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IRCT20210303050558N1 IRCT 2021-04-24 Pasture Institute of Iran Efficacy, safety and immunogenicity of Soberana 02 vaccine (product of Finlay Institute): a double-blind, randomized, placebo-controlled phase III clinical trial Efficacy, safety, and immunogenicity of Soberana recombinant vaccine (product of Finlay Institute) based on RBD protein subunit of Sars-Cov-2 in a 2-dose regimen with and without a booster dose: a double-blind, randomized, placebo-controlled phase III clinical trial in the Iranian population of 18-80 years 2021-04-25 anticipated 24000 Complete https://irct.ir/trial/54833 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Used, Assignment: Parallel, Purpose: Prevention, Randomization description: The random chain will be defined in the system before the start of the study and the list of randomized treatment groups and the corresponding codes will be delivered to the Food and Drug Administration. Random codes and the type of intervention will be assigned to the candidates based on this list, the details of which are given in the following sections. The random chain in this study will be based on the stratified block randomization method. Stratified randomization will be based on studied cities and the randomization unit is individual participants. Random blocks are a common method for constructing and allocating interventions in clinical trials in which the sample size is divided into a number of blocks of a certain size and in each block the ratio of intervention and control groups in the study is observed. Using this method, it is possible to ensure that the ratio of the intervention group to the control is observed at any time during the study. In the present study, the sample size of 24,000 people in 8 study centres (3000 people in each centre) has been determined. Each centre also has 500 codes in excess of the study size to meet the extraordinary needs of the study (for example, the decision to increase the sample size in one of the centres). The size of the blocks is 25. Therefore, for each centre, 3500 codes in 140 random blocks will be considered, in each of which there are 20 intervention codes and 5 control codes. Each intervention or control code has a unique block ID in the form of a UUID, a 1-digit code for the study centre, a block code from 1 to 140 for labeling vial-holding blocks, and a volunteer code. The volunteer code consists of 5 digits, the first digit of which is the code of the study centre and 4 digits after 1 to 3000 and is therefore unique in the study. Random chain construction is done through a program written specifically for this study. Random chain construction will be performed through a randomization program using the Python 3.8.2 programming language, which was written specifically for this study. In this program, first the total sample size, number of centers, block size, number and ratio of interventions as well as the intervention label are defined. The program then calculates the required number of blocks for each center based on its sample size and block size and creates random chains for each block. In summary, in this method, first a list of intervention and control codes in a block will be made by observing the ratio of the groups. The ordering of the indices is done using a random process in which one of the indices is selected at each stage using a uniform distribution, added in the final order and removed from the unselected indices. This process is repeated for each block, Blinding description: The unique codes of the volunteers are delivered to the preparation group and a label with the volunteer code is inserted on each vial. None of the people working in the preparation department will be in contact with those are involved in the site. Therefore, at the time of delivery of the vial block to the centres, the study colleagues will not be able to distinguish between the drug vial and the placebo. The suspensions in the vaccine and placebo vials are milky white and are similar in color and clarity. Moreover, vaccine and placebo vials are offered in similar appearance, they are inseparable, and packaging and are placed in boxes of 25. Each box will contain the block number and serial numbers of the vaccine/placebo inside. According to this process, participants, vaccinators, researchers, and outcome assessors will be blind. Vaccinators check the unique code information assigned to the candidate with the code on the vaccine/placebo vial before injection. During the study, all consumed vials will be archived and maintained. 3 Coronavirus Disease (COVID-19). Intervention 1: Intervention group in the first cohort: In 6 cities (Isfahan, Babol, Bandar Abbas, Sari, Kerman and Hamedan) 80% of people (14,400 people) receive the intervention (vaccine) after random allocation. Intervention is included intramuscular injection of vaccine candidates with conjugation of 25 μg RBD to tetanus toxin in a 2-dose program (days 0 and 28). This vaccine is made by the Finlay Institute of Vaccines. Intervention 2: Control group in the first cohort: In 6 cities (Isfahan, Babol, Bandar Abbas, Sari, Kerman and Hamedan) 20% of people (3600 people) receive a placebo after random allocation. The intervention involves an intramuscular injection of a dose of aluminum hydroxide on days 0 and 28. This placebo is made by the Finlay Institute of Vaccines. Intervention 3: Intervention group in the second cohort: In two cities (Zanjan and Yazd) 80% of people (4800 people) receive the intervention (vaccine) after random allocation. The intervention includes: a 2-dose program + a booster dose (days 0, 28, 56). The booster dose of the candidate vaccine is Sobrana Plus (50 micrograms d-RBD +, IM 0.5 ml). This vaccine is made by the Finlay Institute of Vaccines. Intervention 4: Control group in the second cohort: In 2 cities (Zanjan and Yazd) 20% of people (1200 people) receive a placebo after random allocation. The intervention involves an intramuscular injection of a dose of aluminum hydroxide on days 0, 28 and 56. This placebo is made by the Finlay Institute of Vaccines. Undecided - It is not yet known if there will be a plan to make this available Justification or reason for indecision in sharing IPD is There is no more information
public Dr. Ehsan Mostafavi
No. 69, 12 Farvardin St., Tehran
Tehran Iran (Islamic Republic of) 1316943551 +98 21 6411 2121 mostafaviehsan@gmail.com Pasture Institute of Iran scientific Dr. Hamid Emadi Kuchak
Enghela street, Tehran University of Medical Sciences
Tehran Iran (Islamic Republic of) 1467664961 +98 21 8897 3372 emadiham@tums.ac.ir Tehran University of Medical Sciences Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Giving written informed consent Ability to comply with the vaccination plan, scheduled visits and lab tests Having general health and controlled underlying diseases Iranian citizenship Residing in the studied cities (Isfahan, Babol, Bandar Abbas, Zanjan, Kerman, Hamedan, Yazd and Sari) Both Genders Aged 18 to 80 years 18 years 80 years Both Pregnant or lactating women or those who plan to become pregnant up to 3 months after the last dose of the vaccine Application of vaccines containing tetanus toxoid in the last 3 months History of blood /blood products transfusions such as immunoglobulin in the last three months Type 2 diabetes ( HbA1c higher than 7.5) Chronic liver disease (liver enzymes more than 5 times normal: ALT≥150, AST≥100) Subjects previously vaccinated against SARS-CoV-2. History of psychiatric disorders Uncontrolled asthma (having an asthma attack in the last three months). History of severe allergic reaction (anaphylaxis) to the vaccine throughout life History of smoking more than 20 cigarettes a day for more than twenty years Coagulation problems that contraindicate IM injection Previous vaccination with any coronavirus vaccine or participation in other COVID-19 vaccine trials Treatment with immunomodulators in the last 30 days Uncontrolled hypertension (cytological pressure more than 140, diastolic pressure more than 90 mm Hg) Fever or acute illness for 7 days before the injection or on the day of the injection Chronic kidney disease (GFR less than 30) All individuals who are in phase one priority of vaccination based on the National COVID-19 Vaccination Program (health workers can participate if they give consent) Subjects with tattoos in the deltoid region on both arms U11 Need for immunization against COVID-19 Prevention Placebo Prevention Placebo Intervention group in the first cohort: In 6 cities (Isfahan, Babol, Bandar Abbas, Sari, Kerman and Hamedan) 80% of people (14,400 people) receive the intervention (vaccine) after random allocation. Intervention is included intramuscular injection of vaccine candidates with conjugation of 25 μg RBD to tetanus toxin in a 2-dose program (days 0 and 28). This vaccine is made by the Finlay Institute of Vaccines. Control group in the first cohort: In 6 cities (Isfahan, Babol, Bandar Abbas, Sari, Kerman and Hamedan) 20% of people (3600 people) receive a placebo after random allocation. The intervention involves an intramuscular injection of a dose of aluminum hydroxide on days 0 and 28. This placebo is made by the Finlay Institute of Vaccines. Intervention group in the second cohort: In two cities (Zanjan and Yazd) 80% of people (4800 people) receive the intervention (vaccine) after random allocation. The intervention includes: a 2-dose program + a booster dose (days 0, 28, 56). The booster dose of the candidate vaccine is Sobrana Plus (50 micrograms d-RBD +, IM 0.5 ml). This vaccine is made by the Finlay Institute of Vaccines. Control group in the second cohort: In 2 cities (Zanjan and Yazd) 20% of people (1200 people) receive a placebo after random allocation. The intervention involves an intramuscular injection of a dose of aluminum hydroxide on days 0, 28 and 56. This placebo is made by the Finlay Institute of Vaccines. The effectiveness of the vaccine in preventing symptomatic Covid-19 infection. Timepoint: 2-dose regimen: Day 14 and 75 days after dose-2 injection; 2-dose + booster regimen: Day 14 after dose-2 injection and 90 days after booster. Method of measurement: Real Time PCR test results for COVID-19. Humoral safety will be studied on a subset of the population of Babol, Sari (under 2-dose regimen) and Zanjan (under 2-dose + booster regimen). Timepoint: The Humoral test will be done before and 1 month after receiving the last dose. Also, in Babol and Sari, an additional assessment will be done on days 5 and 28 of a 30% sample of subjects (900 people in each city). Method of measurement: EISA test. The frequency of local and systemic events and mild, moderate , severe, critical adverse events and death will be recorded by the participants in the forms. Timepoint: The occurrence of side effects and adverse events will be monitored from Zero day to 5 months after the injection of the last dose. Method of measurement: Active and inactive monitoring from Zero day to 5 months after the injection of the last dose with the registration of adverse events in CIFs. Evaluation of Cellular safety will be performed on 130 people in one of the cities of Babol or Sari (depending of logistic status). Timepoint: Cell immunoassay will be performed at the same time as the humoral tests. Method of measurement: Interferon Gamma Release Assay. The effectiveness of the vaccine in preventing severe form of Covid-19. Timepoint: 2-dose regimen: Day 14 and 75 days after dose-2 injection; 2-dose + booster regimen: Day 14 after dose-2 injection and 90 days after booster. Method of measurement: Based on the patient's clinical condition, like respiratory symptoms such as dyspnea and tachypnea, SpO2 of lower than 90%, and lung involvement of more than 50%, or hospitalization. The effectiveness of the vaccine in prevention of death from Covid-19. Timepoint: All cases of death due to COVID-19 will be detected: 2-dose regimen: Day 14 and 75 days after dose-2 injection; 2-dose + booster regimen: Day 14 after dose-2 injection and 90 days after the booster. Method of measurement: According to the diagnosis of the research physician and the DSMB team and based on the definition of the World Health Organization. SARS-CoV-2 virus neutralization assay. Timepoint: Based on serum samples on day 0 and up to 1 month after receiving the last dose of vaccine in 10% of antibody positive volunteers. Method of measurement: Viral neutralization tests (VNTs). Pasture Institute of Iran Approved 2021-04-17 National Committee for Ethics in Biomedical Research Sima-Ye-Iran St, Shahrak Gharb, Ministry o Health, Treatment and Medical Education Tehran Tehran Iran (Islamic Republic of)