Phase Ⅰ Clinical Trial of a Candidate COVID-19 Vaccine

Study Overview
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Brief Summary
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In this trial, a single-arm, open-label study design will be used to evaluate the safety and tolerability after vaccination with escalating doses of the investigational vaccine (Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation, RCVi) at low, medium, and high doses in healthy adults (previously primed with authorized vaccines).

Official Title
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A Single-arm, Open-label Phase I Clinical Study to Evaluate the Safety, Tolerability and Immunogenicity of Recombinant COVID-19 Vaccine (Adenovirus Vector) for Inhalation in People 21 to 65 Years Old (Previously Primed With Authorized Vaccines)

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: People aged 21 to 65 years old, with body weight ≥ 50 kg for males and ≥ 45 kg for females, body mass index (BMI) within the range of 19.0-30.0 (including the boundary value), who can provide legal identification; Subjects who agree to participate in this study voluntarily and sign an Informed Consent Form. Subject who has the ability to understand the study procedures and be able to attend all scheduled follow-up; Individuals who completed basic vaccination of licensed vaccine or further received the first booster dose vaccination 4 12 months prior to recruitment in this study（including but not limited to mRNA or non-mRNA vaccine）. Female subjects who are not pregnant or breast-feeding; Women of childbearing age who agree to use effective contraception during the study; or have been using effective contraception within 2 weeks prior to enrollment. Exclusion Criteria: Those who had fever (body temperature≥ 38.0 °C/100.4 °F), dry cough, fatigue, nasal congestion, runny nose, sore throat, myalgia, diarrhea, shortness of breath, and dyspnea in the past 14 days before vaccination; Subject whose SARS-CoV-2 nucleic acid test result is positive; Subject with a body temperature of ≥ 38.0 °C/100.4 °F (axillary temperature) on the day of enrollment; Subject who has oral ulcers, throat swelling and other oral and nasopharyngeal diseases; Subject with abnormal vital signs, physical examination and laboratory test indicators at screening that are judged by clinicians to be clinically significant; Subject who has a previous history of severe allergy to any drug, food or vaccination, such as urticaria, anaphylactic shock, allergic laryngeal edema, allergic dyspnea, skin eczema, Henoch-Schonlein purpura, thrombocytopenic purpura, local allergic necrosis reaction (Arthus reaction), etc.; Subject who has suffered from acute disease or in the acute attack stage of chronic disease within 3 days before vaccination, or has used antipyretic, analgesic and anti-allergy drugs; Subject within 6 months prior to vaccination participation in a coronavirus (MERS-CoV, SARS-CoV-2) vaccine and/or drug (small molecule) and/or antibody study; Participation in any clinical study within 3 months prior to vaccination or planned participation in other (drug or vaccine) clinical studies during the study; Subject who has received other vaccines within 1 month before vaccination; Subject who has used immunoenhancers or immunosuppressants in the past 3 months; Subject who was diagnosed with congenital or acquired immunodeficiency, or suspected to have systemic diseases that may interfere with the conduct or completion of the study, such as tuberculosis, hepatitis B, hepatitis C, human immunodeficiency virus (HIV), syphilis infection, etc.; Subject who was diagnosed with serious diseases, congenital anomalies or chronic disease that may interfere with the conduct or completion of the study (including but not limited to: allergy to vaccines, asthma and other respiratory diseases or chronic bronchitis, hypertension, hypotension, heart disease, kidney disease, diabetes mellitus (type 1 or type 2), autoimmune diseases, thalassemia, malignant tumor, atopy, existing skin diseases, etc.); Subject who has received blood or blood-related products (such as blood transfusion, use of human albumin, human immunoglobulin, etc.) within the past 6 months; Subject with a history or family history of convulsions, epilepsy, encephalopathy and psychosis; Subject with functional asplenia or splenectomy caused by any situation; Subject who has any condition that, in the opinion of the investigator, may interfere with the evaluation of the objectives of the study.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br>21 65 year old healthy subjects, received low dose of RCVi | Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation<br>* 0.2mL/dose, Inhalation using a nebulizer<br>* Other names: RCVi;|
| Experimental: Medium dose<br>21 65 year old healthy subjects, received medium dose of RCVi | Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation<br>* 0.2mL/dose, Inhalation using a nebulizer<br>* Other names: RCVi;|
| Experimental: High dose<br>21 65 year old healthy subjects, received high dose of RCVi | Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation<br>* 0.2mL/dose, Inhalation using a nebulizer<br>* Other names: RCVi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety in terms of adverse events | Number of Participants with any local and systemic Adverse Events (AEs) | within 30 minutes after vaccination | 
| Safety in terms of solicited AEs | Number of Participants with solicited AEs | within 7 days after vaccination | 
| Safety in terms of unsolicited AEs | Number of Participants with unsolicited AEs | within 28 days after vaccination | 
| Safety in terms of laboratory-based AEs | Changes in laboratory test indicators of clinical significance after vaccination as compared with those before vaccination | 4 days after vaccination | 
| Safety in terms of SAEs | Number of Participants with SAEs | within 6 months after vaccination | 
| Safety in terms of MAAEs and AESIs | Incidence of all Medical Attended Adverse Events (MAAEs) requiring medical attention and Adverse Events of Special Interest (AESIs) | within 6 months after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity in terms of Humoral immune response by ELISA | GMT of S protein specific antibody by ELISA | 15, 29 days, 3 and 6 months after vaccination | 
| Immunogencity in terms of Nab | GMT, seroconversion rate and GMFI of neutralizing antibody (NAb) response | 15, 29 days, 3 and 6 months after vaccination | 
| Immunogencity in terms of Cellular immune response | Intracellular cytokine levels (ICS) in T lymphocytes | 15 days after vaccination | 
| Immunogencity in terms of Mucosal immune response | Anti-SARS-CoV-2 S protein mucosal IgA antibodies | 15 days after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inhalation, COVID-19 Vaccine