Clinical trial NCT04998240: Mix and Match Heterologous Prime-Boost Study Using Approved COVID-19 Vaccines
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 and Madagascar.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Covid19
Keywords: SARS-CoV-2, Vaccines, Mix and Match Trial
Lead sponsor: International Vaccine Institute
Sponsor class: OTHER
Collaborators: name: The Coalition for Epidemic Preparedness Innovations (CEPI)
name: Instituto Nacional de Saúde, Mozambique
name: University of Antananarivo
name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Harvard University
name: Heidelberg University
First posted: 2021-08-10
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Geometric Mean Titers (GMTs) of anti-SARS-CoV-2 neutralizing antibodies
timeFrame: Four Weeks after second dose
measure: Incidence of SAEs and AESI observed at any time point during the entire study period
timeFrame: Till 12 months follow-up visit
measure: Incidence of solicited reactions within 7 days (local reactions) and 14 days (systemic reactions)
timeFrame: Within 7 days (local reactions) and 14 days (systemic reactions) following each vaccination
measure: Incidence of unsolicited adverse events that are within 28 days after each vaccination
timeFrame: Within 28 days after each vaccination
measure: Incidence of changes in laboratory safety measures from baseline to day 28 after each vaccination
timeFrame: Within 28 days after each vaccination
Secondary outcomes:
measure: Geometric Mean Titers (GMTs) and Geometric Mean Fold Rise (GMFR)
timeFrame: Till 12 months follow-up visit
measure: Geometric Mean Titers (GMTs) and Geometric Mean Fold Rise (GMFR)
timeFrame: Till 12 months follow-up visit
Other outcomes:
measure: Cellular immune responses against SARS-CoV-2
timeFrame: Till 12 months follow-up visit
measure: GMTs, GMFR from baseline
timeFrame: Till 12 months follow-up visit
measure: Genome sequencing of SARS-CoV-2 viruses isolated post prime or booster dose
timeFrame: After diagnosis of SARS-CoV-2 infection
measure: Profile of vaccine-induced humoral response against SARS-CoV-2
timeFrame: Till 12 months follow-up visit
Locations:
city: Antananarivo
country: Madagascar
facility: Madagascar Institute for Vaccine Research (MIVR), University of Antananarivo
city: Maputo
country: Mozambique
facility: Centro de Investigação e Treino em Saúde da Polana Caniço - Instituto Nacional de Saúde
Study officials:
affiliation: International Vaccine Institute
name: Florian Marks, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Nacional de Saúde, Mozambique
name: Ilesh Jani, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Madagascar Institute for Vaccine Research (MIVR), University of Antananarivo
name: Raphael Rakotozandrindrainy, MD
role: PRINCIPAL_INVESTIGATOR
References: