預防2019冠狀病毒病(COVID-19)

安全性、耐受性、免疫原性與療效之探索

COVID-19的S蛋白片段 (fragment)

劑量,0.5

Phase IIa:
 Immunogenicity
– SARS-CoV-2 neutralizing tiers
– Geometric mean titers (GMT), geometric mean increase (GMI) and seroconversion rate (SCR) at the baseline (V0) and the subsequent scheduled visits after the vaccination (V2, V3, FU1, FU2, and FU3)
– SARS-CoV-2 specific IgG antibody
– Geometric mean titers, geometric mean increase (GMI) and seroconversion rate (SCR) between the baseline (V0) and the subsequent scheduled visits after the vaccination (V2, V3, FU1, FU2, and FU3)
 Safety profile of AdimrSC-2f vaccine:
– Adverse events (AEs):
(1) Incidence of solicited local and systemic AEs
(2) Incidence of AEs
(3) Incidence of serious adverse events (SAEs)
(4) Incidence of discontinuation from study intervention due to AEs
(5) Incidence of Grades 3 and 4 AEs
(6) Incidence of vaccine-related AEs
– Changes in clinical and laboratory evaluations
 To determine the optimal dose for Phase IIb study based on SCR by neutralizing antibody titer and safety profiles of AdimrSC-2f vaccine

Phase IIb:
1. Primary endpoints:
 Percentage of neutralizing antibody titer SCR at FU1 compared to the baseline (V0)

2. Secondary endpoints:
 Immune Responses:
– SCR between the baseline (V0) and the subsequent scheduled visits after the vaccination (V2, V3, FU1, FU2, and FU3)
– GMT of neutralizing antibody for SARS-CoV-2 at the baseline (V0) and the subsequent scheduled visits after the vaccination (V2, V3, FU1, FU2, and FU3)
– GMI between the baseline (V0) and the subsequent scheduled visits after the vaccination (V2, V3, FU1, FU2, and FU3)
– GMT of SARS-CoV-2 specific IgG antibody at the baseline (V0) and the subsequent scheduled visits after the vaccination (V2, V3, FU1, FU2, and FU3)
– GMI and SCR of SARS-CoV-2 specific IgG antibody between the baseline (V0) and the subsequent scheduled visits after the vaccination (V2, V3, FU1, FU2, and FU3)
 Safety:
– Adverse events (AEs):
(1) Incidence of solicited local and systemic AEs
(2) Incidence of AEs
(3) Incidence of SAEs
(4) Incidence of discontinuation from study intervention due to AEs
(5) Incidence of Grades 3 and 4 AEs.
(6) Incidence of vaccine-related AEs
– Changes in clinical and laboratory evaluations
 The lot-to-lot consistency in 3 independent clinical lots of AdimrSC-2f vaccine by comparing the GMT at 4 weeks after the last dose of vaccination. The 95% confidence intervals (CIs) between lots will be within the margin of 0.5 to 2.
Note: The last dose will be the 2nd or 3rd vaccination depending on the dosing regimen selected for the Phase IIb.
 The GMT levels, GMI, and SCR in different age groups
 The efficacy of AdimrSC-2f vaccine to prevent the first occurrence of COVID-19 infection from 14 days after receiving the last dose of vaccination
Note: The last dose will be the 2nd or 3rd vaccination depending on the dosing regimen selected for the Phase IIb.
COVID-19 infection case is defined that the subject who has at least one nasopharyngeal swab or nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR), occurring from 14 days after receiving the last dose of vaccination, and also has one or more of following symptoms:
• fever or chills
• cough
• shortness of breath or difficulty breathing
• fatigue
• muscle or body aches
• headache
• new loss of taste or smell
• sore throat
• congestion or runny nose
• nausea or vomiting
• diarrhea
 The efficacy of AdimrSC-2f vaccine to prevent the first occurrence of severe COVID-19 infection from 14 days after receiving the last dose of vaccination
Note: The last dose will be the 2nd or 3rd vaccination depending on the dosing regimen selected for the Phase IIb.
Severe COVID-19 infection case is defined as below:
Subject who has at least one positive result for SARS-CoV-2 by standard RT-PCR using nasopharyngeal swab or nasal swab (or respiratory sample, if hospitalized), occurring from 14 days after receiving the last dose of vaccination, and also has any one of following clinical signs:
(1) Respiratory rate  30 breaths per minute, heart rate  125 beats per minute, saturation of oxygen (SpO2)  93% on room air at sea level or PaO2/FiO2  300 mmHg
(2) Respiratory failure
(3) Evidence of shock
(4) Significant acute renal, hepatic or neurologic dysfunction
(5) Admission to an intensive care unit (ICU)
(6) Death
Note:
i. Respiratory failure defined based on resource utilization requiring at least one of the followings:
Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates  20 L/min with fraction of delivered oxygen  0.5), noninvasive positive pressure ventilation, extracorporeal membrane oxygenation (ECMO), or clinical diagnosis of respiratory failure (ie, clinical need for one of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation).
ii. Shock is defined by systolic blood pressure  90 mmHg, or diastolic blood pressure  60 mmHg or requiring vasopressors.

1. Main inclusion criteria:
Subjects who meet ALL inclusion criteria will be included.
Phase IIa/IIb:
1) Adults aged ≥ 20 years old.
2) Healthy subjects or subjects with pre-existing medical conditions who are in stable condition. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before randomization (V1).
3) Female subject with childbearing potential must have negative result in urine pregnancy test at the screening visit (V0) and negative results in urine strip test/urine stick test before randomization (V1).
4) Female subject with childbearing potential must be willing to implement adequate, highly effective contraceptive measure during the study period. Effective birth control includes:
a. Intrauterine device plus one barrier method
b. Oral, implantable, or injectable contraceptives plus one barrier method; or
c. Two barrier methods (Effective barrier methods are male or female condoms, diaphragms, or spermicides [creams or gels that contain a chemical to kill sperm]).
Women who have been surgically sterilized or have been free from menses for ≥ 1 year are considered as non-childbearing potential.
5) Subject who is physically and mentally capable of participating the study and is willing to comply with to study procedures.
6) Subject who provides informed consent after receiving a detailed explanation of study procedures.

2. Main exclusion criteria:
Subjects who meet ANY exclusion criteria will be excluded. The first four items of the criteria are only applicable to Phase IIa.
1) Subjects with known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV).
2) Subject with the following active disease:
(a) Hypertension
(b) Diabetes mellitus
(c) Chronic pulmonary disease
(d) Asthma
(e) Chronic liver disease
(f) Clinically significant cardiovascular disease such as arrhythmia, coronary artery disease or heart failure
3) Subject’s abnormal electrocardiogram (ECG) or laboratory test results with clinical significance as judged by the investigator.
4) Subject with positive test result in COVID-19 antigen rapid test at the screening visit (V0).

Phase IIa/IIb:
5) Subject with previous laboratory-confirmed SARS-CoV-2 infection with clinical symptoms
6) Subject with influenza-like illness as defined by any of the following symptoms at the screening visit (V0) or before randomization (V1): fever (tympanic temperature ≥ 38℃), dry cough, headache, fatigue, respiratory sputum production (phlegm), dysgeusia, anosmia, shortness of breath, muscle and joint pain, or sore throat.
7) Subject with history of severe adverse reaction associated with a vaccine or severe allergic reaction to AdimrSC-2f or its components, or aluminum.
8) Subject with any confirmed or suspected abnormal immune function, immunosuppressive, or immunodeficiency or received any immunosuppressants or immunomodulators within 180 days prior to the randomization (V1).
9) Subject with family history of immune disorders after the proper test per the investigator′s discretion
10) Subject with personal or family history of Guillain-Barré Syndrome.
11) Female subject who is pregnant or lactating at the screening visit or plans to be pregnant during the study period.
12) Subject who received any vaccine (live, inactivated, or bacterial) within 30 days prior to the screening visit (V0).
13) Subject who received any blood/plasma products or immunoglobulin within 90 days prior to the screening visit (V0).
14) Subject who has received any investigational coronavirus vaccine or has received any medications intended to prevent COVID-19 or plan simultaneous participation in another interventional study to prevent or treat COVID-19.
15) Subject who treated with an investigational drug or device or have participated in a clinical study within 90 days prior to the screening visit (V0) or is planning to do so during the study period.
16) Subject who had bleeding diathesis or condition associated with prolonged bleeding as judged by the investigator.
17) Subject who had donated ≥ 250 mL of blood product within 28 days prior to the screening visit (V0).
18) Subject who is not suitable to participate in this study as judged by the investigator.

3. Discontinuation of study intervention:
Subjects may permanently discontinue from the study intervention due to the following reasons:
(1) If subject develops fever  39℃, neurological reaction (≥ Grade 2), or general allergic reaction (≥ Grade 2) within 48 hours after the 1st dose of vaccination, he/she should not receive the 2nd dose or more vaccination.
(2) Pregnancy in female subjects; if the female subject is pregnant within 30 days after the vaccination, she will be followed for pregnancy outcomes, including miscarriage, stillbirth, or congenital anomalies.
(3) Unsuspected severe AEs (≥ Grade 3) that occur after the vaccination and are considered to be related to the study product by the investigator.
(4) AEs or SAEs that, in the judgment of the investigator, require to discontinue the study intervention due to its nature, severity, or required treatment, regardless of the causal relationship to the study product.
(5) Uses prohibited treatments/products.
(6) If the subject has confirmed COVID-19 infection with positive results for SARS-CoV-2 by standard RT-PCR during the study period, the subject must not receive additional doses of vaccine but will be encouraged to continue the study participation for safety monitoring. If infection with COVID-19 is suspected on the day of vaccination or prior to the day of vaccination, further administration of vaccine must be withheld until COVID-19 test results are available.
Note that discontinuation of the study product does not represent withdrawal from the study. The subject will remain in the study and complete the following visits until FU3 (48 weeks ± 14 days after the last vaccination). Reasons for missing the vacciantion will be collected and recorded in the electronic case report form (eCRF).

4. Withdrawal from the study:
Subjects may be withdrawn from the study due to any of the following reasons:
(1) Withdraw consent
(2) Lost to follow-up
(3) Death
(4) Withdraw consent due to adverse events/serious adverse events
(5) Withdraw consent due to pregnancy (only for female subject)
(6) Study termination by Sponsor
If the subject withdraws from the study, no further evaluations should be performed and no additional data will be collected. The Sponsor may retain and continue to use any data collected before withdrawal from the study. Reasons for withdrawn from the study will be collected and recorded in the eCRF.
Note that if the subject withdraws from the study due to the AE or SAE, the investigator will follow up the subject until the AE/SAE is resolved or under the stable condition per the investigator’s discretion.
If the subject repeatedly fails to return for the scheduled clinic visits or to be contacted for safety phone visits, he/she will be considered lost to follow-up. Before the subject is identified as lost to follow-up, the site should make all reasonable efforts to contact the subject. At least 3 attempts via telephone contact, mails or other ways must be documented.
Subjects prematurely discontinued from the study intervention or withdrawn from the study will not be replaced.

1. Main inclusion criteria:
Subjects who meet ALL inclusion criteria will be included.
Phase IIa/IIb:
1) Adults aged ≥ 20 years old.
2) Healthy subjects or subjects with pre-existing medical conditions who are in stable condition. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before randomization (V1).
3) Female subject with childbearing potential must have negative result in urine pregnancy test at the screening visit (V0) and negative results in urine strip test/urine stick test before randomization (V1).
4) Female subject with childbearing potential must be willing to implement adequate, highly effective contraceptive measure during the study period. Effective birth control includes:
a. Intrauterine device plus one barrier method
b. Oral, implantable, or injectable contraceptives plus one barrier method; or
c. Two barrier methods (Effective barrier methods are male or female condoms, diaphragms, or spermicides [creams or gels that contain a chemical to kill sperm]).
Women who have been surgically sterilized or have been free from menses for ≥ 1 year are considered as non-childbearing potential.
5) Subject who is physically and mentally capable of participating the study and is willing to comply with to study procedures.
6) Subject who provides informed consent after receiving a detailed explanation of study procedures.

2. Main exclusion criteria:
Subjects who meet ANY exclusion criteria will be excluded. The first four items of the criteria are only applicable to Phase IIa.
1) Subjects with known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV).
2) Subject with the following active disease:
(a) Hypertension
(b) Diabetes mellitus
(c) Chronic pulmonary disease
(d) Asthma
(e) Chronic liver disease
(f) Clinically significant cardiovascular disease such as arrhythmia, coronary artery disease or heart failure
3) Subject’s abnormal electrocardiogram (ECG) or laboratory test results with clinical significance as judged by the investigator.
4) Subject with positive test result in COVID-19 antigen rapid test at the screening visit (V0).

Phase IIa/IIb:
5) Subject with previous laboratory-confirmed SARS-CoV-2 infection with clinical symptoms
6) Subject with influenza-like illness as defined by any of the following symptoms at the screening visit (V0) or before randomization (V1): fever (tympanic temperature ≥ 38℃), dry cough, headache, fatigue, respiratory sputum production (phlegm), dysgeusia, anosmia, shortness of breath, muscle and joint pain, or sore throat.
7) Subject with history of severe adverse reaction associated with a vaccine or severe allergic reaction to AdimrSC-2f or its components, or aluminum.
8) Subject with any confirmed or suspected abnormal immune function, immunosuppressive, or immunodeficiency or received any immunosuppressants or immunomodulators within 180 days prior to the randomization (V1).
9) Subject with family history of immune disorders after the proper test per the investigator′s discretion
10) Subject with personal or family history of Guillain-Barré Syndrome.
11) Female subject who is pregnant or lactating at the screening visit or plans to be pregnant during the study period.
12) Subject who received any vaccine (live, inactivated, or bacterial) within 30 days prior to the screening visit (V0).
13) Subject who received any blood/plasma products or immunoglobulin within 90 days prior to the screening visit (V0).
14) Subject who has received any investigational coronavirus vaccine or has received any medications intended to prevent COVID-19 or plan simultaneous participation in another interventional study to prevent or treat COVID-19.
15) Subject who treated with an investigational drug or device or have participated in a clinical study within 90 days prior to the screening visit (V0) or is planning to do so during the study period.
16) Subject who had bleeding diathesis or condition associated with prolonged bleeding as judged by the investigator.
17) Subject who had donated ≥ 250 mL of blood product within 28 days prior to the screening visit (V0).
18) Subject who is not suitable to participate in this study as judged by the investigator.

3. Discontinuation of study intervention:
Subjects may permanently discontinue from the study intervention due to the following reasons:
(1) If subject develops fever  39℃, neurological reaction (≥ Grade 2), or general allergic reaction (≥ Grade 2) within 48 hours after the 1st dose of vaccination, he/she should not receive the 2nd dose or more vaccination.
(2) Pregnancy in female subjects; if the female subject is pregnant within 30 days after the vaccination, she will be followed for pregnancy outcomes, including miscarriage, stillbirth, or congenital anomalies.
(3) Unsuspected severe AEs (≥ Grade 3) that occur after the vaccination and are considered to be related to the study product by the investigator.
(4) AEs or SAEs that, in the judgment of the investigator, require to discontinue the study intervention due to its nature, severity, or required treatment, regardless of the causal relationship to the study product.
(5) Uses prohibited treatments/products.
(6) If the subject has confirmed COVID-19 infection with positive results for SARS-CoV-2 by standard RT-PCR during the study period, the subject must not receive additional doses of vaccine but will be encouraged to continue the study participation for safety monitoring. If infection with COVID-19 is suspected on the day of vaccination or prior to the day of vaccination, further administration of vaccine must be withheld until COVID-19 test results are available.
Note that discontinuation of the study product does not represent withdrawal from the study. The subject will remain in the study and complete the following visits until FU3 (48 weeks ± 14 days after the last vaccination). Reasons for missing the vacciantion will be collected and recorded in the electronic case report form (eCRF).

4. Withdrawal from the study:
Subjects may be withdrawn from the study due to any of the following reasons:
(1) Withdraw consent
(2) Lost to follow-up
(3) Death
(4) Withdraw consent due to adverse events/serious adverse events
(5) Withdraw consent due to pregnancy (only for female subject)
(6) Study termination by Sponsor
If the subject withdraws from the study, no further evaluations should be performed and no additional data will be collected. The Sponsor may retain and continue to use any data collected before withdrawal from the study. Reasons for withdrawn from the study will be collected and recorded in the eCRF.
Note that if the subject withdraws from the study due to the AE or SAE, the investigator will follow up the subject until the AE/SAE is resolved or under the stable condition per the investigator’s discretion.
If the subject repeatedly fails to return for the scheduled clinic visits or to be contacted for safety phone visits, he/she will be considered lost to follow-up. Before the subject is identified as lost to follow-up, the site should make all reasonable efforts to contact the subject. At least 3 attempts via telephone contact, mails or other ways must be documented.
Subjects prematurely discontinued from the study intervention or withdrawn from the study will not be replaced.