Clinical trial NCT04984408: Efficacy, Immunogenicity and Safety of BBIBP-CorV Vaccine Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.
Official title: A Phase 3, Randomized, Observer-blind, Controlled Trial to Assess the Efficacy, Immunogenicity and Safety of BBIBP-CorV Vaccine Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: COVID-19 Disease
Lead sponsor: International Vaccine Institute
Sponsor class: OTHER
First posted: 2021-07-30
Enrollment: 8825
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, observer-blind, controlled, phase 3 trial will be conducted to assess the safety, immunogenicity and efficacy of two doses of intramuscular BBIBP-CorV vaccine, followed by a booster dose, in adults 18 years of age and older.
Primary purpose: PREVENTION

Brief summary: To expand the access and delivery of COVID-19 Vaccines in Africa (ECOVA), the investigators will conduct a phase 3, individually randomized, observer-blind, controlled (influenza vaccine) trial to evaluate the safety and efficacy of the BBIBP-CorV vaccine against any severe acute respiratory syndrome 2 (SARS-CoV- 2) infection among adults 18 years and older. The BBIBP-CorV vaccine is an inactivated SARS-CoV-2 vaccine (Vero cell) manufactured by the Beijing Institute of Biological Products (BIBP), China National Biotec Group (CNBG), Sinopharm, Beijing, People's Republic of China and received emergency use authorization (EUA) from World Health Organization (WHO).

Detailed description: The investigators will conduct a randomized, observer-blind, controlled, phase 3 trial will be conducted to assess the safety, immunogenicity and efficacy of two doses of intramuscular BBIBP-CorV vaccine, followed by a booster dose, in adults 18 years of age and older. . Study Arms 1 and 2 will have two groups: group 1 - HIV-uninfected receiving BBIBP-CorV or Flu Quadrivalent; group 2 - HIV-infected receiving BBIBP-CorV or Flu Quadrivalent. Arm 3 will have 1 group - HIV-uninfected co-administration group receiving both vaccines. The randomization will be stratified by HIV status. Active surveillance for covid-19 will be carried out and immunogenicity will be assessed for a subset of population.

Eligibility criteria: Inclusion Criteria:

* Female and male adults aged 18 years and older (Arm 1-Group 1 and Arm 2-Group 1) and 18-65 years (Arm 1 - Group 2, Arm 2-Group 2 and Arm3-Group1) at the time of consent.
* Residing within the Beira and Maputo health region and planning to stay for the study duration.
* HIV-negative test result at the day of screening for participants in Group 1, in Arms 1, 2 and 3
* HIV-positive and on anti-retroviral treatment for at least six months for participants in Group 2, in Arms 1 and 2
* 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 four weeks after the third vaccination.
* Able and willing to comply with all study requirements, based on the assessment of the investigator.
* Provide written informed consent before any trial procedure.

Exclusion Criteria:

* Pregnant, lactating, or with intention to become pregnant during the study.
* Planned receipt of any investigational vaccine than the study intervention within 28 days before and after each study vaccination.
* Active COVID-19 infection at the time of enrollment
* History of allergic reactions or anaphylaxis to previous immunization or allergies to any components of the vaccines.
* History of bleeding disorder, or prior history of significant bleeding or bruising following intramuscular injections or venipuncture (for the immunogenicity subset and HIV infected participants).
* 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: Protection conferred by BBIBP-CorV vaccine against any COVID-19 disease
timeFrame: Up to two years follow up from the date of enrollment
Secondary outcomes:
measure: Incidence of solicited adverse events, unsolicited adverse events and serious adverse events and adverse events of special interest (AESIs)
timeFrame: local solicited adverse events within 7 days and systemic solicited adverse events within 14 days of each vaccination, unsolicited adverse events within 28 days of each vaccination
measure: Protection conferred by BBIBP-CorV vaccine against symptomatic COVID-19 disease
timeFrame: Till two years follow up from the date of enrollment
measure: Protection conferred by BBIBP-CorV vaccine against asymptomatic SARS-CoV-2 infection (any SARS-CoV-2 variant)
timeFrame: Till two years follow up from the date of enrollment
measure: Protection conferred by BBIBP-CorV vaccine against severe COVID-19 disease and COVID-19 associated death
timeFrame: Till two years follow up from the date of enrollment
measure: Geometric Mean Titers (GMT) and Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody in subset of participants
timeFrame: Till two years follow up from the date of enrollment
measure: Incidence of solicited adverse events, unsolicited adverse events and serious adverse events and adverse events of special interest (AESIs) in HIV-infected adults
timeFrame: Till two years follow up from the date of enrollment
measure: Geometric Mean Titers (GMT) and Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody in subset of participants in HIV-infected adults
timeFrame: Till two years follow up from the date of enrollment
measure: SARS-CoV-2 sequence variants among HIV-infected and HIV-uninfected, BBIBP-CorV vaccine and placebo recipients
timeFrame: Till two years follow up from the date of enrollment
measure: Geometric Mean Titers (GMT) and Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody in the Arm 3 as compared to Arm 1 and 2 (subset participants).
timeFrame: Till two years follow up from the date of enrollment
measure: Incidence of adverse event (AE) after each vaccination, serious adverse event (SAE), adverse events of special interests (AESIs) according to Brighton Collaboration list for COVID-19 vaccine studies among participants receiving the study vaccines.
timeFrame: Till two years follow up from the date of enrollment
measure: Humoral and cellular immune responses of HIV-infected participants as compared to HIV-uninfected vaccine and control arms (subset participants of Arms 1 and 2)
timeFrame: Till two years follow up from the date of enrollment
measure: Geometric Mean Titers (GMT) and Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody following booster dose of BBIBP-CorV vaccine
timeFrame: Till two years follow up from the date of enrollment
measure: Incidence of solicited adverse events, unsolicited adverse events and serious adverse events and adverse events of special interest (AESIs) among HIV uninfected adults.
timeFrame: Till two years follow up from the date of enrollment
Other outcomes:
measure: Acute phase reactants in COVID-19 patients that best predict COVID-19 disease and, hence, the control of protection against COVID-19 infection.
timeFrame: Till two years follow up from the date of enrollment
measure: Profile of the epitope-specific humoral immune response that tracks with protective immunity following natural infection or vaccine-induced immunity, using Systems Serology
timeFrame: Till two years follow up from the date of enrollment
measure: Any pregnancy outcomes after immunization in the intervention arm(s) as compared to control arm(s).
timeFrame: Till two years follow up from the date of enrollment
measure: The medical and psychological outcomes of COVID-19 patients in the first two years of follow-up
timeFrame: Till two years follow up from the date of enrollment
measure: Identify novel SARS-CoV-2 host targets and host-virus interactions in low- and middle-income countries (LMIC) participants.
timeFrame: Till two years follow up from the date of enrollment
Locations:
Study officials:
affiliation: International Vaccine Institute
name: Florian Marks, PhD
role: PRINCIPAL_INVESTIGATOR
References: