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.

Time frame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)

Population: Per-protocol efficacy (PP) set: participants in FAS who received 2 doses of DB study vaccine, were PCR negative at time of first vaccination, were seronegative at time of first vaccination and at 14 days after second vaccination and had no other major protocol deviations to possibly impact efficacy of vaccine before unblinding. Participants who had a positive PCR test between Day 1 and Day 70 and participants who discontinued prior to 14 days post-dose 2 were excluded.

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.

Time frame: From Day 1 up to end of double blind phase (7.2 months)

Population: FAS post dose 1 population included FAS participants excluding the participants who received a COVID-19 vaccination outside of the study prior to first study vaccination.

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.

Time frame: From Day 71 up to end of the COVID-19 episode (up to 90 days)

Population: PP set: participants in FAS who received 2 doses of double-blind study vaccine, were PCR negative at the time of first vaccination, were seronegative at the time of first vaccination and at 14 days after second vaccination and had no other major protocol deviations to possibly impact efficacy of vaccine before unblinding. 'N' (overall number of participants analyzed) = participants evaluable for this outcome measure.

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.

Time frame: From Day 1 up to end of double blind phase (7.2 months)

Population: FAS post dose 1 population included FAS participants excluding the participants who received a COVID-19 vaccination outside of the study prior to first study vaccination.

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

Time frame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)

Population: PP set: participants in FAS who received 2 doses of DB study vaccine, were PCR negative at time of first vaccination, were seronegative at time of first vaccination and at 14 days after second vaccination and had no other major protocol deviations to possibly impact efficacy of vaccine before unblinding. Participants who had a positive PCR test between Day 1 and Day 70 and participants who discontinued prior to 14 days post-dose 2 were excluded.

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.

Time frame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)

Population: PP set: participants in FAS who received 2 doses of DB study vaccine, were PCR negative at time of first vaccination, were seronegative at time of first vaccination and at 14 days after second vaccination and had no other major protocol deviations to possibly impact efficacy of vaccine before unblinding. Participants who had a positive PCR test between Day 1 and Day 70 and participants who discontinued prior to 14 days post-dose 2 were excluded.

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.

Time frame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)

Population: PP set: participants in FAS who received 2 doses of DB study vaccine, were PCR negative at time of first vaccination, were seronegative at time of first vaccination and at 14 days after second vaccination and had no other major protocol deviations to possibly impact efficacy of vaccine before unblinding. Participants who had a positive PCR test between Day 1 and Day 70 and participants who discontinued prior to 14 days post-dose 2 were excluded.

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.

Time frame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)

Population: PP set: participants in FAS who received 2 doses of DB study vaccine, were PCR negative at time of first vaccination, were seronegative at time of first vaccination and at 14 days after second vaccination and had no other major protocol deviations to possibly impact efficacy of vaccine before unblinding. Participants who had a positive PCR test between Day 1 and Day 70 and participants who discontinued prior to 14 days post-dose 2 were excluded.

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.

Time frame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)

Population: PP set: participants in FAS who received 2 doses of DB study vaccine, were PCR negative at time of first vaccination, were seronegative at time of first vaccination and at 14 days after second vaccination and had no other major protocol deviations to possibly impact efficacy of vaccine before unblinding. Participants who had a positive PCR test between Day 1 and Day 70 and participants who discontinued prior to 14 days post-dose 2 were excluded.

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.

Time frame: From at least 1 day after first vaccination on Day 1 (Day 2) up to end of double blind phase (7.2 months)

Population: Full analysis seronegative set included all randomized participants with at least 1 documented study vaccine administration, regardless of protocol deviations and who were seronegative at baseline.

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.

Time frame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)

Population: PP set: included participants of the FAS who received 2 doses of DB study vaccine, regardless of their serostatus at time of first vaccination and at 14 days after second vaccination, were PCR negative at time of first vaccination and had no other major protocol deviations to possibly impact efficacy of vaccine before unblinding. Participants who had a positive PCR test between Day 1 and Day 70 and participants who discontinued prior to 14 days post-dose 2 were excluded.

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.

Time frame: From at least 1 day after first vaccination on Day 1 (Day 2) up to end of double blind phase (7.2 months)

Population: Full analysis set (FAS) included all randomized participants with at least 1 documented study vaccine administration, regardless of protocol deviations and serostatus at enrollment.

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.

Time frame: From at least 14 days after first vaccination on Day 1 (Day 15) up to end of double blind phase (7.2 months)

Population: Per-protocol first dose efficacy (PPFD) population: Participants in FAS who received at least first dose of study vaccine in the double-blind phase and who were PCR negative at the time of first vaccination, who were not seropositive at baseline and who had no major protocol deviations before unblinding that were judged to possibly impact the efficacy of the vaccine. Participants who had a positive PCR test between Days 1 and 14 and participants who discontinued prior to Day 15 were excluded.

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.

Time frame: From at least 28 days after the first vaccination on Day 1 (Day 29) up to end of double blind phase (7.2 months)

Population: PPFD population: Participants in FAS who received at least first dose of study vaccine in the double-blind phase and who were PCR negative at the time of first vaccination, who were not seropositive at baseline and who had no major protocol deviations before unblinding that were judged to possibly impact the efficacy of the vaccine. Participants who had a positive PCR test between Day 1 and Day 28 and participants who discontinued prior to Day 29 were excluded.

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.

Time frame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)

Population: PP set: participants in FAS who received 2 doses of DB study vaccine, were PCR negative at time of first vaccination, were seronegative at time of first vaccination and at 14 days after second vaccination and had no other major protocol deviations to possibly impact efficacy of vaccine before unblinding. Participants who had a positive PCR test between Day 1 and Day 70 and participants who discontinued prior to 14 days post-dose 2 were excluded.

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.

Time frame: From Day 1 up to 7.2 months

Population: FAS post dose 1 population included FAS participants excluding the participants who received a COVID-19 vaccination outside of the study prior to first study vaccination.

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.

Time frame: From Day 1 up to end of double blind phase (7.2 months)

Population: FAS post dose 1 population included FAS participants excluding the participants who received a COVID-19 vaccination outside of the study prior to first study vaccination.

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.

Time frame: From Day 71 up to unblinding visit (7.2 months)

Population: PP set: participants in FAS who received 2 doses of DB study vaccine, were PCR negative at time of first vaccination, were seronegative at time of first vaccination and at 14 days after second vaccination and had no other major protocol deviations to possibly impact efficacy of vaccine before unblinding. Participants who had a positive PCR test between Day 1 and Day 70 and participants who discontinued prior to 14 days post-dose 2 were excluded.

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).

Time frame: 7 days after first vaccination on Day 1 (up to Day 8), 7 days after second vaccination on Day 57 (up to Day 64)

Population: Safety population was a subset of FAS for analyzing solicited local AEs. 'N' (overall number of participants analyzed) = participants evaluable for this outcome; 'n' (number analyzed) = participants evaluable at specific time points. N=0 in 'DB: Non-FAS Post-Dose 1: Placebo' arm, as no participant was evaluable in the FAS subset of this arm. n=0 in 'DB: Non-FAS Post-Dose 1' arm signifies the time point was not applicable since the participant did not receive a second vaccination.

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.

Time frame: 7 days after first vaccination on Day 1 (up to Day 8), 7 days after second vaccination on Day 57 (up to Day 64)

Population: Safety population was subset of FAS for analysis of solicited systemic AEs. 'N' (overall number of participants analyzed)=participants evaluable for this outcome measure; 'n' (number analyzed)= participants evaluable at specified time points. N=0 in 'DB: Non-FAS Post-Dose 1: Placebo' arm, as no participant was evaluable in the FAS subset of this arm. n=0 in 'DB: Non-FAS Post-Dose 1' arm signifies the time point was not applicable since the participant did not receive a second vaccination.

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.

Time frame: 28 days after first vaccination on Day 1 (up to Day 29), 28 days after second vaccination on Day 57 (up to Day 85)

Population: Safety population was subset of FAS for analysis of unsolicited AEs. 'N' (overall number of participants analyzed) = participants evaluable for this outcome measure; 'n' (number analyzed) = participants evaluable at specified time points. N=0 in 'DB: Non-FAS Post-Dose 1: Placebo' arm, as no participant was evaluable in the FAS subset of this arm. n=0 in 'DB: Non-FAS Post-Dose 1' arm signifies the time point was not applicable since the participant did not receive a second vaccination.

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).

Time frame: At Baseline (Day 1), Days 29, 57 and 71

Population: Per protocol immunogenicity (PPI) set: all randomized and vaccinated participants (received both vaccines in DB phase, including those who were part of immunogenicity subset and for whom immunogenicity data were available, excluding participants with major protocol deviations expected to impact immunogenicity outcomes. N (overall number of participants analyzed) = participants evaluated for this outcome measure, n (number analyzed) = number of participants evaluable at specified time points.