A Clinical Trial of a Recombinant Adenovirus 5 Vectored COVID-19 Vaccine (Ad5-nCoV) With Two Doses in Healthy Adults

• ClinicalTrials.gov Identifier: NCT04552366
• Recruitment Status: Active, not recruiting
• First Posted: September 17, 2020
• Last Update Posted: December 7, 2020
• Sponsor: Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China
• Collaborator: Zhongnan Hospital
• Information provided by (Responsible Party): Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China

Tracking Information

• First Submitted Date: September 15, 2020
• First Posted Date: September 17, 2020
• Last Update Posted Date: December 7, 2020
• Actual Study Start Date: September 29, 2020
• Estimated Primary Completion Date: December 31, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 16, 2020)

• Incidence of the AE in all groups [ Time Frame: 0-7 days after each vaccination ]
  The occurrence of AE in all groups within 0-7 days after each vaccination;
• Seroconversion rate of the IgG antibody against SARS-CoV-2 [ Time Frame: Day 28 after last vaccination ]
  Seroconversion rate the IgG antibody against SARS-CoV-2 measured on Day 28 after last vaccination
• Geomean titers of the IgG antibody against SARS-CoV-2 [ Time Frame: Day 28 after last vaccination ]
  Geomean titers of the IgG antibody against SARS-CoV-2 measured on Day 28 after last vaccination
• Seroconversion rate of the neutralizing antibody against SARS-CoV-2 [ Time Frame: Day 28 after last vaccination ]
  Seroconversion rate of the neutralizing antibody against SARS-CoV-2 measured on Day 28 after last vaccination
• Geomean titers of the neutralizing antibody against SARS-CoV-2 [ Time Frame: Day 28 after last vaccination ]
  Geomean titers of the neutralizing antibody against SARS-CoV-2 measured on Day 28 after last vaccination

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 16, 2020)

• Incidence of the AE in all groups [ Time Frame: 0-30 minutes, 0-28 days after each vaccination ]
  The occurrence of AE in all groups within 0-30 minutes and 0-28 days after each vaccination.
• Incidence of Serious adverse events (SAE) in all groups [ Time Frame: 6 months after the final vaccination ]
  The occurrence of Serious adverse events (SAE) in all groups within 6 months after the final vaccination.
• Geomean titers of the IgG antibody against SARS-CoV-2 [ Time Frame: Day 0, 14, 28 and 56 after first vaccination and Day 14 and Day168 after last vaccination. ]
  Geomean titers of the IgG antibody against SARS-CoV-2 measured on Day 0, 14, 28 and 56 after first vaccination and on Day 14 and Day168 after last vaccination.
• Seroconversion rate of the IgG antibody against SARS-CoV-2 [ Time Frame: Day 0, 14, 28 and 56 after first vaccination and Day 14 and Day168 after last vaccination. ]
  Seroconversion rate of the IgG antibody against SARS-CoV-2 measured on Day 0, 14, 28 and 56 after first vaccination and on Day 14 and Day168 after last vaccination.
• Geomean titers of the neutralizing antibody against SARS-CoV-2 [ Time Frame: Day 0, 14, 28 and 56 after first vaccination and Day 14 and Day168 after last vaccination. ]
  Geomean titers of the neutralizing antibody against SARS-CoV-2 measured on Day 0, 14, 28 and 56 after first vaccination and on Day 14 and Day168 after last vaccination.
• Seroconversion rate of the neutralizing antibody against SARS-CoV-2 [ Time Frame: Day 0, 14, 28 and 56 after first vaccination and on Day 14 and Day168 after last vaccination. ]
  Seroconversion rate of the neutralizing antibody against SARS-CoV-2 measured on Day 0, Day14, Day 28 or Day 56 after first vaccination and on day 14, day 28 and day168 after last vaccination.
• Cellular immune response by ELISpot [ Time Frame: Day 0 and Day 14 after each vaccination ]
  The positive rate of IFN-γ stimulated by S protein overlapping peptide library detected by ELISpot on Day 0 and Day 14 after each vaccination
• Geomean titers of neutralizing antibody response to Ad5-vector [ Time Frame: Day 0, 14 and 28 after each vaccination. ]
  Geomean titers of neutralizing antibody response to Ad5-vector on Day 0, 14 and 28 after each vaccination.
• Cellular immune response by ICS [ Time Frame: Day 0 and Day 14 after each vaccination ]
  The positive rate of the specific cytokines expressed by CD4+ and CD8+ T lymphocytes stimulated by S protein overlapping peptide library detected by intracellular cytokine staining on Day 0 and Day 14 after each vaccination
• Geomean titers of the IgA antibody against SARS-CoV-2 [ Time Frame: Day 0, 14 and 28 after each vaccination ]
  Geomean titers of the IgA antibody against SARS-CoV-2 on Day 0, 14 and 28 after each vaccination.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Clinical Trial of a Recombinant Adenovirus 5 Vectored COVID-19 Vaccine (Ad5-nCoV) With Two Doses in Healthy Adults
• Official Title: A Clinical Trial to Evaluate the Safety and Immunogenicity of a Recombinant Adenovirus 5 Vectored COVID-19 Vaccine (Ad5-nCoV) With Two Doses in Healthy Adults Aged 18 Years and Older
• Brief Summary: This is a clinical trial to evaluate the safety and immunogenicity of a recombinant adenovirus 5 vectored COVID-19 vaccine (Ad5-nCoV) with two doses and with different adminstration routes in healthy adults aged 18 years and older.
• Detailed Description: A total of 168 healthy adult volunteers will be vaccinated in this clinical trial according to open, partly randomized design from the healthy adults aged 18 years and older. The safety and immunogenicity of intramuscular vaccination and mucosal vaccination of two doses of Ad5-nCoV in different administration schedules will be evaluated.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: COVID-19

Intervention

Biological: Ad5-nCoV

Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)

Study Arms

• Experimental: Group A: Intramuscular administration
  24 subjects. 5E10 VP of Ad5-nCoV on Day 0 and on Day 56.
  Intervention: Biological: Ad5-nCoV
• Experimental: Group B: Mixed administration
  24 subjects. An intramuscular administration of 5E10 VP of Ad5-nCoV on day 0 and a mucosal administration of 2E10 VP on Day 28.
  Intervention: Biological: Ad5-nCoV
• Experimental: Group C: Mucosal administration, high dose
  24 subjects. A mucosal administration of 2E10 VP of Ad5-nCoV on Day 0 and Day 28.
  Intervention: Biological: Ad5-nCoV
• Experimental: Group D: Mucosal administration, low dose
  24 subjects. A mucosal administration of 1E10 VP of Ad5-nCoV on day 0 and Day 28.
  Intervention: Biological: Ad5-nCoV
• Active Comparator: Group E: Intramuscular administration, one dose
  24 subjects. An intramuscular administration of 5E10 VP of Ad5-nCoV on day 0.
  Intervention: Biological: Ad5-nCoV
• Experimental: Group F: Intramuscular administration, two doses
  24 subjects. Two intramuscular administrations of 5E10 VP of Ad5-nCoV at left and right arms on day 0.
  Intervention: Biological: Ad5-nCoV

• Publications *: Wu S, Huang J, Zhang Z, Wu J, Zhang J, Hu H, Zhu T, Zhang J, Luo L, Fan P, Wang B, Chen C, Chen Y, Song X, Wang Y, Si W, Sun T, Wang X, Hou L, Chen W. Safety, tolerability, and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults: preliminary report of an open-label and randomised phase 1 clinical trial. Lancet Infect Dis. 2021 Dec;21(12):1654-1664. doi: 10.1016/S1473-3099(21)00396-0. Epub 2021 Jul 26.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 3, 2020): 149
• Original Estimated Enrollment (submitted: September 16, 2020): 168
• Estimated Study Completion Date: June 30, 2021
• Estimated Primary Completion Date: December 31, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Aged 18 years and older;
• 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 (about 6-8 months, depending on group);
• Negative result of HIV screening;
• Axillary temperature ≤37.0°C.
• Negative IgG and IgM antibodies against COVID-19;
• Good general health status, as determined by history and physical examination.

Exclusion Criteria for the first vaccination:

• Hematological examination is abnormal, or clinically significant as assessed by the study investigator (including white blood cell count, lymphocyte count, neutrophil count, eosinophil count, platelet, hemoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, blood glucose and creatinine);
• With oral ulcers, throat swelling and other oral diseases.
• With symptoms of upper respiratory tract infection.
• Personal history of seizure disorder, encephalopathy or psychosis;
• Allergic history to any vaccine, or allergic to any ingredient of the Ad5-nCoV;
• Any acute febrile disease or active infectious disease on the day of vaccination;
• History of SARS or COVID-19;
• History of COVID-19 candidate vaccine administration;
• History of chronic obstructive pulmonary disease (COPD).
• Serious cardiovascular diseases, such as arrhythmia, conduction block, myocardial infarction, severe hypertension not controlled with medication;
• Serious chronic disease or in the advanced stage that cannot be controlled well， such as asthma, diabetes and thyroid disease, etc.;
• Congenital or acquired angioedema;
• Suffered from urticaria within 1 year before receiving the trial vaccine.
• Asplenia or functional asplenia;
• Platelet disorder or other bleeding disorder that may cause intramuscular injection contraindication;
• Faint with needles in intramuscular administration group;
• Immunosuppressive medication, anti-allergic, cytotoxic therapy, inhaled corticosteroids (excluding surface corticosteroid therapy for acute non-complicated dermatitis) in the last 6 months;
• Prior administration of blood products in last 4 months;
• Other vaccination(s) or investigational drugs within 1 month before study onset;
• 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;
• Woman is pregnant or lactating, positive urine pregnancy test or plan to become pregnant during the next 8 months;
• 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 second vaccination:

• Severe allergic reaction after the first dose of vaccination;
• Severe adverse reactions causally related to the first vaccination;
• For those newly discovered or newly occured after the first vaccination that does not meet the first-dose selection criteria or meets the first-dose exclusion criteria, the investigator will determine whether to continue participating in the study;
• Other reasons for exclusion as deemed by the investigator.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older 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: NCT04552366
• Other Study ID Numbers: AMMS85-2004
• 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: No

• Responsible Party: Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China
• Study Sponsor: Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China
• Collaborators: Zhongnan Hospital
• Investigators: Not Provided
• PRS Account: Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China
• Verification Date: September 2020