Covid-19 Living Data

Trial NCT04955626
Publication Barda N, Clin. Microbiol. Infect., 2023
Dates: 2022-03-23 to 2022-05-03
Funding: Private (BioNTech and Pfizer)
Conflict of interest: Yes

Methods
	RCT
	Location : Single center / Israel Follow-up duration (months): 3
	BNT162b2 30 mcg = (n=22) BNT162b2 60 mcg = (n=20) BNT162b2-Omi.BA.1/ 30 mcg = (n=20) BNT162b2-Omi.BA.1/ 60 mcg = (n=20) BNT162b2/15 mcg + BNT162b2-Omi.BA.1/15 mcg = (n=20) BNT162b2/30 mcg + BNT162b2-Omi.BA.1/30 mcg = (n=21)
Inclusion criteria	Participants who received three prior doses of 30ug BNT162b2 with the third dose being ≥4 months before day 1 of the study (visit 1) Age and Sex: Male or female participants ≥60 years of age Participants who are willing and able to comply with all scheduled visits and procedures Generally healthy participants, including healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the six weeks before enrollment, can be included Informed Consent: Capable of giving personal signed informed consent.
Exclusion criteria	Other medical or psychiatric conditions, including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of the study participation History of severe adverse reaction associated with a vaccine and/or severe allergic reaction to any component of the study intervention. Previous clinical COVID-19 (based on symptoms/signs history, or SARS-CoV-2 polymerase chain reaction (NAAT) result. Diagnosis of COVID-19 or positive antigen test for SARS-CoV-2 at baseline. Immunocompromised individuals with known or suspected immunodeficiency as determined by history and/or laboratory/physical examination. Bleeding diathesis or conditions associated with prolonged bleeding which could be a contraindication for intramuscular injection.Individuals who receive treatment with radiotherapy or immunosuppressive therapy including cytotoxic agents or systemic corticosteroids (if administered for >14 days at dose >20mg/day of prednisone or equivalent), e.g., for cancer or an autoimmune disease, or planned receipt throughout the study. Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention. Clinical Study Experience: Prior receipt of any COVID-19 vaccine other than BNT162b2. Investigator site staff or Pfizer-BNT employees directly involved in the conduct of the study. Receipt of medications intended to prevent COVID-19. Participation in other studies involving study intervention within 28 days prior to study entry and including 28 days after the dose of study intervention. Non-Pfizer interventional studies for prevention of COVID-19, which were prohibited throughout study participation.
Interventions
	Intervention 1 dose of BNT162b2 60mcg at least 4 months after 3rd shot of BNT162b2 1 dose of BNT161b2-OMI 30mcg at least 4 months after 3rd shot of BNT162b2 1 dose of BNT161b2-OMI 60mcg at least 4 months after 3rd shot of BNT162b2 1 dose of BNT161b2-OMI 15/15mcg at least 4 months after 3rd shot of BNT162b2 1 dose of BNT161b2-OMI 30/30mcg at least 4 months after 3rd shot of BNT162b2
	Control 1 dose of BNT161b2 30mcg at least 4 months after 3rd shot of BNT162b2
Participants
	Randomized 123 participants
	Characteristics of participants Type of participants: Adults N=123 61 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR
	Description of participants Healthy adults, age 60 years old or more and SARS-CoV-2 infection-free, in a single center in Israel
Primary outcome
	In the register Percentage of participants reporting local reactions [ Time Frame: For 7 days following the study vaccination ] Pain at the injection site, redness, and swelling as self-reported on electronic diaries.; Percentage of participants reporting systemic events [ Time Frame: For 7 days following the study vaccination ] Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.; Percentage of participants reporting adverse events [ Time Frame: from the study vaccination through 1 month after the study vaccination ] As elicited by investigational site staff; Percentage of participants reporting serious adverse events [ Time Frame: from the study vaccination through 6 months after the study vaccination ] As elicited by investigational site staff; To describe the immune response to BNT162b2 (30 µg or 60 µg), BNT162b2 OMI (30 µg or 60 µg), and a combination of BNT162b2 and BNT162b2 OMI (30 µg or 60 µg) given as a fourth dose in BNT162b2-experienced participants [ Time Frame: At each time point ] GMT of Omicron and reference-strain neutralizing titers GMFRs of Omicron and reference-strain neutralizing titers from before the study vaccination to subsequent time points Percentages of participants with seroresponse for Omicron and reference-strain neutralizing titers at each time point GMRs of Omicron and reference-strain neutralizing titers at each time point after the study vaccination between different vaccine groups
	In the report The neutralization titers of SARS-CoV-2 ancestral strain and the BA.1 variant of concern.
Documents available	Protocol NR Statistical plan * Data-sharing stated: No Data accessibility: gili.regev@sheba.health.gov.il (G. Regev-Yochay)
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to all available versions of the published article the study registry and supplemental material were used in data extraction and risk of bias assessment. The target sample size specified (n=180) was not achieved as recruitment was slower than expected. Some safety outcomes pre-specified in the registry were not reported in the paper. This trial is a pre-specified sub-study of a larger study.The article presented interim analyses for a study with ongoing follow-up.There were no important differences between registry and published report in population, procedures, interventions