Safety Immunogenicity Study of MT-2766 in Japanese Adults（COVID-19）

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and immunogenicity of MT-2766 in Japanese adults.

Official Title
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A Phase I/II, Randomized, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of MT-2766 in Japanese Adults (COVID-19)

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Biological: MT-2766 High dose (3.75 µg)
* Drug: Placebo
* Biological: MT-2766 Low dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Subjects must meet all of the following inclusion criteria at the Screening visit (Visit 1) and/or 1st vaccination visit (Visit 2) to be eligible for participation in this study. All Investigator assessment-based judgments must be carefully and fully documented in the source documents: Subjects must have read, understood, and signed the informed consent form (ICF) prior to participating in the study; subjects must also complete study-related procedures and must communicate with the study staff at visits and by phone during the study; At the Screening visit (Visit 1), Japanese male and female subjects must be ≥20 years of age; At the Screening visit (Visit 1) and 1st vaccination visit (Visit 2), subject must have a body mass index (BMI) of ≥18.5 kg/m^2 and <30 kg/m^2; Subjects are considered by the Investigator to be reliable and likely to cooperate with the assessment procedures and be available for the duration of the study; Female subjects of childbearing potential must have a negative serum pregnancy test result at the Screening visit (Visit 1) and a negative urine pregnancy test result at 1st vaccination visit (Visit 2): Non-childbearing females are defined as: Surgically sterile (defined as bilateral tubal ligation, hysterectomy or bilateral oophorectomy performed more than one month prior to the first study vaccination); OR Post-menopausal (absence of menses for 12 consecutive months and age consistent with natural cessation of ovulation); Female subjects of childbearing potential must use an effective method of contraception for one month prior to 1st vaccination visit (Visit 2) and agree to continue employing highly effective birth control measures for at least one month after the last study vaccination (or in the case of early termination, she must not plan to become pregnant for at least one month after her last study vaccination); Subjects must be non-institutionalized (e.g. not living in rehabilitation centers or old-age homes); Subjects have no acute or evolving medical problems prior to study participation and no clinically relevant abnormalities that could jeopardize subject safety or interfere with study assessments, as assessed by the Principal Investigator or sub-Investigator (thereafter referred as Investigator) and determined by medical history, physical examination, serology, clinical chemistry and hematology tests, urinalysis, and vital signs. Investigator discretion is permitted with this inclusion criterion. Exclusion Criteria: Subjects who meet any of the following exclusion criteria at the Screening visit (Visit 1) and/or 1st vaccination visit (Visit 2) will not be eligible for participation in this study. All Investigator assessment-based judgments must be carefully and fully documented in the source documents: According to the Investigator's opinion, significant acute or chronic, uncontrolled medical or neuropsychiatric illness. Acute disease is defined as presence of any moderate or severe acute illness with or without a fever within 48 hours prior to the Screening visit (Visit 1) and/or 1st vaccination visit (Visit 2). 'Uncontrolled' is defined as: Requiring a new medical or surgical treatment during the three months prior to study vaccine administration; Requiring any significant change in a chronic medication (i.e. drug, dose, frequency) during the three months prior to study vaccine administration due to uncontrolled symptoms or drug toxicity unless the innocuous nature of the medication change meets the criteria outlined in inclusion criterion no. 8 and is appropriately justified by the Investigator. Investigator discretion is permitted with this exclusion criterion. 2. Any confirmed or suspected current immunosuppressive condition or immunodeficiency, including cancer, HIV, hepatitis B or C infection (subjects with a history of cured hepatitis B or C infection without any signs of immunodeficiency at present time are allowed). Investigator discretion is permitted with this exclusion criterion; 3. Current autoimmune disease (such as rheumatoid arthritis, systemic lupus erythematosus or multiple sclerosis). Investigator discretion is permitted with this exclusion criterion. Subjects may be eligible to participate with appropriate written justification in the source document. For example, subjects with a history of autoimmune disease who are disease-free without treatment for three years or more, subjects receiving stable thyroid replacement therapy, and subjects with mild psoriasis (i.e. a small number of minor plaques requiring no systemic treatment) are eligible for participation; 4. Administration of any medication or treatment that may alter the vaccine immune responses, such as: Systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or equivalent) per day for more than seven consecutive days or for 10 or more days in total, within one month prior to the 1st vaccination visit (Visit 2). Inhaled, nasal, ophthalmic, dermatological, and other topical glucocorticoids are permitted; Cytotoxic, antineoplastic, or immunosuppressant drugs - within 36 months prior to 1st vaccination visit (Visit 2); Any immunoglobulin preparations, blood products, or blood transfusion - within 6 months prior to 1st vaccination visit (Visit 2); 5. Administration of any vaccine within 14 days prior to 1st vaccination visit (Visit 2); planned administration of any vaccine during the study (up to Day 28). Immunization on an emergency basis during the study will be evaluated on case-by-case basis by the Investigator; 6. Administration of any other SARS-CoV-2/COVID-19 vaccine, or other experimental coronavirus vaccine at any time prior to or during the study; 7. At screening (Visit 1), subjects found to be seropositive for prior SARS-COV-2 infection based on N-protein ELISA or positive for SARS-COV-2 PCR test; 8. Subjects with previous diagnosis of COVID-19 or previous positive SARS-CoV-2 infection 9. Use of any investigational or non-registered product within 30 days or 5 half-lives, whichever is longer, prior to 1st vaccination visit (Visit 2), or planned use during the study period. Subjects who are in a prolonged post-administration observation period of another investigational or marketed drug clinical study, for which there is no ongoing exposure to the investigational or marketed product and all scheduled on-site visits are completed, will be allowed to take part in this study, if all other eligibility criteria are met; 10. Have a rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at injection site that may interfere with injection site reaction rating. Investigator discretion is permitted with this exclusion criterion: 11. Use of any prescription antiviral drugs with the intention of COVID-19 prophylaxis, including those that are thought to be effective for prevention of COVID-19 but have not been licensed for this indication, within one month prior to 1st vaccination visit (Visit 2); 12. Use of prophylactic medications (e.g. antihistamines [H1 receptor antagonists], nonsteroidal anti-inflammatory drugs [NSAIDs], systemic and topical glucocorticoids, non-opioid and opioid analgesics) within 24 hours prior to the 1st vaccination (Visit 2) to prevent or pre-empt symptoms due to vaccination; 13. History of a serious allergic response to any of the constituents of MT-2766; 14. History of a documented anaphylactic reactions to plants or plant components (including tobacco, fruits, and nuts); 15. Personal or family (first-degree relatives) history of narcolepsy; 16. Subjects with a history of Guillain-Barré Syndrome; 17. Any female subject who has a definitely or possibly positive pregnancy test result prior to vaccination or who is lactating; 18. As a result of the medical screening process, the Investigator considers the subject not suitable for the study.

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: MT-2766 High dose (3.75 µg)<br> | Biological: MT-2766 High dose (3.75 µg)<br>* Subjects will receive two doses of MT-2766 high dose (3.75 µg) given 21 days apart into the deltoid region of the alternating arm (each arm will be injected once)<br>* Other names: CoVLP, AS03 adjuvant;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subjects will receive two doses of placebo given 21 days apart into the deltoid region of the alternating arm (each arm will be injected once)<br>|
| Experimental: MT-2766 Low dose<br> | Biological: MT-2766 Low dose<br>* Subjects will receive two doses of MT-2766 low dose given 21 days apart into the deltoid region of the alternating arm (each arm will be injected once)<br>* Other names: CoVLP, AS03 adjuvant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Immediate Adverse Events (AEs) According to Severity, and Investigator-assessed Causality | Immediate AEs are defined as any solicited AEs and unsolicited AEs occurring within 30 minutes after vaccination. The causal relationship of all solicited AEs to investigational product was analyzed as related. | Within 30 minutes after each vaccination | 
| Percentage of Participants With Solicited AEs According to Severity | Solicited AEs are defined the following; (i) local AEs (injection site erythema, injection site swelling, injection site induration, and injection site pain) and (ii) systemic AEs (fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck)． | Within 7 days after each vaccination | 
| Percentage of Participants With Unsolicited AEs According to Severity, and Investigator-assessed Causality |  | Within 21 days after each vaccination | 
| Percentage of Participants With Serious AEs (SAEs), Medically Attended AEs (MAAEs), AEs Leading to Withdrawal, AEs of Special Interest (AESIs), and Deaths | AESIs include vaccine-associated enhanced diseases, hypersensitivity reactions, and potential immune-mediated diseases | Within 21 days after each vaccination | 
| SARS-CoV-2 Neutralizing Antibody (Nab) Responses: GMT | Geometric mean neutralizing antibody titer (GMT) | Day 0 (before 1st vaccination), Day 21 (21 days after 1st vaccination and before 2nd vaccination), and Day 42 (21 days after 2nd vaccination) | 
| SARS-CoV-2 Neutralizing Antibody (Nab) Responses: GMFR | Geometric mean fold rise (GMFR) is defined as the ratio of geometric mean antibody titer (GMT) based on that of Day 0 (i.e. Day 21/Day 0 and Day 42/Day 0). | Day 21 (21 days after 1st vaccination and before 2nd vaccination), and Day 42 (21 days after 2nd vaccination) | 
| SARS-CoV-2 Neutralizing Antibody (Nab) Responses | Seroconversion (SC) rate. SC rate is defined as the proportion of subjects achieving SC in the analysis set i.e. subjects with: For subjects with detectable Nab titer at Day 0 (i.e. baseline Nab titer ≥10): a ≥ 4-fold increase in Nab titers between Day 0 and Day 21/42, respectively. For subjects with undetectable Nab titer at Day 0 (i.e. baseline Nab titer < 10): Nab titer of ≥ 40 on Day 21/42, respectively. | Day 0 (before 1st vaccination), Day 21 (21 days after 1st vaccination and before 2nd vaccination), and Day 42 (21 days after 2nd vaccination) | 
| SARS-CoV-2-specific T Helper 1 (Th1) Cell-mediated Immune (CMI) Responses | Using the interferon-γ enzyme-linked immunospot (ELISpot) assay. Unit of Measure: Spot-Forming Cell (SFC)/10^6 Peripheral Blood Mononuclear Cells (PBMC) | Day 0 (before 1st vaccination), Day 21 (21 days after 1st vaccination and before 2nd vaccination), and Day 42 (21 days after 2nd vaccination) | 
| SARS-CoV-2-specific T Helper 2 (Th2) CMI Responses | Using the interleukin-4 ELISpot assay | Day 0 (before 1st vaccination), Day 21 (21 days after 1st vaccination and before 2nd vaccination), and Day 42 (21 days after 2nd vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Serious AEs (SAEs), Medically Attended AEs (MAAEs), AEs Leading to Withdrawal, AEs of Special Interest (AESIs), and Deaths | AESIs include vaccine-associated enhanced diseases, hypersensitivity reactions, and potential immune-mediated diseases. | Day 0 (after 1st vaccination) to end of study, on average the study duration by the termination is 334 days. | 
| SARS-CoV-2 Neutralizing Antibody (Nab) Responses: GMT | Geometric mean neutralizing antibody titer (GMT) | Day 128 and Day 201 | 
| SARS-CoV-2 Neutralizing Antibody (Nab) Responses: GMFR | Geometric mean fold rise (GMFR) | Day 128 and Day 201 | 
| Seroconversion (SC) Rate of SARS-CoV-2 Neutralizing Antibody | SC rate is defined as the proportion of subjects achieving SC in the analysis set i.e. subjects with: For subjects with detectable Nab titer at Day 0 (i.e. baseline Nab titer ≥10): a ≥ 4-fold increase in Nab titers between Day 0 and Day 128/201, respectively. For subjects with undetectable Nab titer at Day 0 (i.e. baseline Nab titer < 10): Nab titer of ≥ 40 on Day 128/201, respectively. | Day 128 and Day 201 | 
| SARS-CoV-2-specific T Helper 1 (Th1) Cell-mediated Immune (CMI) Responses | Using the interferon-γ enzyme-linked immunospot (ELISpot) assay. | Days 201 | 
| SARS-CoV-2-specific T Helper 2 (Th2) CMI Responses | Using the interleukin-4 ELISpot assay | Days 201 | 
| SARS-CoV-2-specific Antibody Responses (Total IgG): GMT | Geometric mean neutralizing antibody titer (GMT) | Day 0，Day 21，Day 42，Day 128 and Day 201 | 
| SARS-CoV-2-specific Antibody Responses (Total IgG): GMFR | Geometric mean fold rise (GMFR) | Day 0，Day 21，Day 42，Day 128 and Day 201 | 
| Seroconversion (SC) Rate of SARS-CoV-2-specific Antibody Responses (Total IgG): | SC rate is defined as the proportion of subjects achieving SC in the analysis set i.e. subjects with: For subjects with detectable Nab titer at Day 0 (i.e. baseline Nab titer ≥10): a ≥ 4-fold increase in Nab titers between Day 0 and Day 21/42/128/201, respectively. For subjects with undetectable Nab titer at Day 0 (i.e. baseline Nab titer < 10): Nab titer of ≥ 40 on Day 21/42, respectively. | Day 0，Day 21，Day 42，Day 128 and Day 201 |