Covid19
Conditions
Keywords
SARS-CoV-2, Vaccines, Mix and Match Trial
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.
Interventions
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
BIOLOGICALAd26.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
BIOLOGICALPlacebo - 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
Sponsors
The Coalition for Epidemic Preparedness Innovations (CEPI)
Instituto Nacional de Saúde, Mozambique
University of Antananarivo
International Centre for Diarrhoeal Disease Research, Bangladesh
Harvard University
Heidelberg University
International Vaccine Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
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.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Madagascar, Mozambique
Outcome results
None listed