A Study of TAK-919 in Healthy Japanese Adults (COVID-19)

Study Overview
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Brief Summary
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TAK-919 is a vaccine in development to protect people against Covid-19. The main aims of the study are to learn if TAK-919 can protect people from Covid-19 and to check for side effects from TAK-919. 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-919 or a placebo in their arm. In this study, a placebo will look like the TAK-919 vaccine but will not have any medicine in it. 3 times as many participants will receive TAK-919 than placebo. Participants will receive 2 injections of TAK-919 or placebo, 28 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 visited their clinic 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-919 or the placebo.

Detailed Description
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The drug being tested in this study is called TAK-919. TAK-919 is being tested to prevent infectious disease caused by Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2). This study will look at the safety and immunogenicity of 2 doses of TAK-919 by intramuscular (IM) injection in healthy Japanese male and female adults, given 28 days apart. 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-919 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. 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-919 by Intramuscular Injection in Healthy Japanese Male and Female Adults Aged 20 Years and Older (COVID-19)

Conditions
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Coronavirus Disease (COVID-19)

Intervention / Treatment
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* Biological: TAK-919
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Japanese male and female participants. 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 vaccine administration. Participants who were tested positive for SARS-CoV-2 prior to the trial or on the test before the vaccination. Participants who are on current treatment with other investigational agents for prophylaxis of COVID 19. Participants who 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 vaccination. Participants with a known hypersensitivity or allergy to any of the IMP components. Participants with any illness or history of 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 BMI >= 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 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 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 are with or have history of hepatitis B and hepatitis C infection, or with known human immunodeficiency virus (HIV) infection or HIV-related disease.. 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-919<br>TAK-919 0.5 mL, intramuscular injection in the upper arm | Biological: TAK-919<br>* TAK-919 intramuscular injection<br>|
| Placebo Comparator: Placebo<br>TAK-919 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, erythema/redness, swelling, induration, and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. | 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, erythema/redness, swelling, induration, and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. | Up to Day 35 (6 subsequent days after second vaccination on Day 29) | 
| 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 headache, fatigue, myalgia, arthralgia, nausea/ vomiting, chills, fever. | 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 headache, fatigue, myalgia, arthralgia, nausea/ vomiting, chills, fever. | Up to Day 35 (6 subsequent days after second vaccination on Day 29) | 
| Percentage of Participants With Unsolicited AEs for 28 Days Following First Vaccination | Unsolicited AEs were all AEs that were not pre-defined for which the participant is not specifically questioned in the participant diary. | Up to Day 29 (28 days after first vaccination on Day 1) | 
| Percentage of Participants With Unsolicited AEs for 28 Days Following Second Vaccination | Unsolicited AEs were all AEs that were not pre-defined for which the participant is not specifically questioned in the participant diary. | Up to Day 57 (28 days after second vaccination on Day 29) | 
| Percentage of Participants With Serious Adverse Events (SAEs) Until Day 57 | 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 the assessment. Unsolicited SAEs were those AEs that were not pre-defined for which the participant is not specifically questioned in the participant diary. Percentage of participants with unsolicited SAEs until Day 57 was reported in this outcome measure. | Day 1 up to Day 57 | 
| Percentage of Participants With Medically-Attended Adverse Events (MAAEs) Until Day 57 | 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. Only unsolicited MAAEs data was planned to be collected and assessed for the assessment of this OM and solicited MAAEs was out of the scope of the assessment. Unsolicited MAAEs were those AEs that were not pre-defined for which the participant is not specifically questioned in the participant diary. Percentage of participants with unsolicited MAAEs until Day 57 was reported in this outcome measure. | Day 1 up to Day 57 | 
| Percentage of Participants With Any AE Leading to Discontinuation of Vaccination | Only 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 the assessment. Unsolicited AEs were those AEs that were not pre-defined for which the participant is not specifically questioned in the participant diary. Percentage of participants with any unsolicited AE leading to discontinuation of vaccination was reported in this outcome measure. | Day 1 up to Day 57 | 
| Percentage of Participants With Any AE Leading to Participant's Withdrawal From the Trial Until Day 57 | Only unsolicited AE leading to participant's withdrawal data was planned to be collected and assessed for the assessment of this OM and solicited AE leading to participant's withdrawal was out of the scope of the assessment. Unsolicited AEs were those AEs that were not pre-defined for which the participant is not specifically questioned in the participant diary. Percentage of participants with any unsolicited AE leading to participant's withdrawal from the trial until Day 57 was reported in this outcome measure. | Day 1 up to Day 57 | 
| Percentage of Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection Until Day 57 |  | Day 1 up to Day 57 | 
| Geometric Mean Titers (GMT) of Serum Binding Antibody (bAb) Against SARS-CoV-2 on Day 57 | GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average for each group. Titer values measured as below lower limit of quantification (LLOQ) were imputed to a value that is half of the LLOQ. Titer values measured as above upper limit of quantification (ULOQ) were imputed at the ULOQ value. LLOQ=1 and ULOQ= 2052. GMT of serum bAb against SARS-CoV-2 was measured by ligand-binding assay specific to the SARS-CoV-2 spike (S) protein. | At Day 57 | 
| Geometric Mean Fold Rise (GMFR) of Serum bAb Against SARS-CoV-2 on Day 57 | The 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. GMFR of serum bAb against SARS-CoV-2 was measured by ligand-binding assay specific to the SARS-CoV-2 S protein. | At Day 57 | 
| Seroconversion Rate (SCR) of Serum bAb Against SARS-CoV-2 on Day 57 | SCR was defined as percentage of participants with a change from below limit of detection (LOD) or LLOQ to equal to or above LOD or LLOQ, OR, greater than or equal to (>=) 4-fold rises from baseline. LLOQ= 1, ULOQ= 2052. Baseline was defined as the last measurement taken before the first dose of study intervention. SCR of serum bAb against SARS-CoV-2 was measured by ligand-binding assay specific to the SARS-CoV-2 S protein. | At Day 57 | 

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 the assessment. Unsolicited SAEs were those AEs that were not pre-defined for which the participant is not specifically questioned in the participant diary. Percentage of participants with unsolicited SAEs throughout the trial was reported in this outcome measure. | Day 1 up to Day 394 | 
| Percentage of Participants With MAAEs Throughout the Trial | 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. Only unsolicited MAAEs data was planned to be collected and assessed for the assessment of this OM and solicited MAAEs was out of the scope of the assessment. Unsolicited MAAEs were those AEs that were not pre-defined for which the participant is not specifically questioned in the participant diary. Percentage of participants with unsolicited MAAEs throughout the trial was reported in this outcome measure. | Day 1 up to Day 394 | 
| Percentage of Participants With Any AE Leading to Participant's Withdrawal From the Trial From the Day of Vaccination Throughout the Trial | Only unsolicited AE leading to participant's withdrawal data was planned to be collected and assessed for the assessment of this OM and solicited AE leading to participant's withdrawal was out of the scope of the assessment. Unsolicited AEs were those AEs that were not pre-defined for which the participant is not specifically questioned in the participant diary. Percentage of participants with any unsolicited AE leading to participant's withdrawal from the trial from the day of vaccination throughout the trial was reported in this outcome measure. | Day 1 up to Day 394 | 
| Percentage of Participants With SARS-CoV-2 Infection Throughout the Trial |  | Day 1 up to Day 394 | 
| GMT of Serum bAb Against SARS-CoV-2 on Days 29, 43, 209 and 394 | GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average for each group. Titer values measured as below LLOQ were imputed to a value that is half of the LLOQ. Titer values measured as above ULOQ were imputed at the ULOQ value. LLOQ=1 and ULOQ= 2052 until Day 43; LLOQ= 1 and ULOQ= 20520 from Day 209 and later. GMT of serum bAb against SARS-CoV-2 was measured by ligand-binding assay specific to the SARS-CoV-2 S protein. | At Days 29, 43, 209 and 394 | 
| GMFR of Serum bAb Against SARS-CoV-2 on Days 29, 43, 209 and 394 | The 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. GMFR of serum bAb against SARS-CoV-2 was measured by ligand-binding assay specific to the SARS-CoV-2 S protein. | At Days 29, 43, 209 and 394 | 
| SCR of Serum bAb Against SARS-CoV-2 on Days 29, 43, 209 and 394 | SCR was defined as percentage of participants with a change from below LOD or LLOQ to equal to or above LOD or LLOQ, OR >=4-fold rises from baseline. LLOQ= 1 and ULOQ= 2052 until Day 43; LLOQ= 1 and ULOQ= 20520 from Day 209 and later. Baseline was defined as the last measurement taken before the first dose of study intervention. SCR of serum bAb against SARS-CoV-2 was measured by ligand-binding assay specific to the SARS-CoV-2 S protein. | At Days 29, 43, 209 and 394 | 
| GMT of Serum Neutralizing Antibody (nAb) Against SARS-CoV-2 on Days 29, 43, 57, 209, and 394 | GMT was the immunogenicity outcome expressed as reciprocal antibody titer with average for each group. Titer values measured as below LLOQ were imputed to a value that is half of the LLOQ. Titer values measured as above ULOQ were imputed at the ULOQ value. LLOQ= 159.79 and ULOQ= 11173.11. GMT of serum nAb against SARS-CoV-2 was measured by assay specific to wild-type virus. | At Days 29, 43, 57, 209, and 394 | 
| GMFR of Serum nAb Against SARS-CoV-2 on Days 29, 43, 57, 209, and 394 | The 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. GMFR of serum nAb against SARS-CoV-2 was measured by assay specific to wild-type virus. | At Days 29, 43, 57, 209, and 394 | 
| SCR of Serum nAb Against SARS-CoV-2 on Days 29, 43, 57, 209, and 394 | SCR was defined at percentage of participants with a change from below the LOD or LLOQ to equal to or above LLOQ, OR, >=4-fold rises from baseline. LLOQ= 159.79 and ULOQ= 11173.11. Baseline was defined as the last measurement taken before the first dose of study intervention. SCR of serum nAb against SARS-CoV-2 was measured by assay specific to wild-type virus. | At Days 29, 43, 57, 209, and 394 |