Trial Outcomes & Findings for Study of Monovalent and Bivalent Recombinant Protein Vaccines Against COVID-19 in Adults 18 Years of Age and Older (NCT NCT04904549)

The study was conducted at 87 centers in 11 countries from 26 May 2021 to 31 August 2024.

10139 participants were enrolled in Stage 1 and 13531 in Stage 2. A total of 23670 unique participants were enrolled in the study. Participants from the Original Cohort (Stage 1 and Stage 2) were included in the booster cohort because these assessed separate objectives. The study was terminated as per Sponsor decision.

Study of Monovalent and Bivalent Recombinant Protein Vaccines Against COVID-19 in Adults 18 Years of Age and Older

Symptomatic COVID-19 was defined as virologically-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness (CLI).

A solicited reaction was defined as an "expected" adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and case report form (CRF) collected within 7 days after each injection and considered to be related to the corresponding study vaccine administered. An injection site reaction was an AR at and around the injection site of the study vaccine. Systemic AR were all ARs that were not injection site reactions and included systemic manifestations such as headache, fever, as well as localized or topical manifestations that are not associated with the injection site.

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, that was pre-listed in the CRF in terms of diagnosis and onset window post-vaccination.

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Immediate events were recorded to capture medically relevant unsolicited injection site and systemic AEs which occurred within the first 30 minutes after vaccination.

An SAE was defined as any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An AESI (serious or non-serious) was 1 of scientific and medical concern specific to the Sponsor's study intervention or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor could be appropriate. An MAAE was a new onset or a worsening of a condition that prompted the participant or participant's parent/guardian to seek unplanned medical advice at a physician's office or Emergency Department.

Virologically-confirmed SARS-CoV-2 infection was defined as a positive result for SARS CoV-2 by nucleic acid amplification test (NAAT) on at least 1 respiratory sample. This included positive results by any NAAT that included tests performed outside the trial protocol if confirmed by the adjudication committee. Symptomatic COVID-19 was defined as virologically-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness. Percentages are rounded off to the tenth decimal place. Here, percentage of participants with virologically-confirmed SARS-CoV-2 infection and/or symptomatic COVID-19 (regardless of adjudication) are reported.

SARS-CoV-2 infection was defined as a serologically-confirmed SARS-CoV-2 infection or virologically-confirmed SARS-CoV-2 infection.

Severe COVID-19 was defined as COVID-19 with any 1 of the following: Any clinical signs of severe illness measured at least on 2 occasions separated by 30 minutes. Supplemental oxygen administration for \> 1 hour. Use of invasive or non-invasive ventilation or extracorporeal membrane oxygenation. Clinical diagnosis of respiratory failure. Significant acute renal, hepatic, or neurologic dysfunction. Shock. Admission to an intensive care unit. Death.

Asymptomatic SARS-CoV-2 infection was defined as SARS-CoV-2 infection, with no reported COVID-19-like illness episodes between enrollment and 14 days after the timepoint at which SARS-CoV-2 infection was ascertained.

The viral copies were collected as protocol-defined respiratory swabs during participant's illness episode and reported as positive continuous values. Here, duration between two consecutive positive NAAT results was calculated as: (the date of last swab tested positive) - (the date of first tested positive) + 1.

Duration between two consecutive positive NAAT results was calculated as: the date of last swab tested positive - the date of first swab tested positive + 1.

Virologically-confirmed SARS-CoV-2 infection was defined as a positive result for SARS-CoV-2 by NAAT on at least 1 respiratory sample. Respiratory samples for NAAT testing were collected in participants with CLI through the study.

CDC-defined COVID-19 included virologically-confirmed SARS-CoV-2 infection with at least 1 of: fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea.

Hospitalized COVID-19 was defined as an episode of symptomatic COVID-19 that required inpatient hospitalization.

Symptomatic COVID-19 was defined as virologically-confirmed SARS-CoV-2 infection accompanied by protocol-defined CLI. Moderate COVID-19 was defined as symptomatic COVID-19 with either shortness of breath that persisted for at least 12 hours or clinical signs of moderate illness measured at least on 2 occasions separated by 30 minutes and no clinical signs indicative of severe COVID-19.

Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.

Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 strain was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.

Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 strain was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.

Responders are participants who had baseline values below lower limit of quantification (LLOQ) with quantifiable neutralization titer above assay LLOQ at each pre-defined post-vaccination timepoint and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination timepoint.

Responders are participants who had baseline values below LLOQ with quantifiable neutralization titer above assay LLOQ at each pre-defined post-vaccination timepoint and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination timepoint.

Responders are participants who had baseline values below LLOQ with quantifiable neutralization titer above assay LLOQ at each pre-defined post-vaccination timepoint and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination timepoint.

Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with serum neutralization assay (monogram assay). Participants with neutralization antibody titers \>=2-fold and \>=4-fold increase from baseline (pre-vaccination) are reported.

Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 strain was measured with serum neutralization assay (monogram assay). Participants with neutralization antibody titers \>=2-fold and \>=4-fold increase from baseline (pre-vaccination) are reported.

Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 strain was measured with serum neutralization assay (monogram assay). Participants with neutralization antibody titers \>=2-fold and \>=4-fold increase from baseline (pre-vaccination) are reported.

Symptomatic COVID-19 is defined as virologically-confirmed SARS-CoV-2 infection accompanied by protocol-defined CLI. Grade 1: A type of AE that was usually transient and required only minimal treatment or therapeutic intervention and did not generally interfere with usual activities of daily living. Grade 2: A type of AE that was usually alleviated with additional therapeutic intervention and interfered with usual activities of daily living, causing discomfort but posed no significant or permanent risk of harm to the research participant. Grade 3: A type of AE that interrupted usual activities of daily living, or significantly affects clinical status, or required intensive therapeutic intervention.

The COVID-19 severity scale was based on the 7-point ordinal scale of clinical assessments: 1: death; 2: hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 3: hospitalized, on non-invasive ventilation or high flow oxygen devices; 4: hospitalized, that required supplemental oxygen; 5: hospitalized, that did not require supplemental oxygen- discharged but required ongoing medical care (COVID-19 related or otherwise); 6: hospitalized, that did not require supplemental oxygen discharged without ongoing medical care; 7: not hospitalized.

Death associated with COVID-19 was defined as death in a participant with COVID-19 who died within 28 days of the first positive specimen date or who died more than 28 days after the first specimen date and COVID-19 was mentioned as an immediate or underlying cause of death on the death certificate.