Mix and Match Heterologous Prime-Boost Study Using Approved COVID-19 Vaccines in Mozambique
Study Details
Study Description
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 |
|---|---|---|
|
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
Arms and Interventions
| 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
Primary Outcome Measures
- Geometric Mean Titers (GMTs) of anti-SARS-CoV-2 neutralizing antibodies [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.
- Incidence of SAEs and AESI observed at any time point during the entire study period [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
- Incidence of solicited reactions within 7 days (local reactions) and 14 days (systemic reactions) [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.
- Incidence of unsolicited adverse events that are within 28 days after each vaccination [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.
- Incidence of changes in laboratory safety measures from baseline to day 28 after each vaccination [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
- Geometric Mean Titers (GMTs) and Geometric Mean Fold Rise (GMFR) [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
- Geometric Mean Titers (GMTs) and Geometric Mean Fold Rise (GMFR) [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
- Cellular immune responses against SARS-CoV-2 [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.
- GMTs, GMFR from baseline [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.
- Genome sequencing of SARS-CoV-2 viruses isolated post prime or booster dose [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
- Profile of vaccine-induced humoral response against SARS-CoV-2 [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
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.
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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.
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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.
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Continuous use of the anticoagulants, such as coumarins and related anticoagulants.
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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.
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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.
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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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centro de Investigação e Treino em Saúde da Polana Caniço - Instituto Nacional de Saúde | Maputo | Mozambique |
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
- Principal Investigator: Florian Marks, PhD, International Vaccine Institute
- Principal Investigator: Ilesh Jani, PhD, Instituto Nacional de Saúde
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- IVI-ECOVA-02