Phase II Clinical Trial of CinnaGen COVID-19 Vaccine (SpikoGen)

Study Overview
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Brief Summary
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This is a phase II, randomized, two-armed, double-blind, placebo-controlled trial designed to evaluate the safety, tolerability, and immunogenicity of a candidate adjuvanted recombinant SARS-CoV-2 spike (S) protein subunit vaccine (SpikoGen) produced by CinnaGen Co. 400 adult individuals receive either SARS-CoV-2 recombinant spike protein (25 µg) with Advax-SM adjuvant (15 mg) or saline placebo in a 3:1 ratio. The injection is given in two doses with a 21-day interval in the deltoid muscle of the non-dominant arm. The randomization was stratified by age (<65 or ≥65) and health conditions of potential risk for severe COVID-19. Participants will be visited at two weeks and will be followed up for six months after the second dose of the study intervention. Study hypotheses include: The adjuvanted COVID-19 vaccine candidate is safe and tolerable in adult subjects. The adjuvanted COVID-19 vaccine candidate induces strong immunogenicity against SARS-CoV-2 in adult subjects.

Official Title
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A Phase II, Randomized, Two-armed, Double-blind, Placebo-controlled Trial to Evaluate the Safety, Tolerability, and Immunogenicity of an Adjuvanted Recombinant SARS-CoV-2 Spike (S) Protein Subunit Vaccine Candidate (SpikoGen)

Conditions
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Covid19

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 Females must not be pregnant or breastfeeding Exclusion Criteria: Subjects with signs of active SARS-COV-2 infection at the screening visit. Subjects with body temperature of 38 degrees Celsius or greater at the screening visit or within 72 hours prior to the screening visit. Subjects with a history of any progressive or severe neurological disorders, seizure, or Guillain-Barre syndrome. Subjects who receive immunosuppressive or cytotoxic medications. Female Subjects who are pregnant or breastfeeding or have planned to become pregnant during the study period. 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 been vaccinated with any vaccine or vaccine candidate against SARS-CoV-2. Subjects who have received any vaccines within 28 days prior to the screening visit or intend to receive any vaccines up to 14 days after the second dose of the study injection. Subjects who have any known bleeding disorders or, in the investigator's opinion, have any contraindications for an intramuscular 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: Vaccine candidate<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) in two doses with a 21-day interval administered with intramuscular injections in the non-dominant arm<br>* Other names: SpikoGen;|
| Placebo Comparator: Saline placebo<br> | Biological: Saline placebo<br>* 0.9% sodium chloride (1 mL) injection in two doses with a 21-day interval administered with intramuscular injections in the non-dominant arm<br>* Other names: Normal saline;|

What is the study measuring?
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Primary 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 each 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 28 days after each dose | 
| Percentage of participants with seroconversion for S1 binding IgG antibodies after the first injection | As measured by ELISA | 21 days after the first dose (on the day of the second dose) | 
| Percentage of participants with seroconversion for S1 binding IgG antibodies after the second injection | As measured by ELISA | 14 days after the second dose | 
| Change in geometric mean concentration (GMC) for S1 binding IgG antibodies from baseline to 21 days after the first injection | As measured by ELISA | On the day of the first dose and 21 days after the first dose (on the day of the second dose) | 
| Change in geometric mean concentration (GMC) for S1 binding IgG antibodies from baseline to 14 days after the second injection | As measured by ELISA | On the day of the first dose and 14 days after the second dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies after the first injection | As measured by ELISA (sVNT) | 21 days after the first dose (on the day of the second dose) | 
| Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies after the first injection | As measured by cVNT | 21 days after the first dose (on the day of the second dose) | 
| Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies after the second injection | As measured by ELISA (sVNT) | 14 days after the second dose | 
| Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies after the second injection | As measured by cVNT | 14 days after the second dose | 
| Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgA antibodies after the first injection | As measured by ELISA | 21 days after the first dose (on the day of the second dose) | 
| Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgA antibodies after the second injection | As measured by ELISA | 14 days after the second dose | 
| Percentage of participants with seroconversion for S1 binding IgA antibodies after the first injection | As measured by ELISA | 21 days after the first dose (on the day of the second dose) | 
| Percentage of participants with seroconversion for S1 binding IgA antibodies after the second injection | As measured by ELISA | 14 days after the second dose | 
| Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgG antibodies after the first injection | As measured by ELISA | 21 days after the first dose (on the day of the second dose) | 
| Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgG antibodies after the second injection | As measured by ELISA | 14 days after the second dose | 
| Change in geometric mean concentration (GMC) for receptor-binding domain (RBD) binding IgG antibodies from baseline to 21 days after the first injection | As measured by ELISA | On the day of the first dose and 21 days after the first dose (on the day of the second dose) | 
| Change in geometric mean concentration (GMC) for receptor-binding domain (RBD) binding IgG antibodies from baseline to 14 days after the second injection | As measured by ELISA | On the day of the first dose and 14 days after the second dose | 
| Geometric mean fold rise (GMFR) for S1 binding IgG antibodies after the first injection | As measured by ELISA | 21 days after the first dose (on the day of the second dose) | 
| Geometric mean fold rise (GMFR) for S1 binding IgG antibodies after the second injection | As measured by ELISA | 14 days after the second dose | 
| Geometric mean fold rise (GMFR) for receptor-binding domain (RBD) binding IgG antibodies after the first injection | As measured by ELISA | 21 days after the first dose (on the day of the second dose) | 
| Geometric mean fold rise (GMFR) for receptor-binding domain (RBD) binding IgG antibodies after the second injection | As measured by ELISA | 14 days after the second dose | 
| Geometric mean fold rise (GMFR) for SARS-CoV-2 neutralizing antibodies after the first injection | As measured by ELISA (sVNT) | 21 days after the first dose (on the day of the second dose) | 
| Geometric mean fold rise (GMFR) for SARS-CoV-2 neutralizing antibodies after the second injection | As measured by ELISA (sVNT) | 14 days after the second dose | 
| Change in geometric mean concentration (GMC) for SARS-CoV-2 neutralizing antibodies from baseline to 21 days after the first injection | As measured by ELISA (sVNT) | On the day of the first dose and 21 days after the first dose (on the day of the second dose) | 
| Change in geometric mean concentration (GMC) for SARS-CoV-2 neutralizing antibodies from baseline to 14 days after the second injection | As measured by ELISA (sVNT) | On the day of the first dose and 14 days after the second dose | 
| Change in geometric mean concentration (GMC) for S1 binding IgA antibodies from baseline to 21 days after the first injection | As measured by ELISA | On the day of the first dose and 21 days after the first dose (on the day of the second dose) | 
| Change in geometric mean concentration (GMC) for S1 binding IgA antibodies from baseline to 14 days after the second injection | As measured by ELISA | On the day of the first dose and 14 days after the second dose | 
| Geometric mean fold rise (GMFR) for S1 binding IgA antibodies after the first injection | As measured by ELISA | 21 days after the first dose (on the day of the second dose) | 
| Geometric mean fold rise (GMFR) for S1 binding IgA antibodies after the second injection | As measured by ELISA | 14 days after the second 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 second dose | 
| Change in T-cell proliferation responses from baseline to 21 days after the first injection | Evaluation of CD4+ and CD8+ T-cell proliferation responses as measured by flow cytometry | On the day of the first dose and 21 days after the first dose (on the day of the second dose) | 
| Change in T-cell proliferation responses from baseline to 14 days after the second injection | Evaluation of CD4+ and CD8+ T-cell proliferation responses as measured by flow cytometry | On the day of the first dose and 14 days after the second dose | 
| Change in T-cell IFN-γ secretion from baseline to 21 days after the first injection | As measured by IGRA | On the day of the first dose and 21 days after the first dose (on the day of the second dose) | 
| Change in T-cell IFN-γ secretion from baseline to 14 days after the second injection | As measured by IGRA | On the day of the first dose and 14 days after the second dose | 

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