Phase Ⅱ and Ⅲ Trial of a SARS-CoV-2 Vaccine LYB001

Study Overview
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Brief Summary
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The phase Ⅱ trial adopts a randomized, double-blind, placebo-controlled design to evaluate the immunogenicity and safety profile of LYB001 in healthy adults aged 18 years and older. This Phase III study adopts a single-arm, open-label design to evaluate the expanded safety of LYB001 in healthy subjects 18 years of age and older. The study vaccine will be administered IM at upper arm deltoid as a three-dose regimen with 28d interval on day 0, 28, 56. The phase Ⅱ trial will be carried out in an age-sequential enrolment manner: A DSMB meeting will be held after the completion of the 7-day safety observation following each vaccination of high-dose LYB001 or placebo in participants aged 18-59 years in phase Ⅰ trial. Thereafter, the DSMB will recommend whether to initiate enrollment of younger adult participants in the Phase II trial based on the findings, who will receive low dose (25μg), high dose (50μg) LYB001 or placebo at a ratio of 3:3:1. A DSMB meeting will be held after the completion of the 7-day safety observation following each vaccination of high-dose LYB001 or placebo in participants aged ≥60 year in phase Ⅰ trial. Thereafter, the DSMB will recommend whether to initiate enrollment of older adult participants in the Phase II trial based on the findings, who will receive low dose (25μg), high dose (50μg) LYB001 or placebo at a ratio of 3:3:1. The phase Ⅱ trial will be ended after all participants completed 360-day safety observation following the 3rd dose of vaccination. Phase III trial (the expanded safety study): After completion of the 7-day safety observation following the first immunization of all cohorts in the Phase II trial, a DSMB meeting will be held to recommend whether to initiate enrollment of participants in the Phase III trial. A total of 1200 subjects will be enrolled in younger adult and older adults, with older adults accounting for ≥20% of the population, and appropriate doses will be determined based on the results of early clinical trials. The phase III trial will be ended after all participants completed 360-day safety observation following the 3rd dose of vaccination.

Official Title
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Immunogenicity and Safety of a SARS-CoV-2 Vaccine LYB001 in Healthy Adults: a Randomized, Double Blinded, Placebo-controlled Phase Ⅱ Trial and a Single-arm, Open-label Phase Ⅲ Trial for Extended Safety

Conditions
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COVID-19

Intervention / Treatment
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* Biological: LYB001
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects aged 18 years and older; 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. 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: Abnormal results of laboratory screening tests which was clinically significant judged by clinicians; Abnormal vital signs with clinical significance at screening, with systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, or axillary body temperature ≥ 37.3°C; Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients; History of human coronavirus infection/diseases, such as severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS); History of COVID-19, or history of close contact with confirmed/suspected COVID-19 patients, or positive results for either SARS-CoV-2 nucleic acid or antibody tests (IgG and IgM) at screening; Administration of antipyretics or painkillers within 24 hours prior to vaccination; Receipt of any COVID-19 vaccine, live attenuated vaccine within 28 days prior to vaccination and other vaccines, such as subunit and inactived vaccine within 14 days prior to vaccination; Receipt of blood or blood-related products, including immunoglobulins, within 3 months prior to vaccination; or any planned use during the study period. Subjects with the following diseases: Any acute diseases or acute attacks of chronic diseases within 7 days prior to enrolment； Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.； 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； Currently suffering from or previously diagnosed with infectious diseases, positive screening results for hepatitis B surface antigen, hepatitis C antibody, treponema pallidum antibody, human immunodeficiency virus antibody (Pathogen screening test will be only conducted in phase Ⅱ)； History or family history of neurological disorders (convulsions, epilepsy, encephalopathy, etc.) or psychiatric disorders； Asplenia, or functional asplenia； Presence of severe, uncontrollable or hospitalization indicated cardiovascular diseases, diabetes, neurological diseases (e.g., Guillain-Barre syndrome), blood and lymphatic diseases, immune diseases, liver and kidney diseases, respiratory diseases, metabolic and skeletal diseases, or malignant tumors; 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; History of a major surgery, per the investigator's judgment, within 12 weeks before vaccination, or not achieving full recovery after surgery, or any planned major surgery during the study; Pregnant or lactating females, or those who plan to become pregnant during the study period; Having participated or being participating in COVID-19 related clinical trials, and those being 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.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low-dose LYB001 in participants aged 18-59 years<br>25μg/0.5ml/Vial. Intramuscular injection (IM) at upper arm deltoid on day 0, 28, 56. | Biological: LYB001<br>* The investigational vaccine, with its antigen consisting of receptor-binding domain (RBD) from SARS-CoV-2 and virus-like particle (VLP) vector, adjuvanted with aluminum hydroxide.<br>|
| Experimental: high-dose LYB001 in participants aged 18-59 years<br>50μg/0.5ml/Vial. Intramuscular injection (IM) at upper arm deltoid on day 0, 28, 56. | Biological: LYB001<br>* The investigational vaccine, with its antigen consisting of receptor-binding domain (RBD) from SARS-CoV-2 and virus-like particle (VLP) vector, adjuvanted with aluminum hydroxide.<br>|
| Placebo Comparator: placebo in participants aged 18-59 years<br>intramuscular injection (IM) at upper arm deltoid on day 0, 28, 56. | Biological: Placebo<br>* Aluminum hydroxide<br>|
| Experimental: low-dose LYB001 in participants aged over 60 years<br>25μg/0.5ml/Vial. Intramuscular injection (IM) at upper arm deltoid on day 0, 28, 56. | Biological: LYB001<br>* The investigational vaccine, with its antigen consisting of receptor-binding domain (RBD) from SARS-CoV-2 and virus-like particle (VLP) vector, adjuvanted with aluminum hydroxide.<br>|
| Experimental: high-dose LYB001 in participants aged over 60 years<br>50μg/0.5ml/Vial. Intramuscular injection (IM) at upper arm deltoid on day 0, 28, 56. | Biological: LYB001<br>* The investigational vaccine, with its antigen consisting of receptor-binding domain (RBD) from SARS-CoV-2 and virus-like particle (VLP) vector, adjuvanted with aluminum hydroxide.<br>|
| Placebo Comparator: placebo in participants aged over 60 years<br>intramuscular injection (IM) at upper arm deltoid on day 0, 28, 56. | Biological: Placebo<br>* Aluminum hydroxide<br>|
| Experimental: LYB001 in participants aged over 18 years<br>intramuscular injection (IM) at upper arm deltoid on day 0, 28, 56. | Biological: LYB001<br>* The investigational vaccine, with its antigen consisting of receptor-binding domain (RBD) from SARS-CoV-2 and virus-like particle (VLP) vector, adjuvanted with aluminum hydroxide.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutralizing antibody against SARS-CoV-2 wild type and variants of concern (VOCs) | Neutralizing antibody against SARS-CoV-2 wild type and variants of concern (VOCs) | Change from Baseline at 14 days post dose 3 | 
| SRAS-CoV-2 S protein-binding antibodies | SRAS-CoV-2 S protein-binding antibodies | Change from Baseline at 14 days post dose 3 | 
| Neutralizing antibody against SARS-CoV-2 wild type and variants of concern (VOCs) | Neutralizing antibody against SARS-CoV-2 wild type and variants of concern (VOCs) | Change from Baseline at 28 days post dose 3 | 
| SRAS-CoV-2 S protein-binding antibodies | SRAS-CoV-2 S protein-binding antibodies | Change from Baseline at 28 days post dose 3 | 
| Adverse events (AEs) | Immediate adverse events (AEs) within 30 minutes after each vaccination, solicited local and systemic AEs for within 7 days and unsolicited AEs within 28 days following each vaccination | 28 days after each dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious adverse events (SAEs) | Serious adverse events (SAEs) throughout the study | 360 days after first dose | 
| Neutralizing antibody against SARS-CoV-2 wild type and variants of concern (VOCs) | Neutralizing antibody against SARS-CoV-2 wild type and variants of concern (VOCs) | 3 months post dose 3 | 
| Neutralizing antibody against SARS-CoV-2 wild type and variants of concern (VOCs) | Neutralizing antibody against SARS-CoV-2 wild type and variants of concern (VOCs) | 6 months post dose 3 | 
| Neutralizing antibody against SARS-CoV-2 wild type and variants of concern (VOCs) | Neutralizing antibody against SARS-CoV-2 wild type and variants of concern (VOCs) | 12 months post dose 3 | 
| SRAS-CoV-2 S protein-binding antibodies | SRAS-CoV-2 S protein-binding antibodies | 3 months post dose 3 | 
| SRAS-CoV-2 S protein-binding antibodies | SRAS-CoV-2 S protein-binding antibodies | 6 months post dose 3 | 
| SRAS-CoV-2 S protein-binding antibodies | SRAS-CoV-2 S protein-binding antibodies | 12 months post dose 3 |