storage conditions: 15°C to 30°C

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• International Vaccine Institute: lead
• The Coalition for Epidemic Preparedness Innovations (CEPI): collaborator
• Instituto Nacional de Saúde, Mozambique: collaborator
• University of Antananarivo: collaborator
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator
• Harvard University: collaborator
• Heidelberg University: collaborator

Study Sites (2)

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

Antananarivo, 101, Madagascar

Location

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

Maputo, Mozambique

Location

Related Publications (1)

• 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.

  PMID: 40694514 DERIVED

Related Links

• Description Mozambique COVID-19 Situation

MeSH Terms

Conditions

COVID-19

Interventions

Ad26COVS1; Sodium Chloride

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)

COVID-19 Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Florian Marks, PhD

  International Vaccine Institute

  PRINCIPAL INVESTIGATOR

• Ilesh Jani, PhD

  Instituto Nacional de Saúde, Mozambique

  PRINCIPAL INVESTIGATOR

• Raphael Rakotozandrindrainy, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This is an observer-blind study. So in this study only the outcome assessors should be blinded namely the clinical staff in charge of the clinical outcomes assessment and the laboratory analysts.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The primary analysis of this study will be a non-inferiority comparison between heterologous versus homologous boost arms 4 weeks after second vaccination within each group of the studied COVID-19 vaccines, i.e., the A1 arm (BBIBP-CorV, Ad26.COV2.S) will be compared with the A2 arm (BBIBP-CorV, BBIBP-CorV), and the B1 arm (Ad26.COV2.S, BBIBP-CorV) will be compared with the B2 arm (Placebo, Ad26.COV2.S). All 360 participants will be used for the primary analysis and the secondary analysis.

Study Record Dates

• First Submitted: July 29, 2021
• First Posted: August 10, 2021
• Study Start: December 29, 2021
• Primary Completion: September 26, 2022
• Study Completion: February 28, 2024
• Last Updated: April 19, 2023

Record last verified: 2023-04

Locations

MA (1); MO (1)