History
# Registration date Revision Id
4 2022-02-26, 1400/12/07 231945
3 2021-12-20, 1400/09/29 209891
2 2021-10-23, 1400/08/01 202563
1 2021-06-08, 1400/03/18 185638
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  • Protocol summary

    Inclusion criteria: Age 18 to 70 years; Body mass index between 18 to 35; 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 18-70 years; BMI 18-35; No current or previous COVID-19 infection; Use of safe methods of contraception; Signing informed consent. Exclusion criteria: Current acute or chronic illness requiring regular medical or surgical attention; High-risk occupations exposed to Covid-19; serving in obligatory military service; Breastfeeding; Pregnancy.
    Primary outcomes: Reactogenicity (vital signs and anaphylactic reactions 3 hours post-vaccination; Local and systemic adverse events within the first week post-vaccination; Serum IgG level for SARS-CoV-2 to N, S1-RBD antigens up to a year. Secondary outcomes: Abnormal laboratory findings one week after vaccine injection; 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; Neutralizing antibody titres, and cell medicated immunity and safety of cell mediated immune response up to a year.
    Primary outcomes: Reactogenicity (vital signs and anaphylactic reactions 3 hours post-vaccination; Local and systemic adverse events within the first week post-vaccination; Serum IgG level for SARS-CoV-2 to N, S1-RBD antigens up to a year. Secondary outcomes: Abnormal laboratory findings one week after vaccine injection; 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 onwards; Neutralizing antibody activity; Cell medicated immunity and safety of cell-mediated immune response.
  • General information

    2021-07-23, 1400/05/01
    2021-07-06, 1400/04/15
    empty
    2022-01-16, 1400/10/26
    Recording of the actual start and end recruitment date
    Recording of the actual start and end recruitment date and increase in the number of humoral immunity test occasions
    اعلام تاریخ شروع و پایان بیمارگیری تحقق یافته
    اعلام تاریخ شروع و پایان بیمارگیری تحقق یافته و افزایش تعداد نوبت تست های هومورال
    Age 18 to 70 years
    Body mass index between 18 and 35 kg per square meter
    No current or previous COVID-19 disease
    No pregnancy
    Using safe methods of contraception
    Signing the informed consent form
    Having Iranian citizenship
    Participants should be able to read and understand informed consent, preferably having education at diploma or higher level
    Temperatures less than or equal to 37.2 ° C sublingually measured by a digital 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)
    Committing to observe requested behavioral protocol 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
    Age 18 to 70 years
    Body mass index between 18 and 35 kg per square meter
    No current or previous COVID-19 disease
    No pregnancy
    Using safe methods of contraception
    Signing the informed consent form
    Having Iranian citizenship
    Participants should be able to read and understand informed consent, preferably having an education at a diploma or higher level.
    Temperatures less than or equal to 37.2 ° C, sublingual, measured by a digital 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)
    Committing to observing the requested behavioral protocol 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 three months after the last vaccination.
    Participants should not enter any other trial while in this study
    Expressing readiness to remain in the study for the entire study period
    Use one of a safe methods of contraception in men and women up to 3 months after the last dose of the vaccine
    سن 18 تا 70 سال
    شاخص توده بدنی بین 18 تا 35 کیلوگرم بر متر مربع
    عدم ابتلا فعلی یا قبلی به بیماری کووید 19
    عدم بارداری
    استفاده از روش های مطمئن پیشگیری از بارداری
    امضای فرم رضایت نامه آگاهانه
    داشتن تابعیت ایرانی
    شرکت کنندگان توانایی مطالعه و درک رضایتنامه آگاهانه را داشته باشند، ترجیحا داشتن تحصیلات دیپلم و بالاتر
    درجه حرارت کمتر یا مساوی 37.2 درجه سانتی گراد زیر زبانی بر اساس تب سنج الکترونیک
    منفی بودن تیتر آنتی بادی IgG و IgM برعلیه آنتی ژن N کووید-19
    منفی بودن تست RT-PCR برای تشخیص کووید-19
    تست خونی منفی الایزا IgG برعلیه HIV
    تعداد ضربان قلب بین 60 تا 100
    فشار خون سیستولیک (بین 90 تا 140 میلی متر جیوه)، فشار خون دیاستولیک (بین 60 تا 90 میلی متر جیوه)
    قبول تعهدات مربوط به کاهش احتمال ابتلا به کووید 19
    تست منفی بارداری β-hCG در روز غربالگری و روز واکسیناسیون
    شرکت کنندگان در کارآزمائی بالینی باید از زمان اولین واکسیناسیون تا 3 ماه پس از آخرین واکسیناسیون از اهدای خون یا پلاسما خودداری کنند
    عدم شرکت فرد در کارآزمایی دیگر در طول مطالعه حاضر
    ابراز آمادگی فرد برای ماندن جزو افراد مورد پایش در مطالعه برای کل مدت مطالعه تا مراحل تحقیق طی 14 ماه پایان پذیرد
    استفاده از یک روش مطمئن پیشگیری از فرزند آوری در خانم ها و آقایان تا 3 ماه بعد از آخرین دوز واکسن
    سن 18 تا 70 سال
    شاخص توده بدنی بین 18 تا 35 کیلوگرم بر متر مربع
    عدم ابتلا فعلی یا قبلی به بیماری کووید 19
    عدم بارداری
    استفاده از روش های مطمئن پیشگیری از بارداری
    امضای فرم رضایت نامه آگاهانه
    داشتن تابعیت ایرانی
    شرکت کنندگان توانایی مطالعه و درک رضایتنامه آگاهانه را داشته باشند، ترجیحا داشتن تحصیلات دیپلم و بالاتر
    درجه حرارت کمتر یا مساوی 37.2 درجه سانتی گراد زیر زبانی بر اساس تب سنج الکترونیک
    منفی بودن تیتر آنتی بادی IgG و IgM برعلیه آنتی ژن N کووید-19
    منفی بودن تست RT-PCR برای تشخیص کووید-19
    تست خونی منفی الایزا IgG برعلیه HIV
    تعداد ضربان قلب بین 60 تا 100
    فشار خون سیستولیک (بین 90 تا 140 میلی متر جیوه)، فشار خون دیاستولیک (بین 60 تا 90 میلی متر جیوه)
    قبول تعهدات مربوط به کاهش احتمال ابتلا به کووید 19
    تست منفی بارداری β-hCG در روز غربالگری و روز واکسیناسیون
    شرکت کنندگان در کارآزمائی بالینی باید از زمان اولین واکسیناسیون تا 3 ماه پس از آخرین واکسیناسیون از اهدای خون یا پلاسما خودداری کنند
    عدم شرکت فرد در کارآزمایی دیگر در طول مطالعه حاضر
    ابراز آمادگی فرد برای ماندن جزو افراد مورد پایش در مطالعه برای کل مدت مطالعه
    استفاده از یک روش مطمئن پیشگیری از فرزند آوری در خانم ها و آقایان تا 3 ماه بعد از آخرین دوز واکسن
    Current acute or chronic symptomatic illness that requires ongoing medical or surgical care
    High-risk occupations regarding risk of acquiring COVID-19, including medical staff, occupations with close contacts 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
    Uncontrolled blood pressure (systolic higher than 140 and diastolic higher than 90)
    Uncontrolled diabetes (HbA1c higher than 6 or BS higher than 140) or diabetes treatment by insulin
    History of chronic neurological diseases (including seizures and epilepsy)
    Having thyroid disease or a history of thyroidectomy except controlled hypothyroidism
    Any history of drug/alcohol abuse (addiction) during the last 2 years
    Any grade 2 or higher 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 when seeing or giving blood
    Having 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
    Current acute or chronic symptomatic illness that requires ongoing medical or surgical care
    High-risk occupations regarding the risk of acquiring COVID-19, including medical staff, occupations with close contact with many clients
    Serving in compulsory military service (soldiers) in the subdivisions of the Armed Forces
    Breastfeeding
    History of receiving any research vaccine during the 30 days before the day of screening
    History of transfusion of any blood product or immunoglobulin within the three months before the screening day
    History of long-term use of immunosuppressive drugs or systemic corticosteroids in the last four 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
    Uncontrolled blood pressure (systolic higher than 140 and diastolic higher than 90)
    Uncontrolled diabetes (HbA1c higher than six or BS higher than 140) or diabetes treatment by insulin
    History of chronic neurological diseases (including seizures and epilepsy)
    Having thyroid disease or a history of thyroidectomy except for controlled hypothyroidism
    Any history of drug/alcohol abuse (addiction) during the last 2 years
    Any grade 2 or higher 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 when seeing or giving blood
    Having 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
    In this study, the Block Randomization method with block size of 4 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.
    In this study, the Block Randomization method with a block size of 4 was used to assign each participant to the intervention groups. The rand() function of Excel software will be used to generate random sequences 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 software.
    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
    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. On other clinical occasions, unblinding could occur by the principal investigators' approval
  • Primary outcomes

    #1
    Temperature is measured using a digital thermometer. 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
    Sublingual temperature is measured using a digital thermometer. Heart rate and respiratory rate will be counted by the research staff in one minute. Blood pressure will be measured using a digital sphygmomanometer in a sitting position.
    درجه حرارت با استفاده از ترمومتر دیجیتال در زیر زبان اندازه گیری می شود. تعداد ضربان قلب و تنفس در طول یک دقیقه و توسط پرسنل تحقیق شمارش خواهد شد. فشار خون توسط دستگاه فشار سنج دیجیتال در حالت نشسته اندازه گیری خواهد شد
    درجه حرارت با استفاده از ترمومتر دیجیتال در زیر زبان اندازه گیری می شود. تعداد ضربان قلب و تنفس در طول یک دقیقه و توسط پرسنل تحقیق شمارش خواهد شد. فشار خون توسط دستگاه فشار سنج دیجیتال در حالت نشسته اندازه گیری خواهد شد.
    #2
    For the first 7 days after each vaccine dose
    In the first seven days after each vaccine dose
    Study staff will contact participants daily for seven days and complete a local adverse event form
    Daily telephone contacts by the research team for seven days
    #3
    For the first 7 days after each vaccine dose and then monthly for up to six months
    In the first seven days after each vaccine dose and then monthly for up to six months.
    Study staff will contact participants daily for seven days and complete a systemic adverse event form
    Telephone contacts by the research team
    با شرکت کنندگان در طی هفت روز بعد از هر نوبت واکسیناسیون بصورت روزانه تماس گرفته خواهدشد و پرسنل مطالعه فرم رخداد ناخواسته سیستمیک را تکمیل خواهند کرد
    با شرکت کنندگان در طی هفت روز بعد از هر نوبت واکسیناسیون بصورت روزانه تماس گرفته خواهدشد و پرسنل مطالعه فرم رخداد ناخواسته سیستمیک را تکمیل خواهند کرد.
    #4
    on days zero, second injection day, two weeks after second injection and at 3, 6 months after the first vaccination.
    on days zero, second injection day, two and four weeks after second injection and at 3, 6 months after the first vaccination.
    در روزهای صفر، روز تزریق دوم، دو هفته بعد از تزریق دوم و ماه های 3، 6
    در روزهای صفر، روز تزریق دوم، دو و چهار هفته بعد از تزریق دوم و ماه های 3، 6
  • Secondary outcomes

    #1
    adverse events will be assessed monthly up to 6 months
    Monthly follow-up by the research team
    ارزیابی عوارض ماهانه به صورت غیرحضوری انجام خواهد گرفت.
    ارزیابی عوارض ماهانه توسط تیم پژوهش انجام خواهد گرفت.
    #2
    Occurrence of Covid-19 disease two weeks after the second vaccination dose confirmed by PCR
    Occurrence of COVID-19 disease
    Two weeks after the second dose of the vaccine up to 6 months
    Two weeks after the second dose of the vaccine to study end
    دو هفته بعد از دوز دوم واکسن تا 6 ماه
    دو هفته بعد از دوز دوم واکسن تا پایان مطالعه
    Clinical assessments and PCR test
    PCR test
    #3
    on days zero, second injection day, two weeks after second injection and at 3, 6 months after the first vaccination.
    on days zero, second injection day, two and four weeks after second injection and at 3, 6 months after the first vaccination.
    در روزهای صفر، روز تزریق دوم، دو هفته بعد از تزریق دوم و ماه های 3، 6
    در روزهای صفر، روز تزریق دوم، دو و چهار هفته بعد از تزریق دوم و ماه های 3، 6
    SARS-CoV-2 virus neutralizing antibody titer measured using a biosafety level III
    Conventional SARS-CoV-2 virus neutralizing antibody test using a biosafety level III
    #4
    Cell-mediated immunity and safety of cell mediated immune response
    Cell-mediated immunity and safety of the immune response
    Evaluation of T lymphocyte proliferative response against S antigen, Evaluation of IFN-ɣ and TNF-ɑ cytokines in PBMC cell soup stimulated by S antigen.
    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.
    بررسی پاسخ تکثیری لنفوسیتهای T در برابر آنتی ژن S و عصاره واکسن,• بررسی سایتو کاینهای IFN-ɣ و TNF-ɑ در سوپ سلولهای PBMC تحریک شده با آنتی ژن S و عصاره واکسن
    اندازه گیری مطلق زیرجمعیت های سلولی لنفوسیت ها (B, T, NK) و نسبت آنها، اندازه گیری زیرجمعیت سلولهای تی (CD3+CD4+, CD3+CD8+)، اندازه گیری TNF-a و اینترلوکین های 4 و 5 و 2 و 17 و 6 و 12 و 17 آ و 17 اف و 21 و 8 و 10.
    #5
    7 days after each vaccination, IL-6 will be measured at day zero as well
    Seven days after each vaccination, IL-6 will be measured at day zero as well
  • Intervention groups

    #1
    گروه کنترل: دریافت پلاسبو در برنامه (14-0): شرکت کنندگان این گروه دو نوبت پلاسبو FAKHRAVAC (MIVAC) را به صورت IM در عضله دلتوئید و به فاصله 14 روز دریافت می کنند.
    گروه کنترل: شرکت کنندگان این گروه دو نوبت پلاسبو FAKHRAVAC (MIVAC) را به صورت IM در عضله دلتوئید و به فاصله 14 روز دریافت می کنند.
  • Person responsible for general inquiries

    contact.organization_id:
    Name of organization / entity - English: Malek Ashtar University
    Name of organization / entity - Persian: دانشگاه مالک اشتر
    Full name of responsible person - English: Mohsen ForughiZadeh Moghadam
    Full name of responsible person - Persian: محسن فروغی زاده مقدم
    Position - English: Assistant professor
    Position - Persian: استادیار
    Latest degree: phd
    Area of specialty/work: 51
    Area of specialty/work title - English:
    Area of specialty/work title - Persian:
    Street address - English: Malek Ashtar University, Shabanloo St., Lavizan
    Street address - Persian: لویزان، خیابان شهید شعبان لو، دانشگاه مالک اشتر
    City - English: Tehran
    City - Persian: تهران
    Province: Tehran
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code: 1955737134
    Phone: +98 21 8008 6783
    Mobile: +98 919 754 7955
    Fax:
    Email: Foroughizadeh@modares.ac.ir
    Web page address:
    contact.organization_id:
    Name of organization / entity - English: Malek Ashtar University
    Name of organization / entity - Persian: دانشگاه مالک اشتر
    Full name of responsible person - English: Mohsen ForughiZadeh Moghadam
    Full name of responsible person - Persian: محسن فروغی زاده مقدم
    Position - English: Assistant professor
    Position - Persian: استادیار
    Latest degree: phd
    Area of specialty/work: 51
    Area of specialty/work title - English:
    Area of specialty/work title - Persian:
    Street address - English: No. 12, Zomorod 1 block, Noor 1 St., Shahid Mahalati Town
    Street address - Persian: شهرک شهید محلاتی، خ نور 1،بلوک زمرد 1،واحد 12
    City - English: Tehran
    City - Persian: تهران
    Province: Tehran
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code: 1955737134
    Phone: +98 21 8008 6783
    Mobile: +98 919 754 7955
    Fax:
    Email: Foroughizadeh@modares.ac.ir
    Web page address:

Protocol summary

Study aim
Safety and immunogenicity of Covid 19 FAKHRAVAC (MIVAC) inactivated vaccine in healthy population 18-70 years
Design
Randomized, double blind, controlled trial with parallel design on 500 volunteers in 2 groups of 250, double blind and randomized.
Settings and conduct
Fakhra clinical trial center, Persian Gulf Hall, SASAD Sports Complex, Shahid Fakhrizadeh Street, Sayad Shirazi Highway, Tehran, Iran
Participants/Inclusion and exclusion criteria
Inclusion criteria: Age 18-70 years; BMI 18-35; No current or previous COVID-19 infection; Use of safe methods of contraception; Signing informed consent. Exclusion criteria: Current acute or chronic illness requiring regular medical or surgical attention; High-risk occupations exposed to Covid-19; serving in obligatory military service; Breastfeeding; Pregnancy.
Intervention groups
Group 1: vaccine strength of 10 micro gram, two doses at 14-day intervals Group 2: Receiving two doses placebo at 14-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; Serum IgG level for SARS-CoV-2 to N, S1-RBD antigens up to a year. Secondary outcomes: Abnormal laboratory findings one week after vaccine injection; 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 onwards; 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 and increase in the number of humoral immunity test occasions
Acronym
IRCT registration information
IRCT registration number: IRCT20210206050259N2
Registration date: 2021-06-08, 1400/03/18
Registration timing: prospective

Last update: 2022-07-02, 1401/04/11
Update count: 3
Registration date
2021-06-08, 1400/03/18
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
2021-06-09, 1400/03/19
Expected recruitment end date
2021-07-06, 1400/04/15
Actual recruitment start date
2021-06-09, 1400/03/19
Actual recruitment end date
2021-07-06, 1400/04/15
Trial completion date
2022-01-16, 1400/10/26
Scientific title
Phase 2 trial of safety and immunogenicity of 10 micro gram inactivated SARS-CoV-2 vaccine (FAKHRAVAC), two doses two weeks apart in adults aged 18-70 years: a randomized, double-blind, placebo-controlled, clinical trial
Public title
Trial of safety and immunogenicity of 10 micro gram inactivated SARS-CoV-2 vaccine FAKHRAVAC (MIVAC)
Purpose
Prevention
Inclusion/Exclusion criteria
Inclusion criteria:
Age 18 to 70 years Body mass index between 18 and 35 kg per square meter No current or previous COVID-19 disease No pregnancy Using safe methods of contraception Signing the informed consent form Having Iranian citizenship Participants should be able to read and understand informed consent, preferably having an education at a diploma or higher level. Temperatures less than or equal to 37.2 ° C, sublingual, measured by a digital 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) Committing to observing the requested behavioral protocol 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 three months after the last vaccination. Participants should not enter any other trial while in this study Expressing readiness to remain in the study for the entire study period Use one of a safe methods 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 the risk of acquiring COVID-19, including medical staff, occupations with close contact with many clients Serving in compulsory military service (soldiers) in the subdivisions of the Armed Forces Breastfeeding History of receiving any research vaccine during the 30 days before the day of screening History of transfusion of any blood product or immunoglobulin within the three months before the screening day History of long-term use of immunosuppressive drugs or systemic corticosteroids in the last four 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 Uncontrolled blood pressure (systolic higher than 140 and diastolic higher than 90) Uncontrolled diabetes (HbA1c higher than six or BS higher than 140) or diabetes treatment by insulin History of chronic neurological diseases (including seizures and epilepsy) Having thyroid disease or a history of thyroidectomy except for controlled hypothyroidism Any history of drug/alcohol abuse (addiction) during the last 2 years Any grade 2 or higher 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 when seeing or giving blood Having 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 70 years old
Gender
Both
Phase
2
Groups that have been masked
  • Participant
  • Care provider
  • Investigator
  • Outcome assessor
  • Data and Safety Monitoring Board
Sample size
Target sample size: 500
Actual sample size reached: 500
Randomization (investigator's opinion)
Randomized
Randomization description
In this study, the Block Randomization method with a block size of 4 was used to assign each participant to the intervention groups. The rand() function of Excel software will be used to generate random sequences 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 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. On other clinical occasions, unblinding could occur by the principal investigators' approval
Placebo
Used
Assignment
Parallel
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
2021-06-07, 1400/03/17
Ethics committee reference number
IR.NREC.1400.003

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 vaccine dose
Method of measurement
Sublingual temperature is measured using a digital thermometer. Heart rate and respiratory rate will be counted by the research staff in one minute. Blood pressure will be measured using a digital sphygmomanometer in a sitting position.

2

Description
Local adverse events within the first week post-vaccination including pain, tenderness, erythema and redness, and swelling and stiffness
Timepoint
In the first seven days after each vaccine dose
Method of measurement
Daily telephone contacts by the research team for seven days

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
In the first seven days after each vaccine dose and then monthly for up to six months.
Method of measurement
Telephone contacts by the research team

4

Description
Serum IgG level for SARS-CoV-2 N, S1-RBD antigens
Timepoint
on days zero, second injection day, two and four weeks after second injection and at 3, 6 months after the first vaccination.
Method of measurement
ELISA method

Secondary outcomes

1

Description
Serious Adverse Event/Reaction(SAEs) , Suspected Unexpected Serious Adverse Reaction (SUSARs), Medically Attended Adverse Events (MAAEs)
Timepoint
Up to six months after the last dose of the vaccine
Method of measurement
Monthly follow-up by the research team

2

Description
Occurrence of COVID-19 disease
Timepoint
Two weeks after the second dose of the vaccine to study end
Method of measurement
PCR test

3

Description
Neutralizing antibody activity
Timepoint
on days zero, second injection day, two and four weeks after second injection and at 3, 6 months after the first vaccination.
Method of measurement
Conventional SARS-CoV-2 virus neutralizing antibody test using a biosafety level III

4

Description
Cell-mediated immunity and safety of the immune response
Timepoint
on days zero, second injection day, two weeks after second injection and at 3, 6 months after the first vaccination.
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.

5

Description
Abnormal laboratory findings including Hemoglobin, WBC, Lymphocytes cell, Neutrophils, Eosinophils, Platelets, ESR, CRP, LDH, CPK, RT-PCR for SARS-CoV-2, Sodium, Potassium, BUN , Creatinine, Alkaline phosphatase, ALT, AST, Bilirubin (total), U/A, Urine protein, Urine glucose, Urine RBC, IL-6
Timepoint
Seven days after each vaccination, IL-6 will be measured at day zero as well
Method of measurement
Each test will be performed using the appropriate kit

Intervention groups

1

Description
Intervention group: Two doses of 10 micro gram vaccine injected in the deltoid muscle (IM) at 14 days interval
Category
Prevention

2

Description
Control group:Two doses of placebo injected in the deltoid muscle (IM) at 14 days interval
Category
Placebo

Recruitment centers

1

Recruitment center
Name of recruitment center
Fakhra clinical trial center
Full name of responsible person
Mohsen Forughizadeh Moghadam
Street address
Fakhra clinical trial center, Persian Gulf Hall, SASAD Sports Complex, Shahid Fakhrizadeh Street, Sayad Shirazi Highway, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1986936911
Phone
+98 21 2610 1694
Email
Foroughizadeh@modares.ac.ir
Web page address
http://www.fakhravac.ir

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Organization of Defensive Innovation and Research
Full name of responsible person
Ahmad Karimi Rahjerdi
Street address
NO.9, Unit 3, Mirsharifi, Valiasr St.
City
Tehran
Province
Tehran
Postal code
1986936911
Phone
+98 21 2265 8405
Fax
+98 21 2265 8404
Email
Rahjerdi@strc.ac.ir
Web page address
http://miladpharmaceuticsco.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
No
Title of funding source
Organization of Defensive Innovation and Research
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other

Person responsible for general inquiries

Contact
Name of organization / entity
Malek Ashtar University
Full name of responsible person
Mohsen ForughiZadeh Moghadam
Position
Assistant professor
Latest degree
Ph.D.
Other areas of specialty/work
Medical Genetics
Street address
No. 12, Zomorod 1 block, Noor 1 St., Shahid Mahalati Town
City
Tehran
Province
Tehran
Postal code
1955737134
Phone
+98 21 8008 6783
Email
Foroughizadeh@modares.ac.ir

Person responsible for scientific inquiries

Contact
Name of organization / entity
Artesh University of Medical Sciences
Full name of responsible person
Ramin Hamidi Farahani
Position
Associate professor
Latest degree
Specialist
Other areas of specialty/work
Infectious diseases
Street address
NO.9, Unit 3, Mirsharifi, Valiasr St.
City
Tehran
Province
Tehran
Postal code
1986936911
Phone
+98 21 8833 7912
Email
Rgsramin@yahoo.com

Person responsible for updating data

Contact
Name of organization / entity
Milad Daro Noor Pharmaceutical Co.
Full name of responsible person
Kosar Naderi
Position
Assistant Professor
Latest degree
Ph.D.
Other areas of specialty/work
Biology
Street address
NO.9, Unit 3, Mirsharifi, Valiasr St.
City
Tehran
Province
Tehran
Postal code
1986936911
Phone
+98 21 2265 8405
Email
k.naderi@strc.ac.ir

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Yes - There is a plan to make this available
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Yes - There is a plan to make this available
Data Dictionary
Not applicable
Title and more details about the data/document
Deidentified IPD on study outcomes could be shared.
When the data will become available and for how long
After completion of the study and publication of the results, data could be shared for 2 years
To whom data/document is available
Data is available only to members of academic institutions within joint projects with MILAD Daru Nour Co.
Under which criteria data/document could be used
Proposal should be presented to MILAD Daru Nour Co and its necessity and scientific validity should be approved by the company
From where data/document is obtainable
You can contact Ms Kousar Naderi at k.naderi@strc.ac.ir
What processes are involved for a request to access data/document
Request for data will be made available within the approved joint projects
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