Immunogenicity and Safety of a Booster Dose of the SpikoGen COVID-19 Vaccine

Study Overview
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Brief Summary
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This was a randomized, two-armed, double-blind, placebo-controlled trial designed to evaluate the safety and immunogenicity of a booster dose of an adjuvanted recombinant SARS-CoV-2 spike protein subunit vaccine (SpikoGen) produced by CinnaGen Co. A total of 300 adult individuals received a single dose of either the SpikoGen vaccine or the saline placebo in a 5:1 ratio at 4 to 9 months after the second dose of a COVID-19 vaccine of any type. The injection was given in the deltoid muscle of the non-dominant arm. On day 14, the trial was unblinded, and the participants in the placebo group received a booster dose of the SpikoGen vaccine. For immunogenicity assessments, blood samples were collected on days 0 and 14 from all participants and on days 90 and 180 from those in the vaccine group only. For safety assessments, all participants were followed up for six months. Study hypotheses included: A booster dose of the SpikoGen COVID-19 vaccine is safe and tolerable in adult subjects. A booster dose of the SpikoGen COVID-19 vaccine induces strong immunogenicity against SARS-CoV-2 in adult subjects.

Official Title
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A Randomized, Two-Armed, Placebo-Controlled, Double-Blind, Parallel-Group Clinical Trial to Evaluate the Immunogenicity and Safety of a Booster Dose of an Adjuvanted Recombinant Spike Protein COVID-19 Vaccine (SpikoGen)

Conditions
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COVID-19

Intervention / Treatment
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* Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant
* Biological: Saline placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 years Willing and able to comply with all study requirements, including scheduled visits, interventions, and laboratory tests Healthy adults or adults in a stable medical condition, defined as not being hospitalized within 3 months prior to the screening visit Subjects who have received two doses of a COVID-19 vaccine of any type between 4 to 9 months before the screening visit Exclusion Criteria: Subjects with signs of active SARS-CoV-2 infection at the screening visit or within 72 hours prior to the screening visit Subjects who have been diagnosed with a breakthrough infection after receiving two doses of a COVID-19 vaccine Subjects with epilepsy or a history of febrile seizures Subjects who receive immunosuppressive or cytotoxic medications. Subjects who have a history of severe allergic reactions (e.g., anaphylaxis) to the study vaccine, any components of the study interventions, or any pharmaceutical products. Subjects who have received any other investigational products within 30 days prior to the screening visit or intend to participate in any other clinical studies during the period of this study. Subjects who have received any vaccines within 28 days prior to the screening visit or intend to receive any vaccines up to day 14 of the study. Subjects who have any known bleeding disorders or, in the investigator's opinion, have any contraindications for an intramuscular injection. Female Subjects who are pregnant or breastfeeding or have planned to become pregnant within one month after the study injection. Subjects who have received any blood, plasma, or immunoglobulin products from 90 days prior to the screening visit or intend to receive during the study period. Subjects with any condition that may increase the risk of participating in the study or may interfere with the evaluation of the primary endpoints of the study in the investigator's opinion. Subjects who have donated ≥450 mL of blood or blood products within 28 days prior to the screening visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SpikoGen COVID-19 Vaccine<br> | Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant<br>* SARS-CoV-2 recombinant spike protein (25 µg) with Advax-SM adjuvant (15 mg); a single intramuscular injection into the deltoid muscle of the non-dominant arm<br>* Other names: COVAX-19;|
| Placebo Comparator: Saline Placebo<br> | Biological: Saline placebo<br>* 0.9% sodium chloride (1 mL); a single intramuscular injection into the deltoid muscle of the non-dominant arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies | As measured by ELISA | 14 days after the booster dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of solicited adverse events | Injection site pain, erythema, swelling, and induration, axillary swelling or tenderness ipsilateral to the side of injection, fever (oral temperature), headache, fatigue, myalgia, arthralgia, nausea, vomiting, and chills, as reported by the study participants on electronic diaries, and as defined using system organ classes and preferred terms of the Medical Dictionary for Regulatory Activities (MedDRA) | For 7 days after the booster dose | 
| Incidence of unsolicited adverse events | As reported by the study participants on electronic diaries, and as defined using system organ classes and preferred terms of the Medical Dictionary for Regulatory Activities (MedDRA) | For 14 days after the booster dose | 
| Incidence of serious adverse events (SAEs) and suspected unexpected serious adverse reaction (SUSARs) | As defined using system organ classes and preferred terms of the Medical Dictionary for Regulatory Activities (MedDRA) | For 6 months after the booster dose | 
| Geometric mean concentration (GMC) for S1 binding IgG antibodies | As measured by ELISA | Days 0, 14, 90, and 180 | 
| Geometric mean fold rise (GMFR) for S1 binding IgG antibodies | As measured by ELISA | 14 days after the booster dose | 
| Percentage of participants with seroconversion for S1 binding IgG antibodies | As measured by ELISA | 14 days after the booster dose | 
| Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgG antibodies | As measured by ELISA | 14 days after the booster dose | 
| Geometric mean concentration (GMC) for receptor-binding domain (RBD) binding IgG antibodies | As measured by ELISA | Days 0, 14, 90, and 180 | 
| Geometric mean fold rise (GMFR) for receptor-binding domain (RBD) binding IgG antibodies | As measured by ELISA | 14 days after the booster dose | 
| Geometric mean concentration (GMC) for SARS-CoV-2 neutralizing antibodies | As measured by ELISA | Days 0, 14, 90, and 180 | 
| Geometric mean fold rise (GMFR) for SARS-CoV-2 neutralizing antibodies | As measured by ELISA | 14 days after the booster dose | 
| Change in T-cell IFN-γ secretion from baseline to 14 days after the booster dose | As measured by IGRA | Days 0 and 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, SARS-CoV-2, Recombinant protein, Spike, Advax-SM, Advax, Vaccine, Adjuvant