A Single Heterologous Booster Vaccination Study of TAK-019 in Healthy Japanese Adults (COVID-19)

A Phase 3, Single Arm, Open-Label Trial to Evaluate the Immunogenicity and Safety of a Single Heterologous Booster Vaccination of TAK-019 in Healthy Japanese Male and Female Adults Aged 20 Years and Older (COVID-19)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05299359

Enrollment

150

Registered

2022-03-29

Start date

2022-04-15

Completion date

2023-10-18

Last updated

2024-10-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Coronavirus Disease (COVID-19)

Brief summary

TAK-019 is a vaccine in development to protect people against Covid-19. The main aims of the study are to learn if TAK-019 can protect people from Covid-19 and to check for side effects from TAK-019 for participants who will receive TAK-019 as heterologous booster vaccination. This study consists of two parts, main part and extension part. Firstly, participants who completed 2 doses primary vaccinations 6 to 12 months prior to the trial vaccination can take part in main study. At the first visit of main part of this study, the study doctor will check if each person can take part. Participants who can take part will receive an injection of TAK-019 as booster vaccination. Participants will be asked to record their temperature and any medical problems in an electronic diary for up to 7 days after the injection. During the main part, participants will visit the clinic for regular check-ups, blood tests, and sometimes for nose swab samples. When all participants have attended a clinic visit 28 days after the injection, the study sponsor (Takeda) will check how many participants have made enough antibodies to protect them against Covid-19. Participants who received the first single booster vaccination of TAK-019 in the main part and remained in study follow-up at least 5 months will be able to decide to take part in the extension part of this study. At the first visit of extension part of this study, the study doctor will check if each person can take part. Participants who can take part will receive an injection of TAK-019 as a second booster vaccination at the first visit of extension part. The participants will stay in the main part of this study for up to 12 months after they have had their injection or up to the start of extension part. For participants who will take part in the extension part, they will stay in the extension part for up to 12 months from the start of extension part. During this time, the doctors will continue to collect blood samples to check immune response. Also, they will check if participants have any more side effects from TAK-019.

Interventions

BIOLOGICALTAK-019

TAK-019 intramuscular injection

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

MAIN PART: 1. Healthy Japanese male and female adult participants aged \>= 20 years of age at the time of signing of informed consent. 2. Participant who completed 2 doses primary vaccinations with another specified mRNA vaccine which is available in Japan 6 to 12 months prior to the trial vaccination. EXTENSION PART: 3. Participants who received the first trial vaccination at least 5 months earlier and are currently enrolled in the Main Part (ie, not have withdrawn or discontinued early).

Exclusion criteria

MAIN PART: 1. Participants who received any other SARS-CoV-2 vaccine (except for the specified mRNA vaccine) or other experimental novel coronavirus vaccine prior to the trial. 2. Participant who received a booster vaccination (i.e. 3rd dose) 3. Participants who have close contact of anyone known to have COVID-19 within 14 days prior to the trial vaccination. 4. Participants who were tested positive for SARS-CoV-2 prior to the trial. 5. Participants who have traveled outside of Japan in the 30 days prior to the trial participation. 6. Participants with a clinically significant active infection or oral temperature \>= 38 degree Celsius within 3 days of the intended date of the first single booster vaccination. 7. Participants with body mass index (BMI) greater than or equal to 30 kg/m\^2 (BMI= weight in kg/ height in meters\^2) EXTENSION PART: 8. Participants with a clinically significant active infection or oral temperature \>=38 degree Celsius within 3 days of the intended date of the second single booster vaccination.

Design outcomes

Primary

Measure	Time frame	Description
Main Part: Percentage of Participants With Medically-Attended Adverse Events (MAAEs) Until Day 29	Main Part: Up to Day 29	MAAEs were defined as AEs leading to an unscheduled visit to or by a healthcare professional including visits to an emergency department, but not fulfilling seriousness criteria.
Main Part: Geometric Mean Titers (GMT) Ratio of Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Day 15 Compared With That Observed on Day 36 in Participants From the TAK-019-1501 Study	Day 15 for this study (14 days after the vaccination); Day 36 for TAK-019-1501 study (14 days after the second vaccination)	GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average for each group. Titer values was measured as below lower limit of quantification (LLOQ) were imputed to a value that was half of the LLOQ. LLOQ was equal to 20. GMT for each group and GMT ratio of neutralizing antibody titers to the ancestral strain (wild-type virus) on Day15 after a single booster vaccination (14 days after the booster vaccination) compared with that observed on Day 36 (14 days after the second vaccination) in participants from the TAK-019-1501 study (NCT04712110) were reported. GMT ratio was calculated with GMT of TAK-019-3001 on Day 15 divided by GMT of TAK-019-1501 study on Day 36. Here, ELISA is Enzyme-linked immunosorbent assay.
Main Part: Percentage of Participants With Reported Solicited Local Adverse Events (AEs) for 7 Days Following the First Single Booster Vaccination	Main Part: 7 days after the first single booster vaccination	AE was defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product (IMP); it did not necessarily have to have a causal relationship with IMP administration. Reported solicited local AEs were defined as injection site pain, tenderness, erythema/redness, induration, and swelling.
Main Part: Percentage of Participants With Solicited Systemic AEs for 7 Days Following the First Single Booster Vaccination	Main Part: 7 days after the first single booster vaccination	Solicited systemic AEs were defined as fever, fatigue, malaise, myalgia, arthralgia, nausea/vomiting, and headache.
Main Part: Percentage of Participants With Unsolicited AEs for 28 Days Following the First Single Booster Vaccination	Main Part: 28 days after the first single booster vaccination	Unsolicited AEs defines as other AEs than solicited local AEs and solicited systemic AEs.
Main Part: Percentage of Participants With Solicited and Unsolicited Serious Adverse Events (SAE) Until Day 29	Main Part: Up to Day 29	An SAE was defined as any untoward medical occurrence that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, or is an important medical event. Solicited SAEs and unsolicited SAEs were reported.
Main Part: Percentage of Participants With Adverse Event of Special Interest (AESI) Until Day 29	Main Part: Up to Day 29	An AESI was defined as AEs that will be specifically highlighted to the Investigator. AESIs for the study included the Potential Immune Mediated Medical Conditions (PIMMC) and AEs specific to COVID-19. PIMMC is categorized as following; neuroinflammatory disorders, musculoskeletal and connective tissue disorders, vasculitides, gastrointestinal disorders, hepatic disorders, renal disorders, cardiac disorders, skin disorder, hematologic disorders, metabolic disorders, and other disorders.
Main Part: Percentage of Participants With Any AE Leading to Withdrawal From the Trial Until Day 29	Main Part: Up to Day 29	Percentage of participants with any AE leading to withdrawal from the trial until Day 29 was reported.
Main Part: Percentage of Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection Until Day 29	Main Part: Up to Day 29	Percentage of participants with SARS-CoV-2 infection until Day 29 of the main part of the trial were reported in this outcome measure.

Secondary

Measure	Time frame	Description
Main Part: Percentage of Participants With Any AE Leading to Participant's Withdrawal From the Trial From the Day of the First Single Booster Vaccination Throughout the Main Part of Trial	Main Part: Day 1 up to Day 366	Percentage of participants with any AE leading to participant's withdrawal from the trial from the day of the first single booster vaccination throughout the main part of trial was reported.
Main Part: Percentage of Participants With SARS-CoV-2 Infection Throughout the Main Part of Trial	Main Part: Day 1 up to Day 366	Percentage of participants with SARS-CoV-2 infection throughout the main part of trial was reported.
Extension Part: GMT of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 15, 29, 91, 181, and 366	Extension Part: Day 15, 29, 91, 181, and 366	GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average. Titer values was measured as below LLOQ were imputed to a value that was half of the LLOQ. LLOQ was equal to 200 EU/mL.
Extension Part: GMFR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Extension Part Day 15, 29, 91, 181, and 366	Extension Part: Day 15, 29, 91, 181, and 366	The GMFR was calculated as the ratio of the post-second-booster-vaccination titer level to extension part baseline titer level. Where extension part baseline was defined as last measurement taken before the second booster vaccination.
Extension Part: Seroconversion Rate (SCR) of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Extension Part Day 15, 29, 91, 181, and 366	Extension Part: Day 15, 29, 91, 181, and 366	SCR was defined as percentage of participants with 4-fold or more rises in titer from extension part baseline. Where extension part baseline was defined as last measurement taken before the second booster vaccination.
Extension Part: GMT of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	Extension Part: Day 15, 29, 91, 181, and 366	The neutralization titer was expressed as the reciprocal of the highest dilution at \>= 50% of the replicate wells were protected from infection (MN50). GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average. Titer values was measured as below LLOQ were imputed to a value that was half of the LLOQ where LLOQ was equal to 20.
Extension Part: GMFR of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	Extension Part: Day 15, 29, 91, 181, and 366	The neutralization titer was expressed as the reciprocal of the highest dilution at \>= 50% of the replicate wells were protected from infection (MN50). The GMFR was calculated as the ratio of the post-second-booster-vaccination titer level to extension part baseline titer level. Where extension part baseline was defined as last measurement taken before the second booster vaccination.
Extension Part: SCR of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	Extension Part: Day 15, 29, 91, 181, and 366	The neutralization titer was expressed as the reciprocal of the highest dilution at \>= 50% of the replicate wells were protected from infection (MN50). SCR was defined as percentage of participants with 4-fold or more rises in titer from extension part baseline.
Extension Part: Percentage of Participants With Reported Solicited Local AEs for 7 Days Following the Second Single Booster Vaccination in Extension Part	Extension Part: 7 days after the second single booster vaccination	AE was defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product (IMP); it did not necessarily have to have a causal relationship with IMP administration. Reported solicited local AEs were defined as injection site pain, tenderness, erythema/redness, induration, and swelling.
Extension Part: Percentage of Participants With Solicited Systemic AEs for 7 Days Following the Second Single Booster Vaccination in Extension Part	Extension Part: 7 days after the second single booster vaccination	Solicited systemic AEs included were defined as fever, fatigue, malaise, myalgia, arthralgia, nausea/vomiting and headache.
Main Part: GMT of Serum Immunoglobulin G (IgG) Antibody Levels to SARS-CoV-2 Recombinant Spike (rS) Protein on Day 8, 15, 29, 91, 181, and 366	Main Part: Day 8, 15, 29, 91, 181, and 366	GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average. Titer values was measured as below LLOQ were imputed to a value that was half of the LLOQ. LLOQ was equal to 200 EU/mL.
Extension Part: Percentage of Participants With Solicited and Unsolicited SAEs Until Extension Part Day 29	Extension Part: Up to Day 29	An SAE was defined as any untoward medical occurrence that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, or is an important medical event. Solicited SAEs and unsolicited SAEs were reported.
Extension Part: Percentage of Participants With AESIs Until Extension Part Day 29	Extension Part: Up to Day 29	An AESI was defined as AEs that will be specifically highlighted to the investigator. AESIs for the study included the PIMMC and AEs specific to COVID-19. PIMMC is categorized as following; neuroinflammatory disorders, musculoskeletal and connective tissue disorders, vasculitides, gastrointestinal disorders, hepatic disorders, renal disorders, cardiac disorders, skin disorder, hematologic disorders, metabolic disorders, and other disorders.
Extension Part: Percentage of Participants With MAAEs Until Extension Part Day 29	Extension Part: Up to Day 29	MAAEs were defined as AEs leading to an unscheduled visit to or by a healthcare professional including visits to an emergency department, but not fulfilling seriousness criteria.
Extension Part: Percentage of Participants With Any AEs Leading to Withdrawal From the Trial Until Extension Part Day 29	Extension Part: Up to Day 29	Percentage of participants with any AEs leading to withdrawal from the trial until extension part Day 29 was reported.
Extension Part: Percentage of Participants With SARS-CoV-2 Infection Until Extension Part Day 29	Extension Part: Up to Day 29	Percentage of participants with SARS-CoV-2 infection until extension part Day 29 was reported.
Extension Part: Percentage of Participants With Solicited and Unsolicited SAEs Throughout the Extension Part of the Trial	Extension Part: Up to Day 366	An SAE was defined as any untoward medical occurrence that: Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, Leads to a congenital anomaly/birth defect in the offspring of a participant, or Is an important medical event. Solicited SAEs and unsolicited SAEs were reported.
Extension Part: Percentage of Participants With AESIs Throughout the Extension Part of the Trial	Extension Part: Up to Day 366	An AESI was defined as AEs that will be specifically highlighted to the Investigator. AESIs for the study included the PIMMC and AEs specific to COVID-19. PIMMC is categorized as following; neuroinflammatory disorders, musculoskeletal and connective tissue disorders, vasculitides, gastrointestinal disorders, hepatic disorders, renal disorders, cardiac disorders, skin disorder, hematologic disorders, metabolic disorders, and other disorders.
Extension Part: Percentage of Participants With MAAEs Throughout the Extension Part of the Trial	Extension Part: Up to Day 366	MAAEs were defined as AEs leading to an unscheduled visit to or by a healthcare professional including visits to an emergency department, but not fulfilling seriousness criteria.
Extension Part: Percentage of Participants With Any AEs Leading to Withdrawal From the Trial From the Day of the Second Single Booster Vaccination Throughout the Extension Part of the Trial	Extension Part: From Day 1 up to Day 366	Percentage of participants with any AEs leading to withdrawal from the trial from the day of the second single booster vaccination throughout the extension part of the trial was reported.
Extension Part: Percentage of Participants With SARS-CoV-2 Infection Throughout the Extension Part of Trial	Extension Part: Up to Day 366	Percentage of participants with SARS-CoV-2 infection throughout the extension part of trial was reported.
Extension Part: Percentage of Participants With Unsolicited AEs for 28 Days Following the Second Single Booster Vaccination in Extension Part	Extension Part: 28 days after the second single booster vaccination	Unsolicited AEs defined as AEs other than solicited local AEs and solicited systemic AEs.
Main Part: Geometric Mean Fold Rise (GMFR) of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 8, 15, 29, 91, 181, and 366	Main Part: Day 8, 15, 29, 91, 181, and 366	GMFR was calculated as the ratio of the post-vaccination titer level to the baseline titer level. Where baseline was defined as the last measurement taken before the first dose of trial vaccination.
Main Part: Seroconversion Rate (SCR) of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 8, 15, 29, 91, 181, and 366	Main Part: Day 8, 15, 29, 91, 181, and 366	SCR was defined as percentage of participants with 4-fold or more rises from baseline in titer. Baseline was defined as the last measurement taken before the first dose of trial vaccination.
Main Part: GMT of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Day 8, 15, 29, 91, 181, and 366	Main Part: Day 8, 15, 29, 91, 181, and 366	The neutralization titer was expressed as the reciprocal of the highest dilution at which greater than or equal to (\>=) 50 percent (%) of the replicate wells were protected from infection (microneutralization \[MN\] with an inhibitory concentration of 50% \[MN50\]). GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average. Titer values was measured as below LLOQ were imputed to a value that was half of the LLOQ where LLOQ was equal to 20.
Main Part: GMFR of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Day 8, 15, 29, 91, 181, and 366	Main Part: Day 8, 15, 29, 91, 181, and 366	The neutralization titer was expressed as the reciprocal of the highest dilution at which \>=50% of the replicate wells were protected from infection (MN50). GMFR was calculated as the ratio of the post-vaccination titer level to the baseline titer level. Baseline was defined as the last measurement taken before the first dose of trial vaccination.
Main Part: SCR of Serum Neutralizing Antibody Titters to the Ancestral Strain (Wild-type Virus) on Day 8, 15, 29, 91, 181, and 366	Main Part: Day 8, 15, 29, 91, 181, and 366	The neutralization titer was expressed as the reciprocal of the highest dilution at which greater than or equal to (\>=) 50% of the replicate wells were protected from infection (MN50). SCR was defined as percentage of participants with 4-fold or more rises in from baseline. Baseline was defined as the last measurement taken before the first dose of trial vaccination.
Main Part: Percentage of Participants With Solicited and Unsolicited SAEs Throughout the Main Part of Trial	Main Part: Up to Day 366	An SAE was defined as any untoward medical occurrence that: Results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, or is an important medical event. Solicited SAEs and unsolicited SAEs were reported.
Main Part: Percentage of Participants With AESI Throughout the Main Part of Trial	Main Part: Up to Day 366	An AESI was defined as AEs that will be specifically highlighted to the Investigator. AESIs for the study included the PIMMC and AEs specific to COVID-19. PIMMC is categorized as following; neuroinflammatory disorders, musculoskeletal and connective tissue disorders, vasculitides, gastrointestinal disorders, hepatic disorders, renal disorders, cardiac disorders, skin disorder, hematologic disorders, metabolic disorders, and other disorders.
Main Part: Percentage of Participants With MAAEs Throughout the Main Part of Trial	Main Part: Up to Day 366	MAAEs were defined as AEs leading to an unscheduled visit to or by a healthcare professional including visits to an emergency department, but not fulfilling seriousness criteria.

Countries

Japan

Participant flow

Recruitment details

Participants took part in the study at 2 investigative sites in Japan. Healthy Japanese participants who completed 2 doses of primary vaccinations 6 to 12 months prior to trial vaccination were enrolled to receive a first dose of single booster vaccination of TAK-019 in Main Part and a second dose of booster vaccination of TAK-019 in Extension Part.

Pre-assignment details

Participants were followed for up to 12 months after each vaccination in both parts. However, participants who remained for at least 5 months in Main Part were offered second single booster vaccination of TAK-019 in Extension Part, leading to a total participation duration of approximately 17 months.

Participants by arm

Arm	Count
Main Part: TAK-019 Participants received a first single booster vaccination of TAK-019 0.5 mL, intramuscular injection in the mid deltoid, preferable in the non-dominant upper arm at Day 1 of Main Part.	150
Total	150

Withdrawals & dropouts

Period	Reason	FG000	FG001
Extension Part: Day 1 to Day 366	Lost to Follow-up	0	2
Extension Part: Day 1 to Day 366	Other	0	1
Extension Part: Day 1 to Day 366	Withdrawal by Subject	0	5
Main Part: Day 1 up to Day 366	Lost to Follow-up	1	0
Main Part: Day 1 up to Day 366	Other	2	0
Main Part: Day 1 up to Day 366	Participants moved to extension part	129	0
Main Part: Day 1 up to Day 366	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Main Part: TAK-019
Age, Continuous	45.7 Years STANDARD_DEVIATION 13
BMI	22.68 Kilogram (kg)/meter (m)^2 STANDARD_DEVIATION 2.94
Height	164.47 Centimeter (cm) STANDARD_DEVIATION 9.408
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	150 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Region of Enrollment Japan	150 Participants
Sex: Female, Male Female	78 Participants
Sex: Female, Male Male	72 Participants
Weight	61.70 Kilograms (kg) STANDARD_DEVIATION 11.497

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 150	0 / 129
other Total, other adverse events	123 / 150	107 / 129
serious Total, serious adverse events	0 / 150	4 / 129

Outcome results

Primary

Main Part: Geometric Mean Titers (GMT) Ratio of Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Day 15 Compared With That Observed on Day 36 in Participants From the TAK-019-1501 Study

GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average for each group. Titer values was measured as below lower limit of quantification (LLOQ) were imputed to a value that was half of the LLOQ. LLOQ was equal to 20. GMT for each group and GMT ratio of neutralizing antibody titers to the ancestral strain (wild-type virus) on Day15 after a single booster vaccination (14 days after the booster vaccination) compared with that observed on Day 36 (14 days after the second vaccination) in participants from the TAK-019-1501 study (NCT04712110) were reported. GMT ratio was calculated with GMT of TAK-019-3001 on Day 15 divided by GMT of TAK-019-1501 study on Day 36. Here, ELISA is Enzyme-linked immunosorbent assay.

Time frame: Day 15 for this study (14 days after the vaccination); Day 36 for TAK-019-1501 study (14 days after the second vaccination)

Population: Per-protocol Set: PPS was defined to include participants in the Full Analysis Set (FAS) and who had evaluable immunogenicity data and did not have significant protocol deviations which influenced the immunogenicity assessment. FAS was defined as all enrolled participants who received at least 1 dose of the trial vaccination.

Arm	Measure	Value (GEOMETRIC_MEAN)
Main Part: Day 15 of This Study: TAK-019	Main Part: Geometric Mean Titers (GMT) Ratio of Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Day 15 Compared With That Observed on Day 36 in Participants From the TAK-019-1501 Study	1143.9 ELISA units per mL (EU/mL)
Day 36 for TAK-019-1501 Study	Main Part: Geometric Mean Titers (GMT) Ratio of Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Day 15 Compared With That Observed on Day 36 in Participants From the TAK-019-1501 Study	884.4 ELISA units per mL (EU/mL)

Comparison: GMT ratio was calculated GMT of TAK-019-3001 on Day 15 divided by GMT of TAK-019-1501 study on Day 36.95% CI: [0.95, 1.47]

Primary

Main Part: Percentage of Participants With Adverse Event of Special Interest (AESI) Until Day 29

An AESI was defined as AEs that will be specifically highlighted to the Investigator. AESIs for the study included the Potential Immune Mediated Medical Conditions (PIMMC) and AEs specific to COVID-19. PIMMC is categorized as following; neuroinflammatory disorders, musculoskeletal and connective tissue disorders, vasculitides, gastrointestinal disorders, hepatic disorders, renal disorders, cardiac disorders, skin disorder, hematologic disorders, metabolic disorders, and other disorders.

Time frame: Main Part: Up to Day 29

Population: Main Part: The safety analysis set included all participants who received at least 1 dose of trial vaccination.

Arm	Measure	Value (NUMBER)
Main Part: Day 15 of This Study: TAK-019	Main Part: Percentage of Participants With Adverse Event of Special Interest (AESI) Until Day 29	0 Percentage of Participants

Primary

Main Part: Percentage of Participants With Any AE Leading to Withdrawal From the Trial Until Day 29

Percentage of participants with any AE leading to withdrawal from the trial until Day 29 was reported.

Time frame: Main Part: Up to Day 29

Population: Main Part: The safety analysis set included all participants who received at least 1 dose of trial vaccination.

Arm	Measure	Value (NUMBER)
Main Part: Day 15 of This Study: TAK-019	Main Part: Percentage of Participants With Any AE Leading to Withdrawal From the Trial Until Day 29	0 Percentage of Participants

Primary

Main Part: Percentage of Participants With Medically-Attended Adverse Events (MAAEs) Until Day 29

MAAEs were defined as AEs leading to an unscheduled visit to or by a healthcare professional including visits to an emergency department, but not fulfilling seriousness criteria.

Time frame: Main Part: Up to Day 29

Population: Main Part: The safety analysis set included all participants who received at least 1 dose of trial vaccination.

Arm	Measure	Value (NUMBER)
Main Part: Day 15 of This Study: TAK-019	Main Part: Percentage of Participants With Medically-Attended Adverse Events (MAAEs) Until Day 29	0.7 Percentage of Participants

Primary

Main Part: Percentage of Participants With Reported Solicited Local Adverse Events (AEs) for 7 Days Following the First Single Booster Vaccination

AE was defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product (IMP); it did not necessarily have to have a causal relationship with IMP administration. Reported solicited local AEs were defined as injection site pain, tenderness, erythema/redness, induration, and swelling.

Time frame: Main Part: 7 days after the first single booster vaccination

Population: Main Part: The safety analysis set included all participants who received at least 1 dose of the trial vaccination.

Arm	Measure	Value (NUMBER)
Main Part: Day 15 of This Study: TAK-019	Main Part: Percentage of Participants With Reported Solicited Local Adverse Events (AEs) for 7 Days Following the First Single Booster Vaccination	74.0 Percentage of Participants

Primary

Main Part: Percentage of Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection Until Day 29

Percentage of participants with SARS-CoV-2 infection until Day 29 of the main part of the trial were reported in this outcome measure.

Time frame: Main Part: Up to Day 29

Population: Main Part: The safety analysis set included all participants who received at least 1 dose of trial vaccination.

Arm	Measure	Value (NUMBER)
Main Part: Day 15 of This Study: TAK-019	Main Part: Percentage of Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection Until Day 29	0 Percentage of Participants

Primary

Main Part: Percentage of Participants With Solicited and Unsolicited Serious Adverse Events (SAE) Until Day 29

An SAE was defined as any untoward medical occurrence that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, or is an important medical event. Solicited SAEs and unsolicited SAEs were reported.

Time frame: Main Part: Up to Day 29

Population: Main Part: The safety analysis set included all participants who received at least 1 dose of trial vaccination.

Arm	Measure	Group	Value (NUMBER)
Main Part: Day 15 of This Study: TAK-019	Main Part: Percentage of Participants With Solicited and Unsolicited Serious Adverse Events (SAE) Until Day 29	Solicited SAEs up to Day 29	0 Percentage of Participants
Main Part: Day 15 of This Study: TAK-019	Main Part: Percentage of Participants With Solicited and Unsolicited Serious Adverse Events (SAE) Until Day 29	Unsolicited SAEs up to Day 29	0 Percentage of Participants

Primary

Main Part: Percentage of Participants With Solicited Systemic AEs for 7 Days Following the First Single Booster Vaccination

Solicited systemic AEs were defined as fever, fatigue, malaise, myalgia, arthralgia, nausea/vomiting, and headache.

Time frame: Main Part: 7 days after the first single booster vaccination

Population: Main Part: The safety analysis set included all participants who received at least 1 dose of the trial vaccination.

Arm	Measure	Value (NUMBER)
Main Part: Day 15 of This Study: TAK-019	Main Part: Percentage of Participants With Solicited Systemic AEs for 7 Days Following the First Single Booster Vaccination	48.0 Percentage of Participants

Primary

Main Part: Percentage of Participants With Unsolicited AEs for 28 Days Following the First Single Booster Vaccination

Unsolicited AEs defines as other AEs than solicited local AEs and solicited systemic AEs.

Time frame: Main Part: 28 days after the first single booster vaccination

Population: Main Part: The safety analysis set included all participants who received at least 1 dose of trial vaccination.

Arm	Measure	Value (NUMBER)
Main Part: Day 15 of This Study: TAK-019	Main Part: Percentage of Participants With Unsolicited AEs for 28 Days Following the First Single Booster Vaccination	4.67 Percentage of Participants

Secondary

Extension Part: GMFR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Extension Part Day 15, 29, 91, 181, and 366

The GMFR was calculated as the ratio of the post-second-booster-vaccination titer level to extension part baseline titer level. Where extension part baseline was defined as last measurement taken before the second booster vaccination.

Time frame: Extension Part: Day 15, 29, 91, 181, and 366

Population: Extension part PPS was defined to include participants in the FAS in the Extension Part who had evaluable immunogenicity data and did not have significant protocol deviations which influenced the immunogenicity assessment. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specified timepoints.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMFR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Extension Part Day 15, 29, 91, 181, and 366	At Day 15	3.99 fold rise
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMFR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Extension Part Day 15, 29, 91, 181, and 366	At Day 29	3.32 fold rise
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMFR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Extension Part Day 15, 29, 91, 181, and 366	At Day 91	2.30 fold rise
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMFR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Extension Part Day 15, 29, 91, 181, and 366	At Day 181	1.72 fold rise
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMFR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Extension Part Day 15, 29, 91, 181, and 366	At Day 366	2.33 fold rise

Secondary

Extension Part: GMFR of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366

The neutralization titer was expressed as the reciprocal of the highest dilution at \>= 50% of the replicate wells were protected from infection (MN50). The GMFR was calculated as the ratio of the post-second-booster-vaccination titer level to extension part baseline titer level. Where extension part baseline was defined as last measurement taken before the second booster vaccination.

Time frame: Extension Part: Day 15, 29, 91, 181, and 366

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMFR of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	At Day 15	3.04 fold rise
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMFR of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	At Day 29	3.05 fold rise
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMFR of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	At Day 91	2.19 fold rise
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMFR of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	At Day 181	2.34 fold rise
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMFR of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	At Day 366	1.16 fold rise

Secondary

Extension Part: GMT of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 15, 29, 91, 181, and 366

GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average. Titer values was measured as below LLOQ were imputed to a value that was half of the LLOQ. LLOQ was equal to 200 EU/mL.

Time frame: Extension Part: Day 15, 29, 91, 181, and 366

Population: Extension Part PPS was defined to include participants in the FAS in the Extension Part who had evaluable immunogenicity data and did not have significant protocol deviations which influenced the immunogenicity assessment. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specified timepoints.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMT of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 15, 29, 91, 181, and 366	At Day 15	105057.6 EU/mL
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMT of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 15, 29, 91, 181, and 366	At Day 29	88154.1 EU/mL
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMT of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 15, 29, 91, 181, and 366	At Day 91	61090.0 EU/mL
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMT of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 15, 29, 91, 181, and 366	At Day 181	46199.1 EU/mL
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMT of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 15, 29, 91, 181, and 366	At Day 366	62823.7 EU/mL

Secondary

Extension Part: GMT of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366

The neutralization titer was expressed as the reciprocal of the highest dilution at \>= 50% of the replicate wells were protected from infection (MN50). GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average. Titer values was measured as below LLOQ were imputed to a value that was half of the LLOQ where LLOQ was equal to 20.

Time frame: Extension Part: Day 15, 29, 91, 181, and 366

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMT of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	At Day 15	1716.6 1 per dilution
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMT of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	At Day 29	1732.1 1 per dilution
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMT of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	At Day 91	1255.4 1 per dilution
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMT of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	At Day 181	1360.7 1 per dilution
Main Part: Day 15 of This Study: TAK-019	Extension Part: GMT of Serum Neutralizing Antibody Titers to the Ancestral Strain (Wild-type Virus) on Extension Part Day 15, 29, 91, 181, and 366	At Day 366	660.0 1 per dilution

Secondary

Extension Part: Percentage of Participants With AESIs Throughout the Extension Part of the Trial

An AESI was defined as AEs that will be specifically highlighted to the Investigator. AESIs for the study included the PIMMC and AEs specific to COVID-19. PIMMC is categorized as following; neuroinflammatory disorders, musculoskeletal and connective tissue disorders, vasculitides, gastrointestinal disorders, hepatic disorders, renal disorders, cardiac disorders, skin disorder, hematologic disorders, metabolic disorders, and other disorders.

Time frame: Extension Part: Up to Day 366