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

Sponsor

CanSino Biologics Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04840992

Collaborator

Beijing Institute of Biotechnology (Other), Jiangsu Province Centers for Disease Control and Prevention (Other)

840

Enrollment

Location

Arms

14.8

Anticipated Duration (Months)

56.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	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	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

840 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Apr 20, 2021

Anticipated Primary Completion Date :

Apr 15, 2022

Anticipated Study Completion Date :

Jul 15, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Incidence of Adverse Reactions (AR) [0-14 days after each vaccination]
The occurrence of Adverse Reactions (AR) in all groups
Incidence of Serious Adverse Events (SAE) [Within the first and final vaccination up until 12 months after the final vaccination]
The occurrence of Serious Adverse Events (SAE) in all groups

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.