A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults

Molecularly confirmed moderate to severe/critical COVID-19 was defined as a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive reverse transcription/polymerase chain reaction (RT-PCR) or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Moderate included one sign or symptom such as respiratory rate >=20 breaths per minute (min) and symptoms such as shortness of breath or two signs or symptoms such as heart rate >=90 beats/min and symptoms such as cough from a list of signs and symptoms and severe/critical included one of the following signs and symptoms: respiratory rate >=30 breaths/min, heart rate >=125 beats/min, oxygen saturation (SpO2) <=93 percent (%) on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to Intensive Care Unit (ICU), death defined as per FDA guidance.

Molecularly confirmed moderate to severe/critical COVID-19 was defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Moderate included one sign or symptom such as respiratory rate greater than or equal to (>=) 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms such as heart rate >= 90 beats per min and symptoms such as cough from a list of signs and symptoms and severe/critical included one of the following signs and symptoms: respiratory rate >=30 breaths/minute, heart rate >=125 beats/minute, SpO2 less than or equal to (<=) 93% on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to the ICU, death defined as per US Food and Drug Administration (FDA) guidance.

Molecularly confirmed moderate to severe/critical COVID-19 was defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Moderate included one sign or symptom such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms such as heart rate >= 90 beats per min and symptoms such as cough from a list of signs and symptoms and severe/critical included one of the following signs and symptoms: respiratory rate >=30 breaths/minute, heart rate >=125 beats/minute, SpO2 <= 93% on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to the ICU, death defined as per FDA guidance.

Molecularly confirmed moderate to severe/critical COVID-19 was defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Moderate included one sign or symptom such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms such as heart rate >= 90 beats per min and symptoms such as cough from a list of signs and symptoms and severe/critical included one of the following signs and symptoms: respiratory rate >=30 breaths/minute, heart rate >=125 beats/minute, SpO2 <= 93% on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to the ICU, death defined as per FDA guidance.

Molecularly confirmed moderate to severe/critical COVID-19 was defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Moderate included one sign or symptom such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms such as heart rate >= 90 beats per min and symptoms such as cough from a list of signs and symptoms and severe/critical included one of the following signs and symptoms: respiratory rate >=30 breaths/minute, heart rate >=125 beats/minute, SpO2 <= 93% on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to the ICU, death defined as per FDA guidance.

Molecularly confirmed moderate to severe/critical COVID-19 was defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Moderate included one sign or symptom such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms such as heart rate >= 90 beats per min and symptoms such as cough from a list of signs and symptoms and severe/critical included one of the following signs and symptoms: respiratory rate >=30 breaths/minute, heart rate >=125 beats/minute, SpO2 <= 93% on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to the ICU, death defined as per FDA guidance.

Number of participants with first occurrence of COVID-19 requiring medical intervention (such as a composite endpoint of hospitalization, ICU admission, mechanical ventilation, and extracorporeal membrane oxygenation [ECMO]), linked to objective measures such as decreased oxygenation, X-ray or computed tomography [CT] findings and linked to any molecularly confirmed, COVID-19 with onset at least 14 days post second vaccination were reported.

AUC of SARS-CoV-2 viral load was assessed in confirmed COVID-19 cases using RT-PCR. Nasal swabs were used to detect and/or quantify SARS-CoV-2. Due to change in the planned analysis, data was collected and analyzed for participants with molecularly confirmed symptomatic COVID-19 regardless of severity that is mild, moderate or severe and was not collected and analyzed separately for moderate to severe cases.

Molecularly confirmed mild Covid-19 was defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample and one of the following signs and symptoms: fever (>=38 degree Celsius or >=100.4 degree Fahrenheit), sore throat, malaise (loss of appetite, generally unwell, fatigue, physical weakness), headache, muscle pain (myalgia), gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, chills, new or changing olfactory or taste disorders, red or bruised looking feet or toes, or shaking chills or rigors.

Molecularly confirmed COVID-19 was defined as SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample; and COVID-19 symptoms consistent with those defined by the US FDA harmonized case definition at the time of finalization of the study protocol: 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, and diarrhea.

BOD is a weighted version of the mild, moderate, and severe/critical vaccine efficacies and was evaluated based on the first occurrence of molecularly confirmed COVID-19, including mild, moderate or severe/critical COVID-19 case.

Number of participants with serologic conversion between Day 71 up to unblinding visit using an ELISA were reported. Due to change in planned analysis, data was collected and analyzed between Day 71 up to unblinding visit instead of from baseline to unblinding visit.

Number of participants with asymptomatic infection detected by RT-PCR with onset at least 14 days after the second vaccination (Day 71) were reported.

Number of participants with first occurrence of SARS-CoV-2 infection (serologically and/or molecularly confirmed) with onset at least 14 days after the second vaccination (Day 71) were reported.

An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product that does not necessarily have a causal relationship with the vaccine. SAE was any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

Number of participants with AESIs were reported. AESIs were significant AEs that were judged to be of special interest because of clinical importance, known or suspected class effects, or based on nonclinical signals. Thrombosis with Thrombocytopenia Syndrome (TTS), a syndrome characterized by a combination of both a thrombotic event and thrombocytopenia, was considered to be an AESI in this study. A suspected TTS case was defined as: Thrombotic events: suspected deep vessel venous or arterial thrombotic events; Thrombocytopenia, defined as platelet count below 150,000/micro liter.

An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product that does not necessarily have a causal relationship with the vaccine. MAAEs were defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason.

An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product that does not necessarily have a causal relationship with the vaccine. MAAEs were defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason.

An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product that does not necessarily have a causal relationship with the vaccine. Participants who were enrolled in safety subset (SS) were asked to note in the e-Diary occurrences of injection site pain/tenderness, erythema, and swelling at the study vaccine injection site daily for 7 days post each vaccination (day of vaccination and the subsequent 7 days).

An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product that does not necessarily have a causal relationship with the vaccine. Participants who were enrolled in safety subset were instructed on how to record daily temperature using a thermometer provided for home use. Participants recorded temperature in e-Diary in evening of the day of vaccination, and then daily for next 7 days approximately at same time each day. If more than 1 measurement was made on any given day, the highest temperature of that day was recorded in e-Diary. Fever was defined as endogenous elevation of body temperature >= 38.0 degree Celsius or >=100.4-degree Fahrenheit, as recorded in at least 1 measurement. Participants also noted the signs and symptoms in e-Diary on a daily basis for 7 days post each vaccination (day of vaccination and subsequent 7 days), for the following events: fatigue, headache, nausea, myalgia.

An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product that does not necessarily have a causal relationship with the vaccine. Unsolicited AEs were all AEs for which the participant is not specifically questioned in the participant diary.

Binding antibodies to SARS-CoV-2 S protein as assessed by ELISA to measure humoral immune response was reported. The lower limit of quantification (LLOQ) was 50.3 ELISA units per milliliter (EU/mL). A sample was considered positive if the value was strictly greater than the LLOQ (>LLOQ).