Phase I Clinical Trial of a COVID-19 Vaccine in 18-60 Healthy Adults (CTCOVID-19)

A Single-center,Open-label，Dose-escalating Phase I Clinical Trial to Evaluate Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) in Healthy Adults Aged 18-60 Years Old

The 2019 novel-coronavirus (2019-nCov) is the cause of a cluster of unexplained pneumonia that started in Hubei province in China. It has manifest into a global health crisis with escalating confirmed cases and spread across many countries.

In view of the fact that there is currently no effective antiviral therapy, the prevention or treatment of diseases caused by COVID-19 can be tough for current treatment.

This study is a phase I clinical trial. The investigators intent to evaluate the safety, reactogenicity and immunogenicity of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) .

Study Overview

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

Detailed Description

This is a single-center,open-label，dose-escalating phase I clinical trial in healthy 18 to 60 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) manufactured by Beijing Institute of Biotechnology and CanSino Biologics Inc.One hundred and eight subjects will be enrolled into one of three cohorts and will receive an intramuscular (IM) injection of experimental vaccine or placebo on Days 1 in the deltoid muscle.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Hubei Provincial Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged between 18 and 60 years.
• Able to understand the content of informed consent and willing to sign the informed consent
• Able and willing to complete all the secluded study process during the whole 6 months study follow-up period.
• Negative in HIV diagnostic test.
• Negative in serum antibodies (IgG and IgM) screening of COVID-19.
• Normal in lung CT images (no imaging features of COVID-19
• Axillary temperature ≤37.0°C.
• The BMI index is 18.5-30.0.
• Negative in Nasopharyngeal swabs / sputum and anal swabs through RT-PCR
• Laboratory tests such as hematological examination and clinical biochemistry examination are in the normal range or without meaning judged by clinical doctor.
• General good health as established by medical history and physical examination.

Exclusion Criteria:

• Family history of seizure, epilepsy, brain or mental disease
• Subject allergic to any component of the investigational vaccine, or a more severe allergic reaction and history of allergies in the past.
• Woman who is pregnant, breast-feeding or positive in β-HCG (human chorionic gonadotropin) pregnancy test (urine) on day of enrollment, or become pregnant during the next 6 months
• Any acute fever disease or infections.
• History of SARS
• Major congenital defects or not well-controlled chronic illness, such as asthma, diabetes, or thyroid disease.
• Serious cardiovascular diseases, such as arrhythmia, conduction block, myocardial infarction, severe hypertension without controllable drugs, etc.
• Hereditary angioneurotic edema or acquired angioneurotic edema
• Urticaria in last one year
• No spleen or functional spleen.
• Platelet disorder or other bleeding disorder may cause injection contraindication
• Faint at the sight of needles.
• Prior administration of immunodepressant or corticosteroids, antianaphylaxis treatment, cytotoxic treatment in last 6 months.
• Prior administration of blood products in last 4 months
• Prior administration of other research medicines in last 1 month
• Prior administration of attenuated vaccine in last 1 month
• Prior administration of inactivated vaccine in last 14 days
• Current anti-tuberculosis prophylaxis or therapy
• According to the judgement of investigator,various medical, psychological, social or other conditions, those could affect the subjects to sign informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose Group; Subjects received one dose of 5E10 vp Ad5-nCoV at 18 to 60 years old	Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector); Intramuscular other name:Ad5-nCoV
Experimental: Middle-dose Group; Subjects received one dose of 1E11 vp Ad5-nCoV at 18 to 60 years old	Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector); Intramuscular other name:Ad5-nCoV
Experimental: High-dose Group; Subjects received one dose of 1.5E11vp Ad5-nCoV at 18 to 60 years old	Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector); Intramuscular other name:Ad5-nCoV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety indexes of adverse reactions	Occurrence of adverse reactions post-vaccination	0-7 days post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety indexes of adverse events	Occurrence of adverse events post-vaccination	0-28 days post-vaccination
Safety indexes of SAE	Occurrence of serious adverse events post-vaccination	0-28 days, within 6 mouths post-vaccination
Safety indexes of lab measures	Occurrence of abnormal changes of laboratory safety examinations	pre-vaccination, day 7 post-vaccination
Immunogencity indexes of GMT(ELISA)	Geometric mean titer（GMT）of S-specific antibodies against 2019 novel coronavirus tested by ELISA in serum	day14,28，month 3,6 post-vaccination
Immunogencity indexes of GMT(pseudoviral neutralization test method)	Geometric mean titer（GMT）of S-specific antibodies against 2019 novel coronavirus tested by pseudoviral neutralization test method in serum	day14,28，month 6 post-vaccination
Immunogencity indexes of seropositivity rates(ELISA)	the seropositivity rates of S-specific antibodies against 2019 novel coronavirus tested by ELISA in serum	day14,28，month 3,6 post-vaccination
Immunogencity indexes of seropositivity rates(pseudoviral neutralization test method)	the seropositivity rates of S-specific antibodies against 2019 novel coronavirus tested by pseudoviral neutralization test method in serum	day14,28，month 6 post-vaccination
Immunogencity indexes of GMI(ELISA)	Geometric mean fold increase（GMI）of S-specific antibodies against 2019 novel coronavirus tested by ELISA in serum	day14,28，month 3,6 post-vaccination
Immunogencity indexes of GMI(pseudoviral neutralization test method)	Geometric mean fold increase（GMI）of S-specific antibodies against 2019 novel coronavirus tested by pseudoviral neutralization test method in serum	day14,28，month 6 post-vaccination
Immunogencity indexes of GMC(Ad5 vector)	Geometric mean concentration（GMC）of anti-Ad5 vector neutralizing antibody responses	day、14,28，month3,6 post-vaccination
Immunogencity indexes of GMI(Ad5 vector)	Geometric mean fold increase（GMI）of anti-Ad5 vector neutralizing antibody responses	day、14,28，month3,6 post-vaccination
Immunogencity indexes of cellular immune	specific cellular immune responses	day 14, 28,month 6 post-vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consistency analysis(ELISA and pseudoviral neutralization test method)	Consistency analysis of S-specific antibodies against 2019 novel coronavirus tested by ELISA against those tested by pseudoviral neutralization test method	day,14,28, month 6 post-vaccination
Dose-response relationship（Humoral immunity）	Relationship between Geometric mean titer (GMT) of S protein-specific antibodies against 2019 novel coronavirus and vaccine dose among study groups	day14,28，month 3,6 post-vaccination
Persistence analysis of anti-S protein antibodies	Persistence analysis of anti-S protein antibodies among study groups	day14,28，month 3,6 post-vaccination
Time-dose-response relationship（Humoral immunity）	Relationship between the appearance time of S-specific antibodies against 2019 novel coronavirus and the vaccination dose.	day14,28，month 3,6 post-vaccination
Dose-response relationship（ cellular immunity）	Relationship between cellular immune levels against 2019 novel coronavirus and vaccine dose among study groups	day 14, 28,month 6 post-vaccination
Persistence analysis of cellular immuse	Persistence analysis of specific cellular immune response	day 14, 28,month 6 post-vaccination
Time-dose-response relationship（cellular immunity）	Relationship between the appearance time of cellular immunity against 2019 novel coronavirus and the vaccination dose.	day 14, 28,month 6 post-vaccination

Collaborators and Investigators

• Sponsor: CanSino Biologics Inc.
• Collaborators: Tongji Hospital; Jiangsu Province Centers for Disease Control and Prevention; Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China; Hubei Provincial Center for Disease Control and Prevention
• Investigators: Principal Investigator: Zhu Fengcai, Jiangsu Province Centers for Disease Control and Prevention; Principal Investigator: Guan Xuhua, Hubei Provincial Center for Disease Control and Prevention; Principal Investigator: Wang Wei, Tongji Hospital

Publications and helpful links

General Publications

• Zhu FC, Li YH, Guan XH, Hou LH, Wang WJ, Li JX, Wu SP, Wang BS, Wang Z, Wang L, Jia SY, Jiang HD, Wang L, Jiang T, Hu Y, Gou JB, Xu SB, Xu JJ, Wang XW, Wang W, Chen W. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet. 2020 Jun 13;395(10240):1845-1854. doi: 10.1016/S0140-6736(20)31208-3. Epub 2020 May 22.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2020
• Primary Completion (Actual): January 20, 2021
• Study Completion (Actual): February 20, 2021

Study Registration Dates

• First Submitted: March 15, 2020
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (Actual): March 18, 2020

Study Record Updates

• Last Update Posted (Actual): August 4, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Safety; Infection; vaccine; COVID-19; Immunogenicity; Ad5; Dose-escalation; novel coronavirus
• 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
• Other Study ID Numbers: JSVCT088

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: We support data sharing of the individual participant data. The individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendixes) will be shared. Individual participant data will be available beginning 3 months and ending one year following article publication. Supporting clinical documents including study protocol, statistical analysis plan (SAP), and the informed consent form (ICF) will be available immediately following publication for at least one year. Supporting clinical documents access information will be available at http://www.jshealth.com/. Researchers who provide a scientifically sound proposal will be allowed to access to the individual participant data. Proposals should be directed to jszfc@vip.sina.com or cw0226@foxmail.com.
• IPD Sharing Time Frame: Data will be available beginning 3 months and ending one year following article publication
• IPD Sharing Access Criteria: Data access requests will be reviewed by the sponsor，investigator and collaborators on the basis of scientific merit. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

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