Covid-19 Living Data

Trial NCT05289037
Publication Branche A, Clin. Infect. Dis., 2023
Dates: 2022-10-04 to 2022-10-28
Funding: Public/non profit (National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute (NCI), Infectious Diseases Clinical Research Consortium. (IDCRC); National Institutes of Health (NIH))
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / USA Follow-up duration (months): 1
	BNT162b2 Wildtype/Omicron BA.1 (n=101) BNT162b2 Omicron BA.4/5 (n=101)
Inclusion criteria	Healthy adults >= 18-49 years with or without a history of prior SARS-CoV-2 infection confirmed receipt of a complete primary and booster COVID-19 vaccine series, either homologous or heterologous, with an FDA authorized/approved vaccine at least 16 weeks prior to study vaccine dose 1 Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests and other study procedures Determined by medical history, targeted physical examination and clinical judgement of the investigator to be in stable state of health Note: Participants with pre-existing stable chronic medical conditions defined as condition not requiring significant change in therapy or hospitalization for worsening disease within 4 weeks from enrollment, can be included at the discretion of the investigator.
Exclusion criteria	Confirmed SARS-CoV-2 infection < 16 weeks prior to any study vaccine dose Pregnant and breastfeeding participants Prior administration of an investigational coronavirus vaccine at any time or SARS-CoV-2 immunoglobulin, monoclonal antibody or plasma antibody therapy in the preceding 3 months Note: subjects that participated in clinical trials of products that are now FDA approved/authorized are allowed to participate Current/planned simultaneous participation in another interventional study or receipt of any investigational study product within 28 days prior to vaccine study dose(s) A history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine, polyethylene glycol (PEG), polysorbate or nanolipid particles A history of myocarditis or pericarditis at any time prior to enrollment (for subjects in stages 1, 2 and 4) Received or plans to receive a vaccine within 28 days prior to or after any dose of study vaccine. Note: Receipt of seasonal influenza vaccine is allowed at any time Bleeding disorder diagnosed by a healthcare provider (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or bleeding difficulties with intramuscular injections or blood draws Current or previous diagnosis of an immunocompromising condition or other immunosuppressive condition Advanced liver or kidney diseases Advanced (CD4 count < 200) and/or untreated HIV, untreated Hepatitis B or untreated Hepatitis C Received oral, intramuscular or intravenous systemic immunosuppressants, or immune-modifying drugs for >14 days in total within 6 months prior to any study vaccine dose (for corticosteroids = 20 mg > / = day of prednisone equivalent). Note: Topical medications are allowed Received immunoglobulin or blood-derived products, within 3 months prior any study vaccine dose Received chemotherapy, immunotherapy or radiation therapy within 6 months prior to any study vaccine dose Study personnel or an immediate family member or household member of study personnel Is acutely ill or febrile 72 hours prior to or at vaccine dosing (fever defined as > / = 38.0 degrees Celsius/100.4 degrees Fahrenheit). Participants meeting this criterion may be rescheduled within the relevant window periods. Note: Afebrile participants with minor illnesses can be enrolled at the discretion of the Investigator, as long as the illness is not suggestive of COVID-19 Plan to receive a COVID-19 booster vaccine outside of the study within the next 180 days (for subjects in Stage 4 only).
Interventions
	Intervention 1 IM dose of 30 mcg BNT162b2 bivalent Wildtype/Omicron BA.1 (2nd booster), at least 16 weeks following 1st boost+primary series with any FDA authorized COVID-19 vaccines.
	Control 1 IM dose of 30 mcg BNT162b2 bivalent Wildtype/Omicron BA.4/5 (2nd booster), at least 16 weeks following 1st boost+primary series with any FDA authorized COVID-19 vaccines.
Participants
	Randomized 202 participants
	Characteristics of participants Type of participants: Adults including healthy or stable co-morbidities N=202 88 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 18-49
	Description of participants Adults 18-49 who are healthy or have stable co-morbidities in 20 centres in the USA.
Primary outcome
	In the register 1) Change from baseline in Geometric Mean Fold Rise (GMFR) [ Time Frame: Day 1 through Day 366 ] As measured by Immunoglobin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) or Multiplex Meso Scale Discovery (MSD) antibody binding assays to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Neutralization titers will be calculated by neutralization assays using SARS-CoV-2 variant-specific S-pseudotyped viruses and different strains of live SARS-CoV-2. 2) Change from baseline in Geometric Mean Titers (GMT) [ Time Frame: Day 1 through Day 366 ] As measured by Immunoglobin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) or Multiplex Meso Scale Discovery (MSD) antibody binding assays to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Neutralization titers will be calculated by neutralization assays using SARS-CoV-2 variant-specific S-pseudotyped viruses and different strains of live SARS-CoV-2. 3) Change in Geometric Mean Ratio [ Time Frame: Day 1 through Day 366 ] As measured by Immunoglobin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) or Multiplex Meso Scale Discovery (MSD) antibody binding assays to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Neutralization titers will be calculated by neutralization assays using SARS-CoV-2 variant-specific S-pseudotyped viruses and different strains of live SARS-CoV-2
	In the report Evaluate the magnitude and breadth of SARS-CoV-2 specific antibody titers in serum samples by estimating 95% confidence intervals (CI) for the geometric mean titer (GMT) at each timepoint when samples are collected.
Documents available	Protocol NR Statistical plan * Data-sharing stated: Yes Data accessibility: Dr. Angela Branche, angela.branche@urmc.rochester.edu
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 the pre-print article, the study registry was used in data extraction and risk of bias assessment. The protocol, statistical analysis plan and supplementary appendix were not available. This was a brief report of preliminary results for a study with on-going follow up. Adverse events were reported in the registry, but not in the paper. Only immunologic results are reported, up to 28 days (after 2nd boost); adverse events are not reported. There is no change from the trial registration in the intervention and control treatments. The target sample size (n=200) specified in the registry was achieved (n=202). This trial was updated on May 2nd 2023, after publication of the study report.