Protocol summary
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Study aim
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Evaluating Immunogenicity and safety of recombinant SARS-COV-2-S protein
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Design
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A phase II, randomized, two-armed, double-blind, placebo controlled clinical trial with 400 subjects. Stratified randomization by R-CRAN-version 4.0.1
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Settings and conduct
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randomized, two-armed, double-blind, placebo controlled clinical trial in Espinas Palace Hotel, Tehran
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Participants/Inclusion and exclusion criteria
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inclusion:Individuals≥18 years.who are willing and able to comply with study requirements.Healthy and stable medical conditions.Women who are not pregnant/breastfeeding.exclusion:Subjects with active infection with signs of SARS-COV-2.Subjects with temperature ≥38◦C at screening or 72hrs prior.Progressive/severe neurological disorder,seizures,history of Guillain-Barre syndrome.who receive immunosuppressive medications.Pregnant/breastfeeding or women who become pregnant during the study.People with history of severe adverse reactions to the study vaccine.who participated in clinical trials within 30 days before screening until end of the study.who have previously vaccinated against SARS-CoV-2.who received other authorized vaccines within 28 days prior to the screening/intend to receive vaccine up to 14 days after second dose.People with known bleeding disorder.who received/intend to receive any blood/blood products 90 days or donated ≥450ml 28 days prior to screening
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Intervention groups
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Intervention:1 IM injection of 25 ug subunit vaccine with Advax-CpG adjuvant on day 0 and 21
Placebo:1 IM injection of normal saline (0.9% saline) on day 0 and 21
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Main outcome variables
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solicited adverse events up to 7 days after each dose.
unsolicited adverse events up to 28 days after each dose
Evaluation and comparison of individuals with seroconversion for IgG bAb against S protein on days 21 and 35.
GMT measurement for IgG binding antibody (bAb) against protein S on days 0, 21 and 35
General information
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Reason for update
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20150303021315N23
Registration date:
2021-05-24, 1400/03/03
Registration timing:
prospective
Last update:
2021-07-08, 1400/04/17
Update count:
1
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Registration date
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2021-05-24, 1400/03/03
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2021-05-29, 1400/03/08
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Expected recruitment end date
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2021-07-22, 1400/04/31
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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A phase II, Randomized, Two-armed, Double-blind, Placebo controlled trial to evaluate efficacy and safety of an adjuvanted recombinant SARS-CoV-2 spike (S) protein subunit vaccine (SpikoGen®) produced by CinnaGen Co. (Two doses of 25µg with dosing interval of 21 days)
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Public title
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evaluate efficacy and safety of SpikoGen® vaccine on healthy adults to prevent COVID-19 disease
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Purpose
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Prevention
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Inclusion/Exclusion criteria
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Inclusion criteria:
Men or women ≥18 years
Participants who are willing and able to comply with study requirements, including all scheduled visits, vaccinations and tests
Healthy adults or adults with stable medical conditions.
Women eligible to participate in the study who are not pregnant or breastfeeding.
Exclusion criteria:
Subjects with active infection with SARS-COV-2 signs at the screening visit.
Subjects with body temperature equal or more than 38 degrees centigrade, during 72 hours before screening visit or at the visit.
Subjects with any progressive or severe neurological disorder, seizures, or a history of Guillain-Barre syndrome.
Subjects who receive immunosuppressive or cytotoxic medications.
Pregnant women, or breastfeeding mothers, or women who plan to become pregnant during the study.
Subjects who have a history of severe allergic reactions (e.g. anaphylaxis) to the study vaccine or any components of the vaccine or any other drugs.
Subjects who have received any other investigational product within 30 days prior to the screening visit or intend to participate in other clinical studies during this trial.
Subjects who have been vaccinated with other vaccines against the SARS-CoV-2 virus.
Subjects who received other authorized vaccines within 28 days prior to the screening visit in this study or intend to receive any vaccines up to 14 days after the second vaccination.
Subjects who have any known bleeding disorder or may have problems with the intramuscular injection according to the researcher's opinion.
Subjects who have received or intend to receive any blood / plasma or immunoglobulin products 90 days prior to the screening visit.
Subjects with special circumstances who, may increase the risk of participating in the study or interfering with the evaluation of the primary endpoints of the study according to researcher's opinion.
Subjects who have donated ≥450 ml of blood or blood products 28 days prior to the screening visit.
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Age
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From 18 years old
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Gender
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Both
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Phase
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2
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Groups that have been masked
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- Participant
- Care provider
- Investigator
- Outcome assessor
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Sample size
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Target sample size:
400
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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Eligible patients will be assigned to treatment using a stratified randomization by R-CRAN-version 4.0.1. Randomization will be stratified according to two factors:
1. Age (Below the age of 65 – 65 and above)
2. High risk and low risk adults below the age of 65
After randomization procedure, a code will be allocated to each patient that will be used as patient identifier throughout the study. The assigned code will be denoted by 4 initials (corresponding to the first two letters of first name, first two letters of surname) and 3 numbers (center code). Moreover, the described code is followed by study unique identification code consisting of first three letters of the generic name of the investigational product, i.e. VAC and five numbers (corresponding to the randomization number), e.g. ABCD001VAC-00001.
Each vaccine syringe has a unique code that differs from the rest of the vaccines. The CRO is responsible for preparing the unique codes. Therefore, only the CRO knows each code for the vaccine (manufactured by CinnaGen) or placebo (0.9% normal saline). In case of enrollment, each subject will be given a randomization code and will be assigned to one of the groups. During each visit, a vaccine with a specific code will be given to the subject. The CRO will monitor how subjects are assigned to the treatment groups.
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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The vaccine and the placebo have the same research label and are suitable for the vaccine boxes and syringes. The contents of the labels are based on EMA regulation. The SpikoGen® vaccine or placebo are packaged in the same way. Unique codes are printed on the vaccine and placebo labels, and each vaccine is linked to the participant through this unique code Participants and medical staff are not aware of the vaccine or placebo. The type of participants group and the type of vaccine they received will not be known for investigators and will be stored in opaque sealed envelopes at the center. Decoding or blind breaking, under special circumstances, is the responsibility of the DSMB Committee. Decoding for a participant is done by the investigator of the center, when all of the possibilities in the occurrence of the event are evaluated and rejected. The vaccine or the placebo is recognized as the most important factor in the occurrence of an event or management of its complications which lead to special treatment for the participant and a decision that is not possible without decoding.
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Placebo
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Used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2021-05-22, 1400/03/01
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Ethics committee reference number
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IR.NREC.1400.002
Health conditions studied
1
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Description of health condition studied
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COVID-19
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ICD-10 code
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U07.1
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ICD-10 code description
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COVID-19, virus identified
Primary outcomes
1
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Description
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Occurrence of solicited adverse events
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Timepoint
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Up to 7 days after each dose
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Method of measurement
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Checkup, history checking and participants reports based on adverse event reporting system
2
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Description
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Occurrence of unsolicited adverse events.
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Timepoint
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Up to 28 days after each dose.
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Method of measurement
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Checkup, history checking and participants reports based on adverse event reporting system
3
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Description
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Evaluation of seroconversion for IgG against S protein
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Timepoint
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On days 21 and 35
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Method of measurement
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ELISA and statistical analysis
4
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Description
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GMC measurement for IgG-binding antibody (bAb) against protein S
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Timepoint
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On days 0, 21 and 35
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Method of measurement
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ELISA and statistical analysis
Secondary outcomes
1
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Description
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Evaluation of seroconversion for nAb against SARS-CoV-2
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Timepoint
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Days 21 and 35
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Method of measurement
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sVNT (by ELISA) and statistical analysis
2
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Description
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Evaluation of seroconversion for IgA against RBD
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Timepoint
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Days 21, 35
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Method of measurement
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ELISA test and statistical analysis
3
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Description
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Evaluation of seroconversion for IgA against S protein
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Timepoint
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Days 21, 35
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Method of measurement
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ELISA test and statistical analysis
4
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Description
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Evaluation of seroconversion for IgG against RBD
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Timepoint
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Days 21, 35
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Method of measurement
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ELISA test and statistical analysis
5
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Description
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Evaluating GMC of bAb (IgG) against RBD
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Timepoint
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Days 0, 21, 35
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Method of measurement
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ELISA test and statistical analysis
6
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Description
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Evaluating GMFR of bAb (IgG) against S protein
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Timepoint
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Days 21, 35
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Method of measurement
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ELISA test and statistical analysis
7
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Description
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Evaluating GMFR of bAb IgG against RBD
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Timepoint
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Days 21, 35
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Method of measurement
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ELISA test and statistical analysis
8
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Description
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Evaluating GMC of nAb against SARS-COV-2
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Timepoint
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Days 0, 21, 35
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Method of measurement
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ELISA test and statistical analysis
9
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Description
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Evaluating GMFR of nAb against SARS-COV-2
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Timepoint
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Days 21, 35
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Method of measurement
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ELISA test and statistical analysis
10
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Description
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Evaluating cellular immune response by measuring proliferation percentage of CD4/CD8 lymphocytes
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Timepoint
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Days 0, 21, 35
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Method of measurement
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Flow cytometry
11
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Description
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incidence of SAEs and SUSARs
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Timepoint
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During 6 months after second dose
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Method of measurement
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Checkup, history checking and participants reports based on adverse event reporting system
12
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Description
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ٍEvaluation of cell proliferation (percentage of CD4 and CD8 cells) producing interferon-gamma after exposure to specific antigen, 25% of sample size (100 patients)
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Timepoint
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On days 0, 21, 35
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Method of measurement
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Intracellular Cytokine Staining and Flow cytometry
13
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Description
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nAb titer measurement against SARS-CoV-2
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Timepoint
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Days 21 and 35
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Method of measurement
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cVNT and statistical analysis
14
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Description
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Evaluating GMC of IgA against S protein
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Timepoint
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Days 0, 21, 35
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Method of measurement
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ELISA test and statistical analysis
15
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Description
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Evaluating GMFR of IgA against S protein
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Timepoint
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Days 21, 35
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Method of measurement
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ELISA test and statistical analysis
Intervention groups
1
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Description
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Intervention group: Injecting one dose of 1 ml solution of SpikoGen® vaccine containing recombinant SARS-CoV-2-S protein and Advax™ and CpG adjuvants in the non-dominant arm on days 0 and 21
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Category
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Prevention
2
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Description
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Control group: Injecting one dose of 1 ml placebo containing normal saline (0.9% NaCl solution) in non-dominant arm on days 0 and 21
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Category
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Placebo
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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CinnaGen Company
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Proportion provided by this source
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100
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Public or private sector
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Private
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Industry
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Undecided - It is not yet known if there will be a plan to make this available
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Study Protocol
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Yes - There is a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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Not applicable
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Data Dictionary
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Not applicable
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Title and more details about the data/document
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Participants' data will be available for regulatory and ethics committee for decisions.
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When the data will become available and for how long
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Documents including study protocol and the results will be available to the public after the study ends.
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To whom data/document is available
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The regulatory body and the ethics committee will have access to the study data. The monitoring team will have access to the study data during the conduct. DSMB will have access to the study data and results in predefined timelines and decides about the continuation of the study.
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Under which criteria data/document could be used
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With the permission of the sponsor and the approval of regulatory
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From where data/document is obtainable
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The study sponsor is responding to this request
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What processes are involved for a request to access data/document
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After contacting the principal investigator and obtaining permission from the sponsor
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Comments
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