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

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)

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant; Biological: Saline placebo

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Phase 2

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1981846911
    • Espinas Palace Hotel

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Normal saline
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 Names: SpikoGen

What is the study measuring?

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
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
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
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

Collaborators and Investigators

• Sponsor: Cinnagen
• Collaborators: Vaxine Pty Ltd

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2021
• Primary Completion (Actual): July 19, 2021
• Study Completion (Actual): December 30, 2021

Study Registration Dates

• First Submitted: June 19, 2021
• First Submitted That Met QC Criteria: June 28, 2021
• First Posted (Actual): June 29, 2021

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Vaccine; COVID-19; Advax; Adjuvant; SARS-COV-2; Spike; Recombinant protein; Advax-SM
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Myeloma Proteins; Paraproteins
• Other Study ID Numbers: VAC.CIN.PT.II; IRCT20150303021315N23 (Registry Identifier: Iranian Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No