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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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 and Madagascar.

Conditions
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Covid19

Intervention / Treatment
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* 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)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prime BBIBP-CorV, Boost Ad26.COV2.S (A1)<br>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)<br>* 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<br>Biological: Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein),<br>* 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<br>|
| Experimental: Prime BBIBP-CorV, Boost BBIBP-CorV (A2)<br>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)<br>* 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<br>|
| Experimental: Prime Ad26.COV2.S, Boost BBIBP-CorV (B1)<br>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)<br>* 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<br>Biological: Ad26.COV2.S (Recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein),<br>* 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<br>|
| Experimental: Prime Placebo, Boost Ad26.COV2.S (B2)<br>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),<br>* 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<br>Biological: Placebo - Normal saline (0.9% sodium chloride solution)<br>* Placebo - Normal saline (0.9% sodium chloride solution) Dose formulation: Not Applicable Mode of administration: Intramuscular Storage conditions: 15°C to 30°C<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) and Geometric Mean Fold Rise (GMFR) | 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 | Till 12 months follow-up visit | 
| Geometric Mean Titers (GMTs) and Geometric Mean Fold Rise (GMFR) | GMTs of anti-SARS-CoV-2 anti-spike IgG as measured by immunoassay, 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 immunoassay, 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 immunoassay, 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 | Till 12 months follow-up visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, Vaccines, Mix and Match Trial