A Study of TAK-019 in Healthy Japanese Adults (COVID-19)

Study Overview
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Brief Summary
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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. At the first visit, the study doctor will check if each person can take part. Those who can take part will be chosen for 1 of 2 treatments by chance. Participants will either receive an injection of TAK-019 or a placebo in their arm. In this study, a placebo will look like the TAK-019 vaccine but will not have any medicine in it. 3 times as many participants will receive TAK-019 than placebo. Participants will receive 2 injections of TAK-019 or placebo, 21 days apart. Participants will be asked to record their temperature and any medical problems in an electronic diary for up to 7 days after each injection. During the study, 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 their 2nd injection, the study sponsor (Takeda) will check how many participants have made enough antibodies to protect them against Covid-19. The participants will stay in the study for up to 12 months after they have had their 2nd injection. During this time, the study doctors will continue to check how many participants have made enough antibodies to protect them against Covid-19. Also, they will check if participants have any more side effects from TAK-019 or the placebo.

Detailed Description
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The drug being tested in this study is called TAK-019. TAK-019 is being tested to prevent infectious disease caused by Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2). This study will look at the evaluate the safety and immunogenicity of 2 doses of TAK-019 by intramuscular (IM) injection 21 days apart in healthy Japanese male and female adults. The study will enroll approximately 200 healthy volunteers. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): TAK-019 0.5 mL Placebo- this is an injection that looks like the study drug but has no active ingredient All participants will be asked to take intramuscular injection in the upper arm twice throughout the study. This multi-center trial will be conducted in Japan. The overall time to participate in this study is 12 months from the second vaccination (totally 387 days). Participants will make multiple visits to the clinic and will be contacted by telephone or a final visit after the last vaccination for a follow-up assessment.

Official Title
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A Phase 1/2, Randomized, Observer-Blind, Placebo-Controlled Trial to Evaluate the Safety and Immunogenicity of TAK-019 by Intramuscular Injection in Healthy Japanese Male and Female Adults Aged 20 Years and Older (COVID-19)

Conditions
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Prevention of Infection Disease Caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)

Intervention / Treatment
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* Biological: TAK-019
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Japanese male and female adult participants aged >= 20 years of age at the time of signing of informed consent. Participants who understand and are willing to comply with trial procedures and are available for the duration of follow-up. Exclusion Criteria: Participants who received any other SARS-CoV-2 or other experimental novel coronavirus vaccine prior to the trial. Participants who have close contact of anyone known to have COVID-19 within 30 days prior to the trial vaccination. Participants who were tested positive for SARS-CoV-2 prior to the trial or before the trial vaccination. Participants who are on current treatment with other investigational agents for prophylaxis of COVID-19. Participants who have traveled outside of Japan in the 30 days prior to the trial participation. Participants with a clinically significant active infection (as assessed by the Investigator) or oral temperature >= 38 degree Celsius within 3 days of the intended date of vaccination. Participants with known hypersensitivity or allergy to any of the investigational vaccine components. Participants with history or any illness that, in the opinion of the Investigator, might interfere with the results of the trial or pose additional risk to the participants due to participation in the trial. Participants with known or suspected impairment/alteration of immune function, including history of any autoimmune disease or neuro-inflammatory disease. Abnormalities of splenic or thymic function. Participants with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. Participants with any serious chronic or progressive disease (eg, neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease). Participants with body mass index (BMI) greater than or equal to 30 kg/m^2 (BMI= weight in kg/ height in meters^2). Participants participating in any clinical trial with another investigational product within 30 days prior to the trial vaccination or intend to participate in another clinical trial at any time during the conduct of this trial. Participants who received or plan to receive any other licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to trial dose administration. Participants with acute or chronic clinically significant disease including pulmonary, cardiovascular, hepatic or renal abnormality evaluated by physical examination. Participants involved in the trial conduct or their first degree relatives. Participants who have history or infection of hepatitis B, hepatitis C, and human immunodeficiency virus infection. Female participants who are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-019<br>TAK-019 0.5 mL, intramuscular injection in the upper arm | Biological: TAK-019<br>* TAK-019 intramuscular injection<br>|
| Placebo Comparator: Placebo<br>TAK-019 Matching Placebo, intramuscular injection in the upper arm | Biological: Placebo<br>* Placebo intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Solicited Local Adverse Events (AEs) for Six Subsequent Days Following First Vaccination | Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their diary for six subsequent days following first vaccination. Solicited local AEs included injection site pain, tenderness, erythema/redness, induration, and swelling. | Up to Day 7 (6 subsequent days after first vaccination on Day 1) | 
| Percentage of Participants With Solicited Local AEs for Six Subsequent Days Following Second Vaccination | Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their diary for six subsequent days following second vaccination. Solicited local AEs included injection site pain, tenderness, erythema/redness, induration, and swelling. | Up to Day 28 (6 subsequent days after second vaccination on Day 22) | 
| Percentage of Participants With Solicited Systemic AEs for Six Subsequent Days Following First Vaccination | Solicited systemic AEs were pre-defined AEs for which participants were specifically questioned and which were noted by participants in their diary for six subsequent days following first vaccination. Solicited systemic AEs included fever, fatigue, malaise, myalgia, arthralgia, nausea/vomiting and headache. | Up to Day 7 (6 subsequent days after first vaccination on Day 1) | 
| Percentage of Participants With Solicited Systemic AEs for Six Subsequent Days Following Second Vaccination | Solicited systemic AEs were pre-defined AEs for which participants were specifically questioned and which were noted by participants in their diary for six subsequent days following second vaccination. Solicited systemic AEs included fever, fatigue, malaise, myalgia, arthralgia, nausea/vomiting and headache. | Up to Day 28 (6 subsequent days after second vaccination on Day 22) | 
| Percentage of Participants With Unsolicited AEs for 20 Days Following First Vaccination | Unsolicited AEs were all AEs that were not pre-defined for which the participant was not specifically questioned in the participant diary. | Up to Day 21 (20 days after first vaccination on Day 1) | 
| Percentage of Participants With Unsolicited AEs for 27 Days Following Second Vaccination | Unsolicited AEs were all AEs that were not pre-defined for which the participant was not specifically questioned in the participant diary. | Up to Day 49 (27 days after second vaccination on Day 22) | 
| Percentage of Participants With Serious Adverse Events (SAEs) Until Day 50 | Only unsolicited SAEs data was planned to be collected and assessed for the assessment of this outcome measure (OM) and solicited SAE was out of the scope of assessment. Unsolicited SAEs were those AEs that were not pre-defined for which the participant was not specifically questioned in the participant diary. Percentage of participants with unsolicited SAEs until Day 50 were reported in this outcome measure. | Day 1 up to Day 50 | 
| Percentage of Participants With Adverse Events of Special Interest (AESI) Until Day 50 | AESIs were defined as AEs that were specifically highlighted to the Investigator. Only unsolicited AESI data was planned to be collected and assessed for the assessment of this OM and solicited AESI was out of the scope of assessment. Unsolicited AESIs were those AEs that were not pre-defined for which the participant was not specifically questioned in the participant diary. Percentage of participants with unsolicited AESIs until Day 50 were reported in this outcome measure. | Day 1 up to Day 50 | 
| Percentage of Participants With Medically-Attended Adverse Events (MAAEs) Until Day 50 | MAAEs are 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. Only unsolicited MAAEs data was planned to be collected and assessed for the assessment of this OM and solicited MAAE was out of the scope of assessment. Unsolicited MAAEs were those AEs that were not pre-defined for which the participant was not specifically questioned in the participant diary. Percentage of participants with unsolicited MAAEs until Day 50 were reported in this outcome measure. | Day 1 up to Day 50 | 
| Percentage of Participants With Any AE Leading to Discontinuation of Vaccination | Only any unsolicited AE leading to discontinuation of vaccination data was planned to be collected and assessed for the assessment of this OM and solicited AE leading to discontinuation of vaccination was out of the scope of assessment. Unsolicited AEs were those AEs that were not pre-defined for which the participant was not specifically questioned in the participant diary. Percentage of participants with any unsolicited AE leading to discontinuation of vaccination until Day 22 were reported in this outcome measure. | Day 1 up to Day 22 | 
| Percentage of Participants With Any AE Leading to Participant's Withdrawal From the Trial Until Day 50 | Only any unsolicited AE leading to participant's withdrawal from the trial data was planned to be collected and assessed for the assessment of this OM and solicited AE leading to participant's withdrawal from the trial was out of the scope of assessment. Unsolicited AEs were those AEs that were not pre-defined for which the participant was not specifically questioned in the participant diary. Percentage of participants with any unsolicited AE leading to participant's withdrawal from the trial until Day 50 were reported in this outcome measure. | Day 1 up to Day 50 | 
| Percentage of Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection Until Day 50 |  | Day 1 up to Day 50 | 
| Geometric Mean Titers (GMT) of Serum Immunoglobulin G (IgG) Antibody Levels to SARS-CoV-2 Recombinant Spike (rS) Protein on Day 36 | 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 200. Here, ELISA is Enzyme-linked immunosorbent assay. | At Day 36 | 
| Geometric Mean Fold Rise (GMFR) of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 36 | 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 study intervention. | At Day 36 | 
| Seroconversion Rate (SCR) of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 36 | SCR was defined as percentage of participants with 4-fold or more rises in titer if naive at baseline OR percentage of participants with 2-fold or more rises in titer if seropositive at baseline. Baseline was defined as the last measurement taken before the first dose of study intervention. | At Day 36 | 
| Seroresponse Rate (SRR) of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 36 | SRR was defined as percentage of participants with greater than or equal to (>=) 95 percentile in titer at Baseline for all participants. Baseline was defined as the last measurement taken before the first dose of study intervention. | At Day 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With SAE Throughout the Trial | Only unsolicited SAEs data was planned to be collected and assessed for the assessment of this OM and solicited SAE was out of the scope of assessment. Unsolicited SAEs were those AEs that were not pre-defined for which the participant was not specifically questioned in the participant diary. Percentage of participants with unsolicited SAEs throughout the trial were reported in this outcome measure. | Day 1 up to Day 387 | 
| Percentage of Participants With AESI Throughout the Trial | AESIs were defined as AEs that were specifically highlighted to the Investigator. Only unsolicited AESI data was planned to be collected and assessed for the assessment of this OM and solicited AESI was out of the scope of assessment. Unsolicited AESI were those AEs that were not pre-defined for which the participant was not specifically questioned in the participant diary. Percentage of participants with unsolicited AESIs throughout the trial were reported in this outcome measure. | Day 1 up to Day 387 | 
| Percentage of Participants With MAAEs Throughout the Trial | MAAEs are 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. Only unsolicited MAAEs data was planned to be collected and assessed for the assessment of this OM and solicited MAAE was out of the scope of assessment. Unsolicited MAAEs were those AEs that were not pre-defined for which the participant was not specifically questioned in the participant diary. Percentage of participants with unsolicited MAAEs throughout the trial were reported in this outcome measure. | Day 1 up to Day 387 | 
| Percentage of Participants With Any AE Leading to Participant's Withdrawal From the Trial From the Day of Vaccination Throughout the Trial | Only any unsolicited AE leading to participant's withdrawal from the trial data was planned to be collected and assessed for the assessment of this OM and solicited AE leading to participant's withdrawal from the trial was out of the scope of assessment. Unsolicited AEs were those AEs that were not pre-defined for which the participant was not specifically questioned in the participant diary. Percentage of participants with any unsolicited AE leading to withdrawal from the trial from the day of vaccination throughout the trial were reported in this outcome measure. | Day 1 up to Day 387 | 
| Percentage of Participants With SARS-CoV-2 Infection Throughout the Trial |  | Day 1 up to Day 387 | 
| GMT of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Days 22, 50, 202, and 387 | GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average for each group. Titer values was measured as below LLOQ were imputed to a value that was half of the LLOQ. GMT of serum IgG antibody levels to the SARS-CoV-2 rS protein was measured where LLOQ was equal to 200. | At Days 22, 50, 202, and 387 | 
| GMFR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Days 22, 50, 202, and 387 | 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 study intervention. | At Days 22, 50, 202, and 387 | 
| SCR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Days 22, 50, 202, and 387 | SCR was defined as percentage of participants with 4-fold or more rises in titer if naive at baseline OR percentage of participants with 2-fold or more rises in titer if seropositive at baseline. Baseline was defined as the last measurement taken before the first dose of study intervention. | At Days 22, 50, 202, and 387 | 
| SRR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Days 22, 50, 202, and 387 | SRR was defined as percentage of participants with >=95 percentile in titer at Baseline for all participants. Baseline was defined as the last measurement taken before the first dose of study intervention. | At Days 22, 50, 202, and 387 | 
| GMT of Serum Neutralizing Antibody (nAb) Titers to Wild Type Virus on Days 22, 36, 50, 202 and Day 387 | 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). GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average for each group. Titer values was measured as below LLOQ were imputed to a value that was half of the LLOQ. GMT of serum IgG antibody levels to the SARS-CoV-2 rS protein was measured where LLOQ was equal to 20. | At Days 22, 36, 50, 202 and 387 | 
| GMFR of Serum nAb Titers to Wild Type Virus on Days 22, 36, 50, 202 and 387 | 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 study intervention. | At Days 22, 36, 50, 202 and 387 | 
| SCR to Serum nAb Titers to Wild Type Virus on Days 22, 36, 50, 202 and 387 | The neutralization titer was expressed as the reciprocal of the highest dilution at which >=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 if naive at baseline OR percentage of participants with 2-fold or more rises in titer if seropositive at Baseline. Baseline was defined as the last measurement taken before the first dose of study intervention. | At Days 22, 36, 50, 202 and 387 | 
| SRR to Serum nAb Titers to Wild Type Virus on Days 22, 36, 50, 202 and 387 | The neutralization titer was expressed as the reciprocal of the highest dilution at which >=50% of the replicate wells were protected from infection (MN50). SRR was defined as percentage of participants with >=95 percentile in titer at Baseline for all participants. Baseline was defined as the last measurement taken before the first dose of study intervention. | At Days 22, 36, 50, 202 and 387 |