Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) Phase III

Study Overview
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Brief Summary
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A Global, Multi-center, Randomized, Double-Blind, Placebo-Controlled, Phase III Clinical Study to Evaluate the Efficacy, Safety, and Immunogenicity of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) in Adults Aged 18 Years and Older

Detailed Description
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This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III clinical study. Approximately 22,500 participants aged 18 years and older will be enrolled in this study to evaluate the efficacy, safety and immunogenicity of recombinant SARS-CoV-2 fusion protein vaccine (code: V-01, hereinafter referred to as V-01). The eligible participants will be randomized in a 2:1 ratio into investigational vaccine group (V-01) and placebo group, with random stratification factors including 1) age (18-59 years vs ≥60 years); 2) gender (male vs female); and 3) whether or not being enrolled into immunogenicity subgroup (yes vs no). The participants will receive investigational vaccine V-01 or placebo on two doses schedule (one dose each on day 0 and 21, with +7 days' time window for the second dose).

Official Title
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A Global, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Phase III Clinical Study to Evaluate the Efficacy, Safety, and Immunogenicity of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) in Adults Aged 18 Years and Older

Conditions
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COVID-19 Pandemic

Intervention / Treatment
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* Biological: Recombinant SARS-CoV-2 fusion protein vaccine (V-01)
* Other: Blank Preparation of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participants can be enrolled only all of the following criteria are met: Voluntarily participate in this study and sign the informed consent form; Adults aged 18 years and older, male or female; According to the assessment of the investigator, the participant has a stable medical condition (which is defined as no significant changes in therapy or hospitalization caused by disease aggravation within 3 months before enrollment) and is able to and willing to follow the requirements of the protocol. Males of reproductive potential and females of child-bearing potential voluntarily agree to take effective and acceptable contraceptive methods from the signing of informed consent form to 12 months after full-course immunization; females of child-bearing potential have a negative pregnancy test at screening and at the day of vaccination. Exclusion Criteria: Participants meeting any of the following exclusion criteria will not be allowed to participate in this study: 1.History of previous COVID-19 infection; 2.Positive result for RT-PCR test in the screening period or specific antibody IgG or IgM meet the following criteria: If IgG is positive, the participant will be excluded regardless of the results of other indexes. If IgG is negative and IgM is positive, it will be determined whether or not to enroll such participant after the result of RT-PCR test is obtained; If both IgG and IgM are negative, the participant can be vaccinated without waiting for the RT-PCR test results. 3.History of severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), and other human coronavirus infections or diseases; 4.History of severe allergy to any vaccine, e.g., acute allergic reactions, urticaria, skin eczema, dyspnea, angioneurotic edema or abdominal pain etc., or be allergic to any components of V-01; 5.Any confirmed or suspected immunosuppression or immunodeficiency condition known from medical history, including human immunodeficiency virus (HIV) infection, asplenia; 6.Serious or uncontrolled cardiovascular diseases, nervous system disorders (e.g., Guillain-Barre syndrome), blood and lymphatic system disorders, immune system disorders, hepatorenal disorders, respiratory system disorders (e.g., active tuberculosis, pulmonary fibrosis), metabolic and skeletal systems disorders or malignant tumors (except for skin basal cell carcinoma or in situ carcinoma of uterine cervix that has been cured for more than 5 years); 7.Hereditary hemorrhagic tendency or coagulation dysfunction, or a history of thrombosis or hemorrhagic disease, or requirement of continuous use of anticoagulants; 8.Prior use of any medications to prevent COVID-19, e.g., use of antipyretics without pyrexia and any other symptoms; 9.A history of vaccination against SARS-CoV-2 (marketed or investigational); 10.Received attenuated live vaccine within 28 days before the first vaccination or any other vaccines (licensed or investigational) within 14 days before the first vaccination; 11.Injection of immunoglobulin and/or other blood products within 3 months before the administration of study vaccine; 12.Long-term use (continuous use >14 days) of glucocorticoids (≥10mg/day of prednisone or its equivalent dose) or other immunosuppressive agents; however, enrollment is allowed for the following conditions: inhaled or topical use of topical steroids, or short-term use (treatment course ≤14 days) of oral steroids; 13.Pregnant or breastfeeding women; 14.Planning to donate blood during the study period; 15.Suspected or known alcohol or drug dependence; 16.History of severe psychiatric disorders which may affect study participation; 17.Planning to permanently move from the local area before study completion or leave the local area for a long time during the period of study visits, so that the scheduled visits cannot be followed; 18.Those considered by the investigator as inappropriate to participate in the study.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V-01 COVID-19 Vaccine<br>Intramuscular injection into the lateral deltoid of the upper arm Two doses, one each on Day 0 and 21 (+7 days), respectively. | Biological: Recombinant SARS-CoV-2 fusion protein vaccine (V-01)<br>* Appearance: creamy white suspension Dosage form: Suspension for injection Strength: 10 μg (0.5mL) /vial Vaccination route: intramuscular injection into the lateral deltoid of the upper arm Vaccination dosage: 10 μg Immunization schedule: two doses, one each on Day 0 and 21 (+7 days), respectively. Storage condition: store at 2 8°C protected from light Expiry date: 24 months after production date<br>* Other names: V-01;|
| Placebo Comparator: Placebo control<br>Intramuscular injection into the lateral deltoid of the upper arm Two doses, one each on Day 0 and 21 (+7 days), respectively. | Other: Blank Preparation of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01)<br>* The dosage, appearance, administration method, and other aspects are consistent with that of investigational vaccine, except that no vaccine antigen is contained.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The efficacy of V-01 for the prevention of symptomatic RT-PCR-positive COVID-19 (mild or above in severity) | To evaluate the efficacy of the recombinant SARS-CoV-2 fusion protein vaccine (V-01) for the prevention of symptomatic RT-PCR-positive COVID-19 (mild or above severity) starting from at least 14 days (≥15 days) after full-course immunization (completing all vaccinations); | More than 14 days (≥15 days) after full course immunization | 
| The incidence of adverse events (AEs) of V-01 | To evaluate the incidence of adverse events (AEs) of recombinant SARS-CoV-2 fusion protein vaccine (V-01) from the first vaccination to 28 days after full-course immunization | From the first vaccination to 28 days after full-course immunization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The efficacy of V-01 for the prevention of COVID-19 of severe or above in severity | To evaluate the efficacy of the recombinant SARS-CoV-2 fusion protein vaccine (V-01) for the prevention of COVID-19 of severe or above severity starting from at least 14 days (≥15 days) after full-course immunization; | More than 14 days (≥15 days) after full-course immunization; | 
| The efficacy of V-01 for the prevention of symptomatic RT-PCR-positive COVID-19 (mild or above in severity) | To evaluate the efficacy of the recombinant SARS-CoV-2 fusion protein vaccine (V-01) for the prevention of symptomatic RT-PCR-positive COVID-19 (mild or above in severity) starting from more than 14 days after the first vaccination; | More than 14 days (≥15 days) after full-course immunization; | 
| The efficacy of V-01 for the prevention of symptomatic RT-PCR-positive COVID-19 (mild or above in severity) in different age groups | To evaluate the efficacy of the recombinant SARS-CoV-2 fusion protein vaccine (V-01) for the prevention of symptomatic RT-PCR-positive COVID-19 (mild or above in severity) starting from more than 14 days after full-course immunization in different age groups | More than 14 days (≥15 days) after full-course immunization; | 
| The morbidity of suspected but not confirmed COVID-19 (negative or not detected) | To evaluate the morbidity of suspected but not confirmed COVID-19 (negative or not detected) | More than 14 days (≥15 days) after full-course immunization; | 
| The mortality caused by COVID-19 | To evaluate the mortality caused by COVID-19 | More than 14 days (≥15 days) after full-course immunization; | 
| The hospitalization rate caused by COVID-19 | To evaluate the hospitalization rate caused by COVID-19 | More than 14 days (≥15 days) after full-course immunization; | 
| The incidence of serious adverse events (SAEs) and adverse events of special interest (AESIs) | To evaluate the incidence of serious adverse events (SAEs) and adverse events of special interest (AESIs) occurred from the first dose of recombinant SARS-CoV-2 fusion protein vaccine (V-01) to 12 months after full-course immunization | From the first dose of recombinant SARS-CoV-2 fusion protein vaccine (V-01) to 12 months after full-course immunization | 
| The seroconversion rate of serum SARS-CoV-2 RBD protein-binding antibody, geometric mean titer (GMT) and geometric mean increase (GMI) | To evaluate the seroconversion rate of serum SARS-CoV-2 RBD protein-binding antibody, geometric mean titer (GMT) and geometric mean increase (GMI) at day 28, month 3, month 6, and month 12 after full-course immunization (enzyme-linked immunosorbent assay [ELISA]); To evaluate the seroconversion rate of serum anti-SARS-CoV-2 neutralizing antibody, GMT and GMI at day 28, month 3, month 6, and month 12 after full-course immunization (live virus neutralization assay); | At day 28, month 3, month 6, and month 12 after full-course immunization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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V-01