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

• ClinicalTrials.gov Identifier: NCT04313127
• Recruitment Status: Completed
• First Posted: March 18, 2020
• Last Update Posted: August 4, 2021
• Sponsor: CanSino Biologics Inc.
• Collaborators: Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China; Jiangsu Province Centers for Disease Control and Prevention; Hubei Provincial Center for Disease Control and Prevention; Tongji Hospital
• Information provided by (Responsible Party): CanSino Biologics Inc.

Tracking Information

• First Submitted Date: March 15, 2020
• First Posted Date: March 18, 2020
• Last Update Posted Date: August 4, 2021
• Actual Study Start Date: March 16, 2020
• Actual Primary Completion Date: January 20, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 17, 2020)

Safety indexes of adverse reactions [ Time Frame: 0-7 days post-vaccination ]

Occurrence of adverse reactions post-vaccination

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 17, 2020)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: March 17, 2020)

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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Phase I Clinical Trial of a COVID-19 Vaccine in 18-60 Healthy Adults
• Official Title: 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

Brief Summary

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) .

• 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
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: COVID-19

Intervention

Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)

Intramuscular other name:Ad5-nCoV

Study Arms

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

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 17, 2020): 108
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: February 20, 2021
• Actual Primary Completion Date: January 20, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04313127
• Other Study ID Numbers: JSVCT088
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Data will be available beginning 3 months and ending one year following article publication
• 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.
• URL: http://www.jshealth.com/

• Current Responsible Party: CanSino Biologics Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: CanSino Biologics Inc.
• Original Study Sponsor: Same as current

Collaborators

• Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China
• Jiangsu Province Centers for Disease Control and Prevention
• Hubei Provincial Center for Disease Control and Prevention
• Tongji Hospital

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

• PRS Account: CanSino Biologics Inc.
• Verification Date: May 2020