Phase 1, safety, immunogenicity and dose finding for two strengths of 0.5 × 10^6 and 2.5 × 10^6 (TCID50) inactivated SARS-CoV-2 vaccine FAKHRAVAC (MIVAC) injected in two schedules of two doses, 2 and 3 weeks apart in healthy adults aged 18-55 years: a randomized, double blind, placebo controlled, clinical trial
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Protocol summary
Inclusion criteria: Age 18 to 55 years; Body mass index between 18 to 35; no abnormal clinical and laboratory findings; No current or previous infection with COVID-19; Use of safe methods of contraception; Signing informed consent form
Exclusion criteria: Current acute or chronic illness requiring regular medical or surgical attention; High-risk occupations exposed with Covid-19; serving in obligatory military service; Breastfeeding; Pregnancy;
Inclusion criteria: Age 18 to 55 years; BMI 18 to 35; no abnormal clinical and laboratory findings; No current or previous infection with COVID-19; Use of safe methods of contraception; Signing informed consent form
Exclusion criteria: Current acute or chronic illness requiring regular medical or surgical attention; High-risk occupations exposed with Covid-19; serving in obligatory military service; Breastfeeding; Pregnancy;
Inclusion criteria: Age 18 to 55 years; Body mass index betweenBMI 18 to 35; no abnormal clinical and laboratory findings; No current or previous infection with COVID-19; Use of safe methods of contraception; Signing informed consent form Exclusion criteria: Current acute or chronic illness requiring regular medical or surgical attention; High-risk occupations exposed with Covid-19; serving in obligatory military service; Breastfeeding; Pregnancy;
General information
FAKHRAVAC
FAKHRAVAC
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135
135
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2021-03-16, 1399/12/26
2021-03-16 00:00:00
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2021-04-13, 1400/01/24
2021-04-13 00:00:00
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2022-04-13, 1401/01/24
2022-04-13 00:00:00
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Recording of the actual start and end recruitment date
Recording of the actual start and end recruitment date
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اعلام تاریخ شروع و پایان بیمارگیری تحقق یافته
اعلام تاریخ شروع و پایان بیمارگیری تحقق یافته
Protocol summary
Study aim
Dose finding, safety and immunogenicity of Covid 19 FAKHRAVAC (MIVAC) inactivated vaccine in healthy population 18-55 years
Design
Randomized, double blind, controlled trial with factorial design on 135 volunteers. Fifteen sentinels without blinding and 120 in five groups of 24, double blind and randomized
Settings and conduct
Fakhra clinical trial center, Persian Gulf Hall, Sased Sports Complex, Shahid Fakhrizadeh Street, Sayad Shirazi Highway, Tehran, Iran
Participants/Inclusion and exclusion criteria
Inclusion criteria: Age 18 to 55 years; BMI 18 to 35; no abnormal clinical and laboratory findings; No current or previous infection with COVID-19; Use of safe methods of contraception; Signing informed consent form
Exclusion criteria: Current acute or chronic illness requiring regular medical or surgical attention; High-risk occupations exposed with Covid-19; serving in obligatory military service; Breastfeeding; Pregnancy;
Intervention groups
Group 1: vaccine strength of 0.5*10^6 (TCID50), two doses at 14-day intervals
Group 2: vaccine strength of 2.5*10^6, two doses at 14-day intervals
Group 3: placebo, two doses at 14-day intervals
Group 4: vaccine strength of 0.5*10^6, two doses at 21-day intervals
Group 5: vaccine strength of 2.5*10^6, two doses at 21-day intervals
Group 6: placebo two doses at 21-day intervals
Main outcome variables
Primary outcomes: Reactogenicity (vital signs and anaphylactic reactions 3 hours post-vaccination; Local and systemic adverse events within the first week post-vaccination; Abnormal laboratory findings one week after
Secondary outcomes: SAEs, SUSARs, MAAEs up to six months after the last dose of the vaccine; Occurrence of Covid-19 disease two weeks after the second dose of the vaccine onward; Serum IgG level for SARS-CoV-2 to N and S antigens; Neutralizing antibody activity; Cell medicated immunity and safety of cell mediated immune response
General information
Reason for update
Recording of the actual start and end recruitment date
Acronym
IRCT registration information
IRCT registration number:IRCT20210206050259N1
Registration date:2021-03-08, 1399/12/18
Registration timing:prospective
Last update:2021-10-23, 1400/08/01
Update count:4
Registration date
2021-03-08, 1399/12/18
Registrant information
Name
Ahmad Karimi Rahjerdi
Name of organization / entity
Stem Cell Technology Research Center
Country
Iran (Islamic Republic of)
Phone
+98 21 2208 2120
Email address
rahjerdi@strc.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-03-10, 1399/12/20
Expected recruitment end date
2021-04-09, 1400/01/20
Actual recruitment start date
2021-03-16, 1399/12/26
Actual recruitment end date
2021-04-13, 1400/01/24
Trial completion date
2022-04-13, 1401/01/24
Scientific title
Phase 1, safety, immunogenicity and dose finding for two strengths of 0.5 × 10^6 and 2.5 × 10^6 (TCID50) inactivated SARS-CoV-2 vaccine FAKHRAVAC (MIVAC) injected in two schedules of two doses, 2 and 3 weeks apart in healthy adults aged 18-55 years: a randomized, double blind, placebo controlled, clinical trial
Public title
trial of safety, immunogenicity and dose finding for inactivated SARS-CoV-2 vaccine FAKHRAVAC (MIVAC)
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Age 18 to 55 years
Body mass index between 18 and 35 kg per square meter
Having complete health based on clinical and laboratory criteria
No current or previous COVID-19 disease
No pregnancy
Useing safe methods of contraception
Signing the informed consent form
Having Iranian citizenship
Participants should be able to read and understand informed consent, preferably with a diploma or higher certificate
Temperatures less than or equal to 37.2 ° C sublingually measured by an electronic thermometer
Negative IgG and IgM antibody titers against COVID-19 N antigen
Negative RT-PCR -test for SARS-CoV-2
IgG ELISA negative blood test against HIV
Heart rate between 60 and 100
Systolic blood pressure (between 90 and 140 mm Hg), diastolic blood pressure (between 60 and 90 mm Hg)
Accept commitments to reduce the risk of COVID-19
Negative pregnancy test for β-hCG on the day of screening and the day of vaccination
Clinical trial participants should refrain from donating blood or plasma from the first vaccination until 3 months after the last vaccination.
Participants should not enter any other trial while in this study
Expressing a person's readiness to remain among the people monitored in the study for the entire study period until the research process is completed within 14 months
Use one of a safe method of contraception in men and women up to 3 months after the last dose of the vaccine
Exclusion criteria:
Current acute or chronic symptomatic illness that requires ongoing medical or surgical care
high-risk occupations regarding risk of COVID-19, including medical staff, occupations with close contact with many client
Serving in compulsory military service (soldiers) in the subdivisions of the Armed Forces
Breastfeeding
History of receiving any research vaccine during the 30 days prior to the day of screening
History of transfusion of any blood product or immunoglobulin within the 3 months before the screening day
History of long-term use of immunosuppressive drugs or systemic corticosteroids in the last 4 months leading up to screening day
History of allergic diseases such as angioedema or anaphylactic reactions
History of any allergy to drugs or vaccines
History of cancer or chemotherapy in the last 5 years
History of serious psychiatric illnesses
History of blood disorders (Blood Dyscrasias, coagulation, platelet deficiency or disorder, etc)
Having chronic obstructive pulmonary disease such as asthma and COPD, ischemic cardiovascular disease diagnosed and treated by a specialist.
high blood pressure that is being treated by a doctor.
diabetes that is being treated by a doctor.
History of chronic neurological diseases (including seizures and epilepsy)
Any history of drug abuse (addiction) or alcohol consumption during the last 2 years
Any grade 1 toxicity in the hematology or biochemistry test results performed at the time of screening
History of confirmed COVID-19
Acute or chronic hepatitis B and C
Receiving prophylactic drug against tuberculosis
History of syncope with injection or blood observation
having a splenectomy for any reason
Any close contact with a definitively infected person with COVID-19 for a maximum of two weeks before the day of receiving the first dose
Age
From 18 years old to 55 years old
Gender
Both
Phase
1
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Data and Safety Monitoring Board
Sample size
Target sample size:
135
Actual sample size reached:
135
Randomization (investigator's opinion)
Randomized
Randomization description
In this study, the Block Randomization method with different block sizes was used to assign each participant to the intervention groups. The rand() function of Excel software will be used to generate random sequence within each block. After determining the allocated intervention, a non-repetitive four-digit random code was assigned to each participant. Assigned codes will be delivered to the eligible participants via a software.
Blinding (investigator's opinion)
Double blinded
Blinding description
In this study, placebo will be used. Adjunct only IMP will be used as placebo. All people involved in the study will be blind to the type of IMP received except the epidemiologist responsible for unblinding. In cases of any serious adverse event or any trend in the occurrence of adverse events towards one of the groups, unblinding will occur by DSMB request. In other clinical occasions unblinding could occur by the principle investigators' approval
Placebo
Used
Assignment
Factorial
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
National Research Ethics committee
Street address
Floor 13, Block A, Ministry of Health & Medical Education Headquarters, Between Zarafashan & South Falamak, Qods Town, Tehran, Iran.
City
Tehran
Province
Tehran
Postal code
7334144696
Approval date
2021-02-28, 1399/12/10
Ethics committee reference number
IR.NREC.1399.006
Health conditions studied
1
Description of health condition studied
SARS-CoV-2
ICD-10 code
U07.1 COVI
ICD-10 code description
U07.1 COVID-19, virus identified
Primary outcomes
1
Description
Abnormal vital signs and anaphylactic reactions immediately after vaccination. Vital signs include body temperature, Respiratory rate, heart rate, systolic and diastolic blood pressure before and immediately after vaccination.
Timepoint
In the first three hours after each vaccination
Method of measurement
Temperature is measured using a digital thermometer under the tongue. Heart rate and respiratory rate will be counted by the research staff in one minute. Blood pressure will be measured by a digital sphygmomanometer while sitting.
2
Description
Local adverse events within the first week post-vaccination including pain, tenderness, erythema and redness, and swelling and stiffness
Timepoint
For the first 7 days after each vaccination
Method of measurement
Study staff will contact participants daily for seven days and complete a local adverse event form.
3
Description
Systemic adverse event within the first week post-vaccination including nausea and vomiting, diarrhea, headache, fatigue, muscle pain, and other illnesses or clinical complications
Timepoint
For the first 7 days after each vaccination and then monthly for up to six months
Method of measurement
Study staff will contact participants daily for seven days and complete a systemic adverse event form.
Up to six months after the last dose of the vaccine
Method of measurement
Complications will be assessed by telephone each month
2
Description
Occurrence of Covid-19 disease
Timepoint
Two weeks after the second dose of the vaccine
Method of measurement
PCR test
3
Description
Serum IgG level for SARS-CoV-2 N and S antigens
Timepoint
In the vaccination program 0-14: on days zero, 7, 14, 28, 42, 72 and months 3, 6, 9, 12 and in the vaccination program 21-0: on days zero, 7, 14, 21, 35, 49 and months 3, 6, 9, 12.
Method of measurement
ELISA method
4
Description
Neutralizing antibody activity
Timepoint
In the vaccination program 0-14: on days zero, 14, 28, 42 and months 3, 6, 9, 12 and in the vaccination program 21-0: on days zero, 21, 35, 49 and months 3, 6, 9, 12.
Method of measurement
SARS-CoV-2 virus neutralizing antibody titer
5
Description
Cell-mediated immunity and cell immunogenicity safety
Timepoint
In the vaccination program 0-14: on days zero, 14, 28, 42 and months 3, 6, 9, 12 and in the vaccination program 21-0: on days zero, 21, 35, 49 and months 3, 6, 9, 12.This outcome will be measured on day 0 and 2 weeks after the second injection for all volunteers and at other time points for 20% of participants.
Method of measurement
Absolute measurement of lymphocyte cell subpopulations (B, T, NK) and their ratio, measurement of T cell subpopulations (CD3 + CD4 +, CD3 + CD8 +), measurement of TNF-a and interleukins 4, 5, 2, 17, 6, 12, 17A, 17F, 21, 8 and 10. Cell proliferation using CFSE method. Measurement of intracellular gamma interferon (interleukin-4 and TNF-alpha) in antigen-exposed CD4 and CD8 cells
Intervention groups
1
Description
Intervention group 1: Two times vaccines in the deltoid muscle (IM) with a dose of 0.5*10^6 (TCID50) at 14-day intervals
Category
Prevention
2
Description
Intervention group 2: Two times vaccines in the deltoid muscle (IM) with a dose of 2.5*10^6 (TCID50) at 14-day intervals
Category
Prevention
3
Description
Control group 1: Two times placebo in the deltoid muscle (IM) at 14-day intervals
Category
Placebo
4
Description
Intervention group 3: Two times vaccines in the deltoid muscle (IM) with a dose of 0.5*10^6 (TCID50) at 21-day intervals
Category
Prevention
5
Description
Intervention group 4: Two times vaccines in the deltoid muscle (IM) with a dose of 2.5*10^6 (TCID50) at 21-day intervals
Category
Prevention
6
Description
Control group 2: Two times placebo in the deltoid muscle (IM) at 21-day intervals