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

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)

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:

1. A booster dose of the SpikoGen COVID-19 vaccine is safe and tolerable in adult subjects.
2. A booster dose of the SpikoGen COVID-19 vaccine induces strong immunogenicity against SARS-CoV-2 in adult subjects.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant; Biological: Saline placebo

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Orchid Life Department, Orchid Pharmed Company

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
• 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.

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
Experimental: SpikoGen COVID-19 Vaccine	Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant; 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; Other Names: COVAX-19
Placebo Comparator: Saline Placebo	Biological: Saline placebo; 0.9% sodium chloride (1 mL); a single intramuscular injection into the deltoid muscle of the non-dominant arm

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cinnagen
• Collaborators: Vaxine Pty Ltd

Publications and helpful links

General Publications

• Tabarsi P, Anjidani N, Shahpari R, Roshanzamir K, Fallah N, Andre G, Petrovsky N, Barati S. Immunogenicity and safety of SpikoGen(R), an adjuvanted recombinant SARS-CoV-2 spike protein vaccine as a homologous and heterologous booster vaccination: A randomized placebo-controlled trial. Immunology. 2022 Nov;167(3):340-353. doi: 10.1111/imm.13540. Epub 2022 Jul 13.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2021
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): June 20, 2022

Study Registration Dates

• First Submitted: January 3, 2022
• First Submitted That Met QC Criteria: January 3, 2022
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Actual): October 14, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Vaccine; COVID-19; Advax; Adjuvant; 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.BOOSTER; IRCT20150303021315N26 (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