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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04998240
Recruitment Status : Recruiting
First Posted : August 10, 2021
Last Update Posted : April 8, 2022
Sponsor:
Collaborators:
The Coalition for Epidemic Preparedness Innovations (CEPI)
Instituto Nacional de Saúde (INS), Mozambique
University of Antananarivo
International Centre for Diarrhoeal Disease Research, Bangladesh
Harvard University
Heidelberg University
Information provided by (Responsible Party):
International Vaccine Institute

Study Description
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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 in Mozambique.

Condition or disease Intervention/treatment Phase
Covid19 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), Biological: Placebo - Normal saline (0.9% sodium chloride solution) Phase 2

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 in Mozambique 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Single (Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Prevention
Official Title: A Phase 2, Observer-blind, Randomized Study to Assess the Safety and Immunogenicity of Heterologous Prime-boost COVID-19 Vaccines Regimens in Individuals Aged 18 to 65 Years in Mozambique.
Actual Study Start Date : December 29, 2021
Estimated Primary Completion Date : May 28, 2023
Estimated Study Completion Date : July 30, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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).
 Biological: 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 to 8' C


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 to 8'C
Experimental: 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).
 Biological: 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 to 8' C
Experimental: 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).
 Biological: 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 to 8' C


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 to 8'C
Experimental: 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).
 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 to 8'C


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 to +30°C


Outcome Measures
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Primary Outcome Measures :
  1. Geometric Mean Titers (GMTs) of anti-SARS-CoV-2 neutralizing antibodies [ Time Frame: Four Weeks after second dose ]
    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.

  2. Incidence of SAEs and AESI observed at any time point during the entire study period [ Time Frame: Till 12 months follow-up visit ]
    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

  3. Incidence of solicited reactions within 7 days (local reactions) and 14 days (systemic reactions) [ Time Frame: Within 7 days (local reactions) and 14 days (systemic reactions) following each vaccination ]
    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.

  4. Incidence of unsolicited adverse events that are within 28 days after each vaccination [ Time Frame: 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.

  5. Incidence of changes in laboratory safety measures from baseline to day 28 after each vaccination [ Time Frame: Within 28 days 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


Secondary Outcome Measures :
  1. Geometric Mean Titers (GMTs) and Geometric Mean Fold Rise (GMFR) [ Time Frame: Till 12 months follow-up visit ]
    • GMTs of anti-SARS-CoV-2 neutralizing antibodies as measured by neutralization assay at Day 0, Day 28, Day 196, Day 364
    • GMFR from baseline of anti-SARS-CoV-2 neutralizing antibodies as measured by neutralization assay at Day 0, Day 28, Day 196, Day 364
    • Percentage of participants achieving 4-fold or more rise from baseline of anti-SARS-CoV-2 neutralizing antibodies as measured by neutralization assay at Day 0, Day 28, Day 196, Day 364

  2. Geometric Mean Titers (GMTs) and Geometric Mean Fold Rise (GMFR) [ Time Frame: Till 12 months follow-up visit ]
    • GMTs of anti-SARS-CoV-2 anti-spike IgG as measured by Enzyme-Linked Immunosorbent Assay (ELISA), anti-SARS-CoV-2 pseudoneutralizing antibodies as measured by pseudo-neutralization assay, and anti-SARS-CoV-2 anti-nucleocapsid IgG at Day 0, Day 28, Day 56, Day 196, Day 364
    • GMFR from baseline of anti-SARS-CoV-2 anti-spike IgG as measured by Enzyme-Linked Immunosorbent Assay (ELISA), anti-SARS-CoV-2 pseudo-neutralizing antibodies as measured by pseudo-neutralization assay, and anti-SARS-CoV-2 anti-nucleocapsid IgG at Day 0, Day 28, Day 56, Day 196, Day 364
    • Percentage of participants achieving 4-fold or more rise from baseline for anti-SARS-CoV-2 anti-spike IgG as measured by Enzyme-Linked Immunosorbent Assay (ELISA), anti-SARS-CoV-2 pseudoneutralizing antibodies as measured by pseudo-neutralization assay, and anti-SARS-CoV-2 anti-nucleocapsid IgG at Day 0, Day 28, Day 56, Day 196, Day 364


Other Outcome Measures:
  1. Cellular immune responses against SARS-CoV-2 [ Time Frame: Till 12 months follow-up visit ]
    Cellular immune responses against SARS-CoV-2 by ELISpot and by Intracellular Cytokine Staining (ICS) (Th1/Th2) at days 0, 14, 28, 42, 56, 196, 364, following immunization with heterologous and homologous prime-boost COVID-19 vaccines regimens, in the participants of immunology cohort.

  2. GMTs, GMFR from baseline [ Time Frame: Till 12 months follow-up visit ]
    • GMTs of anti-SARS-CoV-2 anti-spike IgG, anti-nucleocapsid IgG against SARS-CoV-2, nAbs and pnAbs against SARS-CoV-2, cellular immune response against SARS-CoV-2, post prime or boost dose, and within one week in all participants being found to be SARS-CoV-2 positive by testing.
    • GMFR from baseline of anti-SARS-CoV-2 anti-spike IgG, anti-nucleocapsid IgG against SARS-CoV-2, nAbs and pnAbs against SARS-CoV-2, cellular immune response against SARS-CoV-2, post prime or boost dose, and within one week in all participants being found to be SARS-CoV-2 positive by testing.
    • Percentage of participants achieving 4-fold or more rise from baseline for anti-SARS-CoV-2 anti-spike IgG, anti-nucleocapsid IgG against SARS-CoV-2, nAbs and pnAbs against SARS-CoV-2, cellular immune response against SARS-CoV-2, post prime or boost dose, and within one week in all participants being found to be SARS-CoV-2 positive by testing.

  3. Genome sequencing of SARS-CoV-2 viruses isolated post prime or booster dose [ Time Frame: After diagnosis of SARS-CoV-2 infection ]
    Genome sequencing of SARS-CoV-2 viruses isolated post prime or boost, after diagnosis of SARS-CoV-2 infection, in all study participants of heterologous and homologous prime-boost COVID-19 vaccines regimens

  4. Profile of vaccine-induced humoral response against SARS-CoV-2 [ Time Frame: Till 12 months follow-up visit ]
    Profile of vaccine-induced humoral response against SARS-CoV-2 using systems serology at days 0, 14, 28, 42, 56, 196, 364, in study participants of immunology subset cohort, following immunization with heterologous and homologous prime-boost COVID-19 vaccines regimens.


Eligibility Criteria
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Individuals aged 18 to 65 years old at the time of consent.
  • Residing within the Maputo health region 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.
  • History of laboratory confirmed COVID-19 illness prior to enrollment (History of SARS-Cov-2 detection by PCR or antibody to SARS-CoV-2) within past 12 months.
  • SARS-CoV-2 seropositivity at screening.
  • 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04998240


Contacts
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Contact: Florian Marks, PhD +821087033813 fmarks@ivi.int
Contact: Birkneh Tilahun Tadesse, PhD +821098041348 birkneh.tadesse@ivi.int

Locations
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Mozambique
Centro de Investigação e Treino em Saúde da Polana Caniço - Instituto Nacional de Saúde Recruiting
Maputo, Mozambique
Contact: Ilesh Jani, PhD    +258825802221    ilesh.jani@ins.gov.mz   
Sponsors and Collaborators
International Vaccine Institute
The Coalition for Epidemic Preparedness Innovations (CEPI)
Instituto Nacional de Saúde (INS), Mozambique
University of Antananarivo
International Centre for Diarrhoeal Disease Research, Bangladesh
Harvard University
Heidelberg University
Investigators
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Principal Investigator: Florian Marks, PhD International Vaccine Institute
Principal Investigator: Ilesh Jani, PhD Instituto Nacional de Saúde
More Information
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Additional Information:

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Responsible Party: International Vaccine Institute
ClinicalTrials.gov Identifier: NCT04998240    
Other Study ID Numbers: IVI-ECOVA-02
First Posted: August 10, 2021    Key Record Dates
Last Update Posted: April 8, 2022
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by International Vaccine Institute:
SARS-CoV-2, Vaccines, Mix and Match Trial
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
 Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Myeloma Proteins
Paraproteins
Immunologic Factors
Physiological Effects of Drugs