The study will be conducted in two phases using a randomized, double-blind,placebo-controlled design. A phase II trial will be initiated to assess the safety ofLYB001 as booster shots, and then proceed to a phase III trial to assess the vaccineefficacy (VE) of LYB001 against COVID-19 after an acceptable safety profile, per thejudgement of Data and Safety Monitoring Board (DSMB), within 28 days after booster in thephase Ⅱ trial is assessed. After collection of 155 COVID-19 cases, all participants willget unblinded. Participants assigned to the placebo group can choose to receive LYB001vaccine at their own discretion.Phase II stage:The purpose of phase Ⅱ study is to assess the safety of healthy subjects aged 18 yearsand older who have completed two-dose or three-dose inactivated COVID-19 vaccine for 6-18months. About 200 age s-stratified subjects aged over 18 years will be randomly assignedto receive the LYB001 or placebo in a 1:1 ratio in the deltoid muscle of the upper arm.The Phase III study will be initiated after the DSMB confirm that all subjects in PhaseII experience acceptable safety profile within 28 days after booster. All subjects inPhase II trial will be required to complete efficacy follow-ups for 12 months along withsafety observation, and will be included in the Phase III efficacy analysis set (Phase IIdata will eventually be combined with Phase III data for statistical analysis, includingefficacy and safety data).Phase III stage:A total of 17800 participants aged 18 years and older who have completed two-dose orthree-dose inactivated COVID-19 vaccine for 6-18 months. The participants will berandomly assigned to the LYB001 booster or placebo booster group in 1:1 ratio accordingstratification factors of study center and age (18-59 years vs. ≥60 years) , withparticipants aged ≥ 60 years accounting for over 20 percent of total population.After booster vaccination, all subjects will be evaluated for protective efficacy andsafety, and 1000 subjects (800 subjects aged 18-59 years, and 200 subjects aged ≥60years) will be enrolled in the subgroup for immunogenicity evaluation (LYB001:Placebo=1:1).All subjects will be followed up to 12 months after booster vaccination. The entireclinical study will be completed after the pre-defined COVID-19 cases has been achievedand each participant has completed 12-month follow-ups.
Not Provided
Biological: LYB001
The antigen consists of receptor-binding domain (RBD) from wild-type SARS-CoV-2
displaying on virus-like particle (VLP) vector, adjuvanted with aluminium hydroxide.
Biological: Placebo
Aluminium hydroxide adjuvant
Inclusion Criteria:
- Healthy subjects aged 18 years and older, including both males and females;
- Subjects who agree to participate in this clinical trial voluntarily and sign the
informed consent form, are capable of providing valid identification, understanding
and complying with the requirements of the clinical protocol.
- Subjects who have been vaccinated with two-dose or three-dose inactivated COVID-19
vaccine for6-18 months (including boundary values).
- For female participants of childbearing potential, effective contraception measures
should be used within 2 weeks prior to participation in this study and the results
of pregnancy test is required to be negative. Participants should voluntarily agree
to use effective contraceptive measures from the time of signing the informed
consent form to the end of the study (effective contraceptive measures including
oral contraceptives (excluding emergency contraceptives), injectable or implantable
contraceptives, sustained-release topical contraceptives, hormonal patches,
intrauterine device, sterilization, abstinence, condoms (for males), diaphragms,
cervical caps, etc.).
Exclusion Criteria:
- Receipt of any COVID-19 prophylactic medication other than inactivated COVID-19
vaccine (e.g., receipt history of any approved or under developing COVID-19
vaccines, or other COVID-19 prophylactic medication, etc.), or previous vaccination
history other than other than two- or three-dose inactivated COVID-19 vaccination;
- Systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg (for
subjects with poorly controlled blood pressure), or axillary body temperature ≥
37.3°C prior to enrolment;
- Known allergy, or history of anaphylaxis or other serious adverse reactions to
vaccines or their excipients;
- History of severe acute respiratory syndrome (SARS) or Middle East respiratory
syndrome (MERS);
- History of COVID-19, or positive results for SARS-CoV-2 nucleic acid or antigen
tests at screening;
- Receipt of any live attenuated vaccine within 28 days prior to vaccination, and
other vaccines such as subunit and inactivated vaccine within 14 days prior to
vaccination;
- Receipt of blood or blood-related products, including immunoglobulins, monoclonal
antibodies, within 3 months prior to vaccination; or any planned use during the
study period.
- Subjects with the following diseases:
1. Any acute diseases or acute attacks of chronic diseases within 7 days prior to
enrolment；
2. Congenital malformations or developmental disorders, genetic defects, severe
malnutrition, etc.；
3. Congenital or acquired immunodeficiency or autoimmune disease, or long-term
receipt (>14 consecutive days) of glucocorticoid (reference value for dose: ≥20
mg/day prednisone or equivalent) or other immunosuppressive agents within the
past 6 months, with exception of inhaled or topical steroids, or short-term use
(≤14 consecutive days) of oral corticosteroids；
4. Currently suffering from or diagnosed with infectious diseases, such as
hepatitis B, hepatitis C, syphilis, AIDS etc.；
5. History or family history of neurological disorders (convulsions, epilepsy,
encephalopathy, etc.) or psychiatric disorders；
6. Asplenia, or functional asplenia；
7. Presence of severe, uncontrollable or hospitalized cardiovascular diseases,
endocrine diseases, blood and lymphatic diseases, immune diseases, liver and
kidney diseases, respiratory diseases, metabolic and skeletal diseases, or
malignant tumors;
8. Contraindications to IM injections and blood draws, such as coagulation
disorders, thrombotic or bleeding disorders, or conditions that needs
continuous anticoagulant usage.
- Drug or alcohol abuse (alcohol intake ≥ 14 units per week) which in the
investigator's opinion would compromise the participant's safety or compliance with
the study procedures;
- Pregnant or lactating females;
- Having participated or participating in COVID-19 related clinical trials, and those
participating or planning to participate in other clinical trials during the study
period;
- Presence of any underlying disease or condition which, in the opinion of the
investigator, may place the subject at unacceptable risk, is unable to meet the
requirements of the protocol, or interfere with the assessment of vaccine response.
Not Provided
Not Provided