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IRCT20230131057293N1 IRCT 2023-02-07 ReNAP Company Evaluation of safety and immunogenicity of mRNA-based COVID-19 vaccine (COReNAPCIN) in healthy population: Phase 1 study Phase I, Randomized, Double Blind, Placebo-controlled, Study of the Safety and Immunogenicity of mRNA-based COVID-19 Vaccine (COReNAPCIN) Produced by ReNAP Co. as Booster Dose in Healthy Population Aged 18-50 Years 2023-02-08 anticipated 30 Complete https://irct.ir/trial/68357 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Used, Assignment: Parallel, Purpose: Prevention, Other design features: In order to identify possible safety signals, vaccination will proceed in a staged fashion. Sentinel groups will be formed with 5 participants (4 subjects injected with COReNAPCIN and 1 subject injected with placebo). Subjects in sentinel groups will stay at the study center and be monitored for 48 hours after the injection. During this period, the injection site will be examined, vital signs and clinical symptoms will be evaluated at specific time intervals, and any adverse event will be documented. Participants in non-sentinel groups will stay at the study center for 2 hours after injection and will be monitored for vital signs and safety events. By comparing the data gathered from safety and immunogenicity assays during the study period, it will be determined which dose will be the right dose of COReNAPCIN to enter the next stages of development, Randomization description: The randomization process in this study will be done in four stages by creating a block randomization sequence (with odd units). In the first block, five participants will randomly be assigned to the sentinel group. Four subjects will receive a dose of 25 micrograms of COReNAPCIN and one subject will receive placebo intervention. In the second phase, after confirming the safety of 25 micrograms of COReNAPCIN in the sentinel group, 10 other participants will randomly be assigned to the study, of whom 8 subjects will receive a dose of 25 micrograms of COReNAPCIN and 2 subjects will receive placebo. For this purpose, two block sequences with size five are generated, including four subjects in the COReNAPCIN group and one subject in the placebo group. In the third phase, five participants will randomly be assigned to the second sentinel group. Four subjects will receive a dose of 50 micrograms of COReNAPCIN and one subject will receive placebo. In the fourth phase, after confirming the safety of 50 micrograms of COReNAPCIN in the sentinel group, 10 other participants will randomly be assigned to the study, of whom 8 subjects will receive a dose of 50 micrograms COReNAPCIN and 2 subjects will receive placebo. For this purpose, two block sequences with size five are generated, including four subjects in the COReNAPCIN group and one subject in the placebo group. Random codes will be generated by R-CRAN software version 4.0.1, Blinding description: In this study, the participants' group and the type of intervention they receive will not be disclosed. The site personnel, including the principal investigator, co-investigator, and study team, will be unaware of the type of intervention (COReNAPCIN or placebo) administered to each participant. This is especially important for those who evaluate participants' safety. Vials of vaccine and placebo have the same research label (contains unique blinding codes) and syringes will be relabeled in the same way during intervention preparation so that the person who injects interventions and the participants will not be aware of the type of intervention. An unblinded person is present in the study who holds the randomization list and will assign randomization codes to subjects. This person will not participate in other parts of this clinical study. Randomization information will be stored in opaque sealed envelopes at the study center and in a place with limited access. 1 COVID-19. Intervention 1: Intervention group 1: a single dose of 25 μg/0.25 ml of COReNAPCIN vaccine (Produced by ReNAP Co.) on day 1, which is received intramuscularly (deltoid muscle). COReNAPCIN is an mRNA vaccine encapsulated by lipid nanoparticles (LNP), containing mRNA encoding the spike protein of the SARS-CoV-2 virus. Intervention 2: Intervention group 1: a single dose of 50 μg/0.5 ml of COReNAPCIN vaccine (Produced by ReNAP Co.) on day 1, which is received intramuscularly (deltoid muscle). COReNAPCIN is an mRNA vaccine encapsulated by lipid nanoparticles (LNP), containing mRNA encoding the spike protein of the SARS-CoV-2 virus. Intervention 3: Control group: single dose of normal saline (0.9% sodium chloride solution for injection), (0.25 or 0.5 ml) on day 1, which is received intramuscularly (deltoid muscle). 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 Undecided - It is not yet known if there will be a plan to make this available
public Maryam Badri
Unit 2, No. 14, 16th St., South Gandhi Ave.
Tehran Iran (Islamic Republic of) 1517854313 +98 21 8866 0795 info@ppvcro.com Pharmed Pajoohan Viera scientific Mohamadreza Salehi
Imam Khomeini Hospital complex, Dr Gharib Ave,. Keshavarz Blvd.
Tehran Iran (Islamic Republic of) 1419733141 +98 21 6119 2811 Salehi.mohamad3@gmail.com Tehran University of Medical Sciences Iran (Islamic Republic of) Provides written informed consent prior to initiation of any study procedures Be able to understand the purpose and risks of the study and willing and able to comply with planned study procedures and be available for all study visits Agrees to perform all study procedures, including the collection of venous blood per protocol 18 to 50 years of age, inclusive Body Mass Index 18-35 kg/m2 Women of childbearing potential must agree to use a reliable method of contraception from the time of enrollment until sixty days after receiving the intervention and negative urine or serum pregnancy test within 24 hours prior to intervention administration Male subjects of childbearing potential with a female partner of childbearing potential agree to use effective contraception from intervention through 60 days after Male subjects agree to refrain from sperm donation from the time of intervention through 60 days after In good health as determined by medical history and physical examination and the opinion of the principal investigator Has received 3 doses of inactivated Sinopharm or COVIran Barekat vaccine and the time interval from receiving the last dose of vaccine to receiving clinical study intervention at least 90 days and maximum 18 months, vaccination history must be checked and approved through the vaccination record Normal vital signs at the screening visit and at the time of intervention including: temperature less than 38.0 °C; pulse no greater than 100 beats per minute; systolic blood pressure 90 to 140 mmHg and diastolic blood pressure 60 to 90 mmHg; Oxygen saturation≥ 95%; respiration rate 12 to 20 BPM Clinical screening laboratory evaluations (WBC, Hgb, PLTs, ALT, AST, BUN, Cr, ALP, T.Bili, Lipase, PT, PTT, TSH, T4, FBS, and CRP) are within acceptable normal reference ranges Agree to refrain from donating blood or plasma during the study (outside of this study) 18 years 50 years Both Positive pregnancy test either at screening or just prior to intervention administration Female subject who is breastfeeding or plans to breastfeed from the time of intervention through 60 days after Has any medical disease or condition that, in the opinion of the principal investigator, precludes study participation Presence of self-reported or medically documented significant medical (including respiratory, cardiovascular, neurological, autoimmune, Immunodeficiency, and kidney diseases...) or psychiatric condition Has an acute illness within 2 weeks prior to injection, with or without fever [temperature ≥38.0°C], runny nose or eyes, shortness of breath, cough, weakness, and diarrhea, that in the opinion of the principal investigator, precludes study participation Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or HIV types 1 or 2 antibodies Has participated in another investigational study involving any investigational product (study drug, biologic, or device) within 60 days, or 5 half-lives, whichever is longer, before intervention administration Currently enrolled in or plans to participate in another clinical trial during the study period Has previously participated in an investigational study involving lipid nanoparticles (LNPs) Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to any components of the study product, any previous licensed or investigational vaccines or medication, and to any food or cosmetics History of using any medication that, in the opinion of the principal investigator or the study pharmacotherapist, may be associated with impaired immune responsiveness Anticipating the need for immunosuppressive treatment within Within 6 months after study enrollment Received immunoglobulins and/or any blood or blood products within the 4 months before intervention administration or the possible need to use at any time during the study Has any blood dyscrasias or significant disorder of coagulation Has any chronic liver disease, including fatty liver Has a history of alcohol abuse or other recreational drug use within 6 months before intervention administration Has a positive test result for drugs of abuse at screening Has any abnormality or permanent body art (e.g., tattoo) that would interfere with the ability to observe local reactions at the injection site (deltoid region) Received or plans to receive a licensed, live vaccine within 4 weeks before or after intervention administration Received or plans to receive a licensed, inactivated vaccine within 2 weeks before or after intervention administration History of clinical or virological diagnosis of COVID-19 within 3 months before intervention administration Positive SARS-CoV-2 or influenza PCR test from nasopharyngeal swab at the screening visit, with a maximum time interval of 48 hours between taking the test and intervention administration History of receiving medication to prevent COVID-19 within 3 months before intervention administration On current treatment with investigational agents for prophylaxis of COVID-19 Current use of any prescription or over-the-counter medications within 7 days prior to intervention administration, unless approved by the investigator or necessary to manage a chronic condition Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection Plan to travel outside Iran from enrollment through 28 days after intervention administration Reside in a nursing home or other skilled nursing facility or have a requirement for skilled nursing care Non-ambulatory Recent (within the last 12 months) use of a dermal filler History of thrombosis Vulnerable groups and foreigners U07.1 COVID-19, virus identified Prevention Prevention Placebo Intervention group 1: a single dose of 25 μg/0.25 ml of COReNAPCIN vaccine (Produced by ReNAP Co.) on day 1, which is received intramuscularly (deltoid muscle). COReNAPCIN is an mRNA vaccine encapsulated by lipid nanoparticles (LNP), containing mRNA encoding the spike protein of the SARS-CoV-2 virus. Intervention group 1: a single dose of 50 μg/0.5 ml of COReNAPCIN vaccine (Produced by ReNAP Co.) on day 1, which is received intramuscularly (deltoid muscle). COReNAPCIN is an mRNA vaccine encapsulated by lipid nanoparticles (LNP), containing mRNA encoding the spike protein of the SARS-CoV-2 virus. Control group: single dose of normal saline (0.9% sodium chloride solution for injection), (0.25 or 0.5 ml) on day 1, which is received intramuscularly (deltoid muscle). Reactogenicity. Timepoint: During 1 hour after intervention administration. Method of measurement: History checking and examination including injection site examination, clinical and vital signs monitoring, participant reports. Frequency and grade of each solicited local and systemic adverse event. Timepoint: From day 1 (intervention administration) to 7 days after. Method of measurement: History checking and examination including injection site examination, clinical and vital signs monitoring, and participant reports. Frequency and grade of any unsolicited AEs. Timepoint: From day 1 (intervention administration) to 28 days after. Method of measurement: History checking and examination including injection site examination, clinical and vital signs monitoring, participant reports, Clinical laboratory evaluations. Frequency of Serious Adverse Events (SAEs). Timepoint: from Day 1 (intervention administration) to Day 181. Method of measurement: History checking and examination in follow-up visits, participant reports, Clinical laboratory evaluations. Frequency of New Onset Chronic Medical Conditions (NOCMCs). Timepoint: from Day 1 (intervention administration) to Day 181. Method of measurement: History checking and examination in follow-up visits, participant reports, Clinical laboratory evaluations. Frequency of Medically Attended Adverse Event (MAAEs). Timepoint: from Day 1 (intervention administration) to Day 181. Method of measurement: Participant reports. IgG assay to the SARS-CoV-2 S (spike) protein by ELISA method. Timepoint: Days 1, 8, 15, 29, 91, 181. Method of measurement: Geometric mean titer (GMT) of antibody; Percentage of subjects who seroconverted (4-fold increase in antibody titer over baseline); The geometric mean fold rise (GMFR) in IgG titer from baseline. IgG assay to the SARS-CoV-2 receptor-binding domain (RBD) protein by ELISA method. Timepoint: Days 1, 8, 15, 29, 91, 181. Method of measurement: Geometric mean titer (GMT) of antibody; Percentage of subjects who seroconverted (4-fold increase in antibody titer over baseline); The geometric mean fold rise (GMFR) in IgG titer from baseline. Neutralizing antibodies assay (cVNT test). Timepoint: Days 1 and 15. Method of measurement: Geometric mean titer (GMT) of neutralizing antibody at each timepoint; Percentage of subjects who seroconverted (4-fold increase in antibody titer over baseline); The geometric mean fold rise (GMFR) in neutralizing antibody titer from baseline. Evaluation of specific T-cell responses. Timepoint: Days 1 and 15. Method of measurement: Percentage of specific CD4+ and CD8+ lymphocytes producing IFN-Y and IL-4 cytokines measured by flow cytometry. Evaluating the response of peripheral blood lymphocytes to vaccination. Timepoint: Days 1, 8, 15, 29. Method of measurement: Percentage of CD3+, CD4+, CD8+ T cells, B cells and NK cells by Flow cytometry. Measurement of serum levels of cytokines IL-10, IL-17, IL-4, IL-2, IL-6, IL-1B, TNF-α, IFN-γ. Timepoint: Days 1, 8, 15, 29. Method of measurement: ELISA method. ReNAP Company Approved 2023-01-25 Iran National Committee for Ethics in Biomedical Research Ministry of Health & Medical Education Headquarters, Between Zarafashan & South Falamak, Sima-ye-Iran St., Qods Town Tehran Tehran Iran (Islamic Republic of)