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IRCT20201214049709N3 IRCT 2021-08-29 Razi Vaccine and Serum Research Institute Comparison of the safety and efficacy of Razi SARS-CoV-2 recombinant Spike protein (Razi Cov Pars) and Sinopharm vaccines Comparison of the safety and efficacy of Razi SARS-CoV-2 recombinant Spike protein (Razi Cov Pars) and Sinopharm vaccines in adults aged 18 and over, a phase III randomised, double blind, non-inferiority clinical trial 2021-09-01 anticipated 41128 Complete https://irct.ir/trial/58143 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Parallel, Purpose: Prevention, Other design features: In addition to the randomized arms, two non-randomised and open label arms were added to the study. Participants will receive one of the Razi or Sinofarm vaccines by their own choice in these additional arms, Randomization description: This study uses both randomized and non-randomized arms. Block randomization method with variable block sizes of 4 and 6 in STATA will be used to create the random sequence in randomized arms. For the purpose of concealment, a unique code will be assigned to each intervention the participants receive, and all subjects will be identified with this code until the end of the study (concealment code), Blinding description: In this study, the control group will receive the Sinopharm vaccine, which has different color, volume and packaging from Razi Cov Pars. Therefore, blinding will be performed by a person who will be responsible for preparing and inoculating the vaccine. This is the only person who will not be blind to the intervention given. Once the participant becomes eligible to receive the vaccine, a concealment/randomization code will be assigned to the volunteer and the vaccine type will be displayed on the screen of the vaccinator until the inoculation is confirmed. To protect the blinding in the participant, the syringe's cylinder will be covered to conceal the content of the syringe. Non-randomized arms that were added to the study later on, are not blind. 3 Acute Respiratory Distress Syndrome due to SARS-CoV-2. Intervention 1: Intervention group1: Participants in this group will receive two doses (IM) of RAZI recombinant spike protein vaccine 21 days apart followed by a nasal spray 51 days after the first dose (day 0). Intervention 2: Intervention group2: Participants in this group will receive two doses (IM) of Sinopharm vaccine 21 days apart followed by a nasal spray 51 days after the first dose (day 0). Nasal spray contains an adjuvant made in Razi Institute. https://www.sciencedirect.com/science/article/pii/S2405844024034017 Background: We conducted a phase III, non-inferiority trial comparing safety and efficacy of RCP recombinant spike protein Covid-19 vaccine to BBIBP (Sinopharm). Methods: Adult Iranian population received RCP or BBIBP in a randomized, double blind and an additional non-randomized open labeled trial arms. Eligible participants signed a written informed consent and received two intramuscular injections three weeks apart. In the randomized arm, an intranasal dose of vaccine or adjuvant-only preparation were given to the RCP and BBIBP recipients at day 51 respectively. Participants were actively followed for up to 4 months for safety and efficacy outcomes. Primary outcome was PCR + symptomatic Covid-19 disease two weeks after the second dose. The non-inferiority margin was 10% of reported BBIBP vaccine efficacy (HR = 1.36). Results: We recruited 23,110 participants (7224 in the randomized and 15,886 in the nonrandomized arm). We observed 604 primary outcome events during 4 months of active followup including 121 and 133 in the randomized and 157 and 193 cases in the non-randomized arms among recipients of RCP and BBIBP respectively. Adjusted hazard ratios for the primary outcome in those receiving RCP compared with BBIBP interval were 0.91 (0.71–1.16) and 0.62 (0.49–0.77) in the randomized and non-randomized arms respectively. The upper boundary of 99.1% confidence interval of HR = 0.91 (0.67–1.22) remained below the margin of noninferiority in the randomized arm after observing the early stopping rules using O’Brien Fleming method. Conclusion: Our study showed that the RCP efficacy is non-inferior and its safety profile is comparable to the BBIBP. Yes - There is a plan to make this available What will be shared: Deidentified IPD related to outcome will be shared. When: The access period will begin once the study is complete and the main results have been published in peer reviewed journals. To whom: The data that have been published in peer reviewed journals, will be available just for academic researchers. Conditions: The proposed study protocol should be submitted to RAZI vaccine and serum research institute and approved by its scientific and technical advisory committee. Where to obtain: Researchers will submit their request to Dr. Mohammad Hossein Fallah at the following email address (mhf2480@yahoo.com ) How to obtain: Data will be made available after consideration and approval by the relevant authorities from Razi Vaccine and Serum Research Institute. Comments:
public Mohammad Hossein Fallah Mehrabadi
Hesarak - Shahid Beheshti street- Karaj
Karaj Iran (Islamic Republic of) 3197619751 +98 26 3457 0038 mhf2480@yahoo.com Razi Vaccine and Serum Research Institute scientific Dr Saeid Kalantari
Corner of Mansouri, Niayesh, Satarkhan Av, Tehran
Tehran Iran (Islamic Republic of) ۱۴۴۵۶۱۳۱۳۱ +98 21 6435 1000 kalantari.s@iums.ac.ir Iran University of Medical Sciences Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) 18 years of age or older; Having access to internet and smart phone; No current COVID-19; No pregnancy; No plan to have children in the next 6 months and willing to use at least one effective method of contraception; Signed informed consent form. 18 years no limit Both Any current or new diagnosis of acute or chronic illness requiring continuous ongoing medical care Breastfeeding; History of receiving any COVID -19 vaccine; Received blood and/or any blood products and/or immunoglobulins within three months preceding the screening day; Long-term use of immunosuppressive drugs or systemic corticosteroids within the past 4 months; History of allergic diseases such as angioedema or anaphylactic reactions to any drug, vaccine or food; Recent diagnosis or treatment of cancers except basal cell carcinoma and In-situ cervical cancer History of uncontrolled serious psychiatric illnesses; History of blood disorders (dyscrasia, coagulopathy, platelet deficiency or disorder, or deficiency of blood clotting factors); History of chronic neurological diseases (including seizures and epilepsy); Current substance or alcohol abuse; Splenectomy for any reason; Close contact with a confirmed COVID-19 case within two weeks before the first vaccine dose; History of diagnosis or treatment for HIV; Chronic unstable diseases in the last 4 weeks, including hospitalization due to surgery, deterioration of one organ function, the need to add new drugs or serious dose adjustments to existing drugs. U07.1 COVID-19, virus identified Prevention Prevention Intervention group1: Participants in this group will receive two doses (IM) of RAZI recombinant spike protein vaccine 21 days apart followed by a nasal spray 51 days after the first dose (day 0). Intervention group2: Participants in this group will receive two doses (IM) of Sinopharm vaccine 21 days apart followed by a nasal spray 51 days after the first dose (day 0). Nasal spray contains an adjuvant made in Razi Institute. Occurrence of any symptomatic confirmed COVID-19 disease: Number and percentage of confirmed COVID-19 disease two weeks after second vaccine dose. Timepoint: Any time between the 14 days after second vaccine dose and the end of study. Method of measurement: Diagnosis of COVID-19 disease will be based on Iran's Ministry of Health's guideline and a positive PCR test. Occurrence of confirmed moderate or severe illness or death due to COVID-19: Number and percentage of moderate, severe illness or death due to COVID-19. Timepoint: Any time, two weeks after the second dose until the end of study. Method of measurement: PCR test and Clinical evaluations. Severity of Covid-19 will be classified according to NIH criteria. Occurrence of confirmed severe illness or death due to COVID-19: Number and percentage of severe illness or death due to COVID-19. Timepoint: Any time, two weeks after the second dose until the end of study. Method of measurement: PCR test and Clinical evaluations. Severity of Covid-19 will be classified according to NIH criteria. Abnormal vital signs and anaphylactic reactions up to 30 minutes after vaccination: number and percentages of participants who develop abnormal vital signs within half an hours of receiving the vaccine at each doses will be recorded. Abnormal vital signs include temperature, respiratory rate, heart rate, systolic and diastolic blood pressure. Anaphylaxis is defined as systemic hypersensitivity with at least two of the following signs and symptoms: erythema, pruritus, urticaria and angioedema, bronchospasm, laryngeal edema, dizziness, hypotension, nausea, shortness of breath, wheezing, arrhythmia, cyanosis, vomiting, diarrhea, abdominal pain. Timepoint: Immediately and up to half an hours after vaccination. Method of measurement: Clinical examination. Local adverse events within the first week post-vaccination: including pain, tenderness, erythema or redness, swelling and stiffness that will be assessed based on the severity score, duration and peak intensity. Timepoint: Daily assessment up to six days following 1st and 2nd vaccine dose. Method of measurement: They will be assessed through e-Diary card. This card is provided in the mobile application. Systemic adverse events within the first week post-vaccination: including nausea and vomiting, diarrhea, headache, fatigue, muscle pain that will be assessed based on the severity score, duration and peak intensity. Timepoint: Daily assessment up to six days following each vaccine dose. Method of measurement: They will be assessed through e-Diary card. This card is provided in the mobile application. Serious adverse events (SAEs), Suspected Unexpected Serious Adverse Reaction (SUSARs), Medically Attended Adverse Events (MAAEs), up to 6 month after 2nd vaccine dose. Timepoint: Weekly until the end of study. Method of measurement: In the form of weekly questions and through the mobile phone application. Specific secretory IgA level: This will be measured in a subgroup of participants in saliva and blood samples. Timepoint: two week after receiving the intranasal dose. Method of measurement: Elisa. Razi Vaccine and Serum Research Institute Approved 2021-08-24 National Research Ethics Committee Floor 13, Block A, Ministry of Health & Medical Education Headquarters, Between Zarafashan & South Falamak, Qods Town, Tehran, Iran. Tehran Tehran Iran (Islamic Republic of)