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

• ClinicalTrials.gov Identifier: NCT04944368
• Recruitment Status: Completed
• First Posted: June 29, 2021
• Last Update Posted: October 13, 2022
• Sponsor: Cinnagen
• Collaborator: Vaxine Pty Ltd
• Information provided by (Responsible Party): Cinnagen

Study Description

Brief Summary:

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:

1. The adjuvanted COVID-19 vaccine candidate is safe and tolerable in adult subjects.
2. The adjuvanted COVID-19 vaccine candidate induces strong immunogenicity against SARS-CoV-2 in adult subjects.

Condition or disease	Intervention/treatment	Phase
Covid19	Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant; Biological: Saline placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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)
• Actual Study Start Date: May 30, 2021
• Actual Primary Completion Date: July 19, 2021
• Actual Study Completion Date: December 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vaccine candidate	Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant; 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; Other Name: SpikoGen
Placebo Comparator: Saline placebo	Biological: Saline placebo; 0.9% sodium chloride (1 mL) injection in two doses with a 21-day interval administered with intramuscular injections in the non-dominant arm; Other Name: Normal saline

Outcome Measures

Primary Outcome Measures :

1. Incidence of solicited adverse events [ Time Frame: For 7 days after each dose ]
   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)
2. Incidence of unsolicited adverse events [ Time Frame: For 28 days after each dose ]
   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)
3. Percentage of participants with seroconversion for S1 binding IgG antibodies after the first injection [ Time Frame: 21 days after the first dose (on the day of the second dose) ]
   As measured by ELISA
4. Percentage of participants with seroconversion for S1 binding IgG antibodies after the second injection [ Time Frame: 14 days after the second dose ]
   As measured by ELISA
5. Change in geometric mean concentration (GMC) for S1 binding IgG antibodies from baseline to 21 days after the first injection [ Time Frame: On the day of the first dose and 21 days after the first dose (on the day of the second dose) ]
   As measured by ELISA
6. Change in geometric mean concentration (GMC) for S1 binding IgG antibodies from baseline to 14 days after the second injection [ Time Frame: On the day of the first dose and 14 days after the second dose ]
   As measured by ELISA

Secondary Outcome Measures :

1. Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies after the first injection [ Time Frame: 21 days after the first dose (on the day of the second dose) ]
   As measured by ELISA (sVNT)
2. Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies after the first injection [ Time Frame: 21 days after the first dose (on the day of the second dose) ]
   As measured by cVNT
3. Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies after the second injection [ Time Frame: 14 days after the second dose ]
   As measured by ELISA (sVNT)
4. Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies after the second injection [ Time Frame: 14 days after the second dose ]
   As measured by cVNT
5. Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgA antibodies after the first injection [ Time Frame: 21 days after the first dose (on the day of the second dose) ]
   As measured by ELISA
6. Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgA antibodies after the second injection [ Time Frame: 14 days after the second dose ]
   As measured by ELISA
7. Percentage of participants with seroconversion for S1 binding IgA antibodies after the first injection [ Time Frame: 21 days after the first dose (on the day of the second dose) ]
   As measured by ELISA
8. Percentage of participants with seroconversion for S1 binding IgA antibodies after the second injection [ Time Frame: 14 days after the second dose ]
   As measured by ELISA
9. Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgG antibodies after the first injection [ Time Frame: 21 days after the first dose (on the day of the second dose) ]
   As measured by ELISA
10. Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgG antibodies after the second injection [ Time Frame: 14 days after the second dose ]
    As measured by ELISA
11. Change in geometric mean concentration (GMC) for receptor-binding domain (RBD) binding IgG antibodies from baseline to 21 days after the first injection [ Time Frame: On the day of the first dose and 21 days after the first dose (on the day of the second dose) ]
    As measured by ELISA
12. Change in geometric mean concentration (GMC) for receptor-binding domain (RBD) binding IgG antibodies from baseline to 14 days after the second injection [ Time Frame: On the day of the first dose and 14 days after the second dose ]
    As measured by ELISA
13. Geometric mean fold rise (GMFR) for S1 binding IgG antibodies after the first injection [ Time Frame: 21 days after the first dose (on the day of the second dose) ]
    As measured by ELISA
14. Geometric mean fold rise (GMFR) for S1 binding IgG antibodies after the second injection [ Time Frame: 14 days after the second dose ]
    As measured by ELISA
15. Geometric mean fold rise (GMFR) for receptor-binding domain (RBD) binding IgG antibodies after the first injection [ Time Frame: 21 days after the first dose (on the day of the second dose) ]
    As measured by ELISA
16. Geometric mean fold rise (GMFR) for receptor-binding domain (RBD) binding IgG antibodies after the second injection [ Time Frame: 14 days after the second dose ]
    As measured by ELISA
17. Geometric mean fold rise (GMFR) for SARS-CoV-2 neutralizing antibodies after the first injection [ Time Frame: 21 days after the first dose (on the day of the second dose) ]
    As measured by ELISA (sVNT)
18. Geometric mean fold rise (GMFR) for SARS-CoV-2 neutralizing antibodies after the second injection [ Time Frame: 14 days after the second dose ]
    As measured by ELISA (sVNT)
19. Change in geometric mean concentration (GMC) for SARS-CoV-2 neutralizing antibodies from baseline to 21 days after the first injection [ Time Frame: On the day of the first dose and 21 days after the first dose (on the day of the second dose) ]
    As measured by ELISA (sVNT)
20. Change in geometric mean concentration (GMC) for SARS-CoV-2 neutralizing antibodies from baseline to 14 days after the second injection [ Time Frame: On the day of the first dose and 14 days after the second dose ]
    As measured by ELISA (sVNT)
21. Change in geometric mean concentration (GMC) for S1 binding IgA antibodies from baseline to 21 days after the first injection [ Time Frame: On the day of the first dose and 21 days after the first dose (on the day of the second dose) ]
    As measured by ELISA
22. Change in geometric mean concentration (GMC) for S1 binding IgA antibodies from baseline to 14 days after the second injection [ Time Frame: On the day of the first dose and 14 days after the second dose ]
    As measured by ELISA
23. Geometric mean fold rise (GMFR) for S1 binding IgA antibodies after the first injection [ Time Frame: 21 days after the first dose (on the day of the second dose) ]
    As measured by ELISA
24. Geometric mean fold rise (GMFR) for S1 binding IgA antibodies after the second injection [ Time Frame: 14 days after the second dose ]
    As measured by ELISA
25. Incidence of serious adverse events (SAEs) and suspected unexpected serious adverse reaction (SUSARs) [ Time Frame: For 6 months after the second dose ]
    As defined using system organ classes and preferred terms of the Medical Dictionary for Regulatory Activities (MedDRA)
26. Change in T-cell proliferation responses from baseline to 21 days after the first injection [ Time Frame: On the day of the first dose and 21 days after the first dose (on the day of the second dose) ]
    Evaluation of CD4+ and CD8+ T-cell proliferation responses as measured by flow cytometry
27. Change in T-cell proliferation responses from baseline to 14 days after the second injection [ Time Frame: On the day of the first dose and 14 days after the second dose ]
    Evaluation of CD4+ and CD8+ T-cell proliferation responses as measured by flow cytometry
28. Change in T-cell IFN-γ secretion from baseline to 21 days after the first injection [ Time Frame: On the day of the first dose and 21 days after the first dose (on the day of the second dose) ]
    As measured by IGRA
29. Change in T-cell IFN-γ secretion from baseline to 14 days after the second injection [ Time Frame: On the day of the first dose and 14 days after the second dose ]
    As measured by IGRA

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Iran, Islamic Republic of

Espinas Palace Hotel

Tehran, Iran, Islamic Republic of, 1981846911

Sponsors and Collaborators

Cinnagen

Vaxine Pty Ltd

Investigators

• Principal Investigator: Payam Tabarsi, M.D.; Shahid Beheshti University of Medical Sciences

More Information

Publications of Results:

Tabarsi P, Anjidani N, Shahpari R, Mardani M, Sabzvari A, Yazdani B, Roshanzamir K, Bayatani B, Taheri A, Petrovsky N, Li L, Barati S. Safety and immunogenicity of SpikoGen(R), an Advax-CpG55.2-adjuvanted SARS-CoV-2 spike protein vaccine: a phase 2 randomized placebo-controlled trial in both seropositive and seronegative populations. Clin Microbiol Infect. 2022 Sep;28(9):1263-1271. doi: 10.1016/j.cmi.2022.04.004. Epub 2022 Apr 15.

• Responsible Party: Cinnagen
• ClinicalTrials.gov Identifier: NCT04944368
• Other Study ID Numbers: VAC.CIN.PT.II; IRCT20150303021315N23 ( Registry Identifier: Iranian Registry of Clinical Trials )
• First Posted: June 29, 2021
• Last Update Posted: October 13, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cinnagen:

COVID-19; SARS-COV-2; Recombinant protein; Spike; Advax-SM; Advax; Vaccine; Adjuvant

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Myeloma Proteins; Paraproteins; Immunologic Factors; Physiological Effects of Drugs