Phase I/II Clinical Trial of Recombinant Novel Coronavirus (COVID-19) Vaccine (Adenovirus Type 5 Vector) for Inhalation

Study Overview
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Brief Summary
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This study is a randomized, double-blind, placebo-controlled I/II clinical trial, in order to evaluate the safety and immunogenicity of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation in adults 18 years of Age and Older.

Official Title
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A Randomized, Double-blind, Placebo-Controlled Phase I/II Clinical Trial to Evaluate the Safety and Immunogenicity of Ad5-nCoV for Inhalation in Adults 18 Years of Age and Older

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation
* Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)
* Biological: Placebo for Inhalation
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults 18 years of age and above at the time of enrollment; Able to provide consent to participate in and having signed an Informed Consent Form (ICF); Able and willing to complete all the scheduled study procedures during the whole study follow-up period; HIV negative; No nasal or oral diseases, such as acute rhinitis (sinusitis), allergic rhinitis, oral ulcers, sore throat, etc; IgG ang IgM negative for Covid-19; Axillary temperature ≤37.0℃; No contact history of Covid-19. Exclusion Criteria: Serious cardiovascular diseases, such as arrhythmia, conduction block, myocardial infarction, severe hypertension and uncontrollable medications (on-site measurement: systolic blood pressure ≥160mmHg, diastolic blood pressure ≥100mmHg), etc; Abnormal laboratory test indicators which investigator decide to be clinically significant; (Only Phase I volunteers) Respiratory rate ≥17 per minute; Abnormal lung function such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, etc; Prior Covid-19 vaccinations; Symptoms of upper respiratory track infections; Medical or family history of convulsions, epilepsy, encephalopathy, and psychosis disorders; History of allergies to any ingredient of Ad5-nCoV, history of serious allergic reactions to any vaccine, history of allergies and immune diseases; Acute febrile diseases and infectious diseases; Medical history of SARS (SARS-CoV-1); Severe chronic diseases or with advanced stage conditions which cannot be controlled smoothly, such as diabetes, thyroid disease, etc; Congenital or acquired angioedema/neurological edema; Urticaria history within 1 year before receiving the study vaccine; Asplenia or functional asplenia; Thrombocytopenia or other coagulation disorders (may cause contraindications for intramuscular injection); Trypanophobia in intramuscular injection groups; History of receiving immunosuppressant therapy (continuous oral or instillation for more than 14 days), anti-allergic therapy, cytotoxic therapy, nebulized corticosteroid therapy in the past 6 months; Prior administration of blood products in last 4 months; Other vaccination(s) or investigational drugs within 1 month before study onset, or planned use during the study period; Prior administration of live attenuated vaccine within 1 month before study onset; Prior administration of subunit or inactivated vaccine within 14 days before study onset; Current anti-tuberculosis therapy; Women who are pregnant or lactating, positive urine pregnancy test or plan to become pregnant during the whole study; Any condition that in the opinion of the investigators may interfere with the participants' compliance or evaluation of study objectives or informed consent (i.e. medical, psychological, social or other conditions, etc.) Exclusion criteria for the phase II portion of the study will be detailed in an amended synopsis/study protocol.

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: A1a Phase I low 2 doses<br>Ad5-nCoV containing 0.5E10 vp, 2 doses 56 days apart, Aerogen Solo | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation<br>* Aerogen Solo<br>|
| Placebo Comparator: A1b Phase I placebo low 2 doses<br>Placebo containing 0 vp, 2 doses 56 days apart, Aerogen Solo | Biological: Placebo for Inhalation<br>* Aerogen Solo<br>|
| Experimental: A2a Phase I medium 2 doses<br>Ad5-nCoV containing 1E10 vp, 2 doses 56 days apart, Aerogen Solo | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation<br>* Aerogen Solo<br>|
| Placebo Comparator: A2b Phase I placebo medium 2 doses<br>Placebo containing 0 vp, 2 doses 56 days apart, Aerogen Solo | Biological: Placebo for Inhalation<br>* Aerogen Solo<br>|
| Experimental: A3a Phase I high 2 doses<br>Ad5-nCoV containing 2E10 vp, 2 doses 56 days apart, Aerogen Solo | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation<br>* Aerogen Solo<br>|
| Placebo Comparator: A3b Phase I placebo high 2 doses<br>Placebo containing 0 vp, 2 doses 56 days apart, Aerogen Solo | Biological: Placebo for Inhalation<br>* Aerogen Solo<br>|
| Experimental: A4a Phase I combine 2 doses<br>1 dose Intramuscular Injection, Ad5-nCoV containing 5E10 vp, 1 dose Aerogen Solo, Ad5-nCoV containing 2E10 vp, 56 days apart | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation<br>* Aerogen Solo<br>Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)<br>* Intramuscular administration<br>|
| Placebo Comparator: A4b Phase I placebo combine 2 doses<br>6 subjects, Placebo containing 0 vp, 1 dose Intramuscular Injection, 1 dose Aerogen Solo, 56 days apart | Biological: Placebo for Inhalation<br>* Aerogen Solo<br>Biological: Placebo<br>* Intramuscular administration<br>|
| Experimental: A5a Phase I single dose<br>Ad5-nCoV containing 1E10 vp, 1 dose Aerogen Solo | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation<br>* Aerogen Solo<br>|
| Placebo Comparator: A5b Phase I placebo single dose<br>6 subjects, Placebo containing 0 vp, 1 dose Aerogen Solo | Biological: Placebo for Inhalation<br>* Aerogen Solo<br>|
| Experimental: B1a Phase II low 2 doses<br>Ad5-nCoV containing 0.5E10 vp, 2 doses 56 days apart, Aerogen Solo | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation<br>* Aerogen Solo<br>|
| Placebo Comparator: B1b Phase II placebo low 2 doses (18-59)<br>Placebo containing 0 vp, 2 doses 56 days apart, Aerogen Solo | Biological: Placebo for Inhalation<br>* Aerogen Solo<br>|
| Experimental: B2a Phase II medium 2 doses<br>Ad5-nCoV containing 1E10 vp, 2 doses 56 days apart, Aerogen Solo | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation<br>* Aerogen Solo<br>|
| Placebo Comparator: B2b Phase II placebo medium 2 doses<br>Placebo containing 0 vp, 2 doses 56 days apart, Aerogen Solo | Biological: Placebo for Inhalation<br>* Aerogen Solo<br>|
| Experimental: B3a Phase II high 2 doses<br>Ad5-nCoV containing 2E10 vp, 2 doses 56 days apart, Aerogen Solo | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation<br>* Aerogen Solo<br>|
| Placebo Comparator: B3b Phase II placebo high 2 doses<br>Placebo containing 0 vp, 2 doses 56 days apart, Aerogen Solo | Biological: Placebo for Inhalation<br>* Aerogen Solo<br>|
| Experimental: B4a Phase II combine 2 doses<br>1 dose Intramuscular Injection, Ad5-nCoV containing 5E10 vp, 1 dose Aerogen Solo, Ad5-nCoV containing 2E10 vp, 56 days apart | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation<br>* Aerogen Solo<br>Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)<br>* Intramuscular administration<br>|
| Placebo Comparator: B4b Phase II placebo combine 2 doses<br>Placebo containing 0 vp, 1 dose Intramuscular Injection, 1 dose Aerogen Solo, 56 days apart | Biological: Placebo for Inhalation<br>* Aerogen Solo<br>Biological: Placebo<br>* Intramuscular administration<br>|
| Experimental: B5a Phase II intramuscular single dose<br>Ad5-nCoV containing 5E10 vp, 1 dose Intramuscular Injection | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)<br>* Intramuscular administration<br>|
| Placebo Comparator: B5b Phase II placebo intramuscular single dose<br>placebo containing 0 vp, 1 dose Intramuscular Injection | Biological: Placebo<br>* Intramuscular administration<br>|
| Experimental: B6a Phase II Aerogen Solo single dose<br>Ad5-nCoV containing 1E10 vp, 1 dose Aerogen Solo | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation<br>* Aerogen Solo<br>|
| Placebo Comparator: B6b Phase II placebo Aerogen Solo single dose<br>placebo containing 0 vp, 1 dose Aerogen Solo | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)<br>* Intramuscular administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Reactions (AR) | The occurrence of Adverse Reactions (AR) in all groups | 0-14 days after each vaccination | 
| Incidence of Serious Adverse Events (SAE) | The occurrence of Serious Adverse Events (SAE) in all groups | Within the first and final vaccination up until 12 months after the final vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events/Reactions (AE/AR) | The occurence of Adverse Events/Reactions (AE/AR) in all groups | Within 0-7 days after each vaccination | 
| Incidence of Adverse Events/Reactions (AE/AR) | The occurence of Adverse Events/Reactions (AE/AR) in all groups | Within 0-28 days after each vaccination | 
| Changes in laboratory test indicators | Changes in laboratory test indicators (including white blood cell count, lymphocyte count, etc), and respiratory rate in all groups | 4 days after each vaccination | 
| GMT of Covid-19 S protein RBD specific antibody | GMT of S protein RBD specific antibody by ELISA | Before the first dose, 28 days after first dose, before the second dose, 14 days after the second dose | 
| Seroconversion rate of Covid-19 S protein RBD specific antibody | Seroconversion rate of S protein RBD specific antibody by ELISA | Before the first dose, 28 days after first dose, before the second dose, 14 days after the second dose | 
| GMI of Covid-19 S protein RBD specific antibody | GMI of S protein RBD specific antibody by ELISA | Before the first dose, 28 days after first dose, before the second dose, 14 days after the second dose | 
| GMT of SARS-CoV-2 neutralizing antibody | GMT of SARS-CoV-2 neutralizing antibody against pseudovirus | Before the first dose, 28 days after the first dose, before the second dose, 14 days after the second dose | 
| Seroconversion rate of SARS-CoV-2 neutralizing antibody | Seroconversion rate of SARS-CoV-2 neutralizing antibody against pseudovirus | Before the first dose, 28 days after the first dose, before the second dose, 14 days after the second dose | 
| GMI of SARS-CoV-2 neutralizing antibody | GMI of SARS-CoV-2 neutralizing antibody against pseudovirus | Before the first dose, 28 days after the first dose, before the second dose, 14 days after the second dose | 
| GMT of SARS-CoV-2 neutralizing antibody |  | 28 days after the final vaccination | 
| Seroconversion rate of SARS-CoV-2 neutralizing antibody |  | 28 days after the final vaccination | 
| Cellular immune response | The positive rate of IFN-γ stimulated by S protein ELISpot | Before the first dose, 14 days after the first dose | 
| Cellular immune response | The positive rate of TNF-α stimulated by S protein ELISpot | Before the first dose, 14 days after the first dose | 
| Cellular immune response | The positive rate of IL-5 stimulated by S protein ELISpot | Before the first dose, 14 days after the first dose | 
| Cellular immune response | The positive rate of IL-4 stimulated by S protein ELISpot | Before the first dose, 14 days after the first dose | 
| Cellular immune response | The positive rate of IL-13 stimulated by S protein ELISpot | Before the first dose, 14 days after the first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Vaccine, Ad5, Safety, Immunogenicity, SARS-CoV-2, Adenovirus Vector, Aerogen Solo