Safety immunogenicity study of MT-2766 in Japanese adults (COVID-19)

JRCT ID: jRCT2051210093

Registered date:28/09/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: COVID-19
• Date of first enrollment: 02/10/2021
• Target sample size: 145
• Study type: Interventional
• Intervention(s): Two doses (Day 0 and Day 21) of MT-2766 (including CoVLP and AS03) High dose, MT-2766 (including CoVLP and AS03) Low dose or Placebo.

Outcome(s)

Primary Outcome

Safety:
1. The incidences, severity, and investigator-assessed causality of immediate adverse events (AEs) that occur within 30 minutes of first (Day 0) and second (Day 21) injections.
2. The incidences and severity of the following solicited AEs that develop within 7 days of first (Day 0) and second (Day 21) injections: (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).
3. The incidences, severity, and investigator-assessed causality of unsolicited AEs that develop within 21 days of first (Day 0) and second (Day 21) injections.
4. The incidences of serious AEs (SAEs), medically attended AEs (MAAEs), AEs leading to withdrawal, AEs of special interest (AESIs), and deaths up to 21 days following first (Day 0) and second (Day 21) injections. AESIs include vaccine-associated enhanced diseases (VAED), hypersensitivity reactions, and potential immune-mediated diseases (pIMDs)
Immunogenicity:
1. SARS-CoV-2 neutralizing antibody (Nab) responses will be analyzed on Days 0, 21, and 42 using the following parameters: geometric mean antibody titer (GMT), seroconversion (SC) rate, and geometric mean fold rise (GMFR);
2. SARS-CoV-2-specific T helper 1 (Th1) cell-mediated immune (CMI) responses will be measured on Days 0, 21, and 42 using the interferon (IFN)-gamma enzyme-linked immunospot (ELISpot) assay;
3. SARS-CoV-2-specific T helper 2 (Th2) CMI responses will be measured on Days 0, 21, and 42 using the interleukin (IL)-4 ELISpot assay.

Secondary Outcome

Safety:
1. The incidences of SAEs, MAAEs, AEs leading to withdrawal, AESIs, and deaths from Day 43 to Day 201;
2. The incidences of SAEs, MAAEs, AEs leading to withdrawal, AESIs, and deaths from Day 202 to Day 386;
3. The numbers and percentages of subjects with normal and abnormal urine, hematological, and biochemical test results within three days of first (Day 0) and second (Day 21) injections.
Immunogenicity:
1. Persistence of SARS-CoV-2 Nab response will be assessed on Days 128, 201, and 386 using the following parameters: GMT, SC rate, and GMFR.
2. SARS-CoV-2-specific antibody responses will be measured on Days 0, 21, and 42 based on the total immunoglobulin G (IgG) level, and the persistence of these antibodies will be analyzed on Days 128, 201, and 386 using the following parameters: GMT, SC rate, and GMFR;
3. SARS-CoV-2-specific Th1 CMI responses will be measured on Days 201 and 386 using the IFN-gamma ELISpot assay;
4. SARS-CoV-2-specific Th2 CMI responses will be measured on Days 201 and 386 using the IL-4 ELISpot assay;

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include 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:
1. 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;
2. At the Screening visit (Visit 1), Japanese male and female subjects must be >=20 years of age;
3. At the Screening visit (Visit 1) and 1st vaccination visit (Visit 2), subject must have a body mass index (BMI) of >=18.5 kg/m2 and <30 kg/m2;
4. 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;
5. 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);
6. 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);
7. Subjects must be non-institutionalized (e.g. not living in rehabilitation centers or old-age homes; subjects who can live independently are acceptable);
8. 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.

Exclude 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:
1. 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-Barre 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.

Related Information

• Primary Sponsor: Kondo Kazuoki
• Secondary ID(s): NCT05065619