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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: Placebo; Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector); Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation; Biological: Placebo for Inhalation

• Study Type: Interventional
• Enrollment (Actual): 840
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Provincal Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

22

Arms and Interventions

Participant Group / 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); Intramuscular administration; Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation; Aerogen Solo
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; Intramuscular administration; Biological: Placebo for Inhalation; Aerogen Solo
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); Intramuscular administration; Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) for Inhalation; Aerogen Solo
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; Intramuscular administration; Biological: Placebo for Inhalation; Aerogen Solo
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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CanSino Biologics Inc.
• Collaborators: Jiangsu Province Centers for Disease Control and Prevention; Beijing Institute of Biotechnology

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 21, 2021
• Primary Completion (ACTUAL): July 8, 2022
• Study Completion (ACTUAL): August 9, 2022

Study Registration Dates

• First Submitted: April 8, 2021
• First Submitted That Met QC Criteria: April 8, 2021
• First Posted (ACTUAL): April 12, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Safety; Vaccine; COVID-19; Immunogenicity; Ad5; Adenovirus Vector; Aerogen Solo
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: JSVCT092

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No