The Safety and Immunogenicity of a DNA-based Vaccine (COVIGEN) in Healthy Volunteers

Phase 1

Completed

• Conditions: SARS-CoV2 COVID-19
• Interventions: Biological: COVIGEN C19 2.0 mg IM or Placebo IM; Biological: COVIGEN C20 1.0mg vaccine ID; Biological: COVIGEN C19 0.8 mg ID or Placebo ID; Biological: COVIGEN C19 4.0 mg IM or Placebo IM

• Registration Number: NCT04742842
• Lead Sponsor: University of Sydney

Brief Summary

In this trial, we are evaluating the safety and tolerability of a new investigational DNA vaccine to protect against SARS CoV-2 virus, called COVIGEN, that is developed by a company called BioNet-Asia.

A device will be used to inject the vaccine that does not require the use of a needle (needle-free injection made by a company called Pharmajet). For delivery into the skin (intradermally) a device called "Tropis" will be used, and for delivery into the muscle (intramuscularly) a device called "Stratis" will be used.

This is a 2 part study

In Part A vaccine naive participants will be given 2 vaccinations, either two active vaccines or two placebo vaccines on Day 1 and Day 29. COVIGEN C19 vaccine will be used in Part A

In Part B participants who have previously received a 2-dose primary COVID vaccine schedule will be given a booster dose of active vaccine. COVIGEN C20 vaccine will be used in Part B.

Participants in part A and B will be followed up using a combination of on-site and telephone visits for assessment of safety and immunogenicity for 12 months from 1st vaccination.

Detailed Description

Part A Vaccine Naïve participants: The study comprises three dose groups (0.8 mg COVIGEN, administered ID, 2 mg COVIGEN, administered IM and 4 mg COVIGEN, administered IM) with 50 participants in each group. Each group of 50 participants comprises two sub-groups: 25 young adults and 25 older adults. Within each group and within each sub-group, participants will be randomised 4:1 to receive COVIGEN or placebo in a double-blind fashion.

Participants will receive 2 study vaccinations, 28 days apart (Day 1 and Day 29). Each dose will be divided into 2 injections, with each injection being administered using a needle free injection system into the upper arm (left and right) at each visit.

The study will utilise a sequential dose-escalating design with a 48-hour observation period required for sentinel participants prior to the decision to dose escalate. Enrolment of the remainder of each age cohort will commence at least 48 hours after the last of the sentinel participants has received a vaccine. A Safety Review Committee (SRC) will supervise enrolment and monitoring of participant safety throughout the trial

Part B: Vaccine booster participants: The study comprises a single dose group (1.0mg COVIGEN, administered ID) to 50 participants in total, comprising 25 participants who have received a primary course of 2 doses of Pfizer BioNTech vaccine and 25 participants who have received a primary course of 2 doses of Astra Zeneca vaccine.

The dose will be divided into 2 injections, with each injection being administered using a needle free injection system into the upper arm (left and right) at each visit.

Participants will be followed up using a combination of on-site and telephone visits for assessment of safety and immunogenicity for 12 months from 1st vaccination.

Study Timeline

• Study First Submitted: 2021-01-28
• Study First Submitted QC: 2021-02-03
• Study First Posted: 2021-02-08
• Study Start: 2021-06-21
• Primary Completion: 2022-07-30
• Study Completion: 2023-07-30
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-27
• Last Update Posted: 2023-10-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A: Arm2 (COVIGEN (C19) 2.0 mg IM or Placebo IM)	COVIGEN C19 2.0 mg IM or Placebo IM	Participants will be randomized to receive either COVIGEN C19 (2 mg) given by IM (n=40) or saline placebo (n=10), administered in a two dose regimen, 28 days apart.
Part B: Arm 1 (COVIGEN (C20) 1.0 mg ID) in BNT162b2 primed participants	COVIGEN C20 1.0mg vaccine ID	Participants in Part B who have received a 2 dose primary course of Pfizer BNT162b2 vaccine will receive COVIGEN C20 (1mg) vaccine given by ID (n=25)
Part B: Arm 2 (COVIGEN (C20) 1.0 mg ID) in ChAdOx1-S primed participants	COVIGEN C20 1.0mg vaccine ID	Participants in Part B who have received a 2 dose primary course of Astra Zeneca ChAdOx1-S vaccine will receive COVIGEN C20 (1mg) vaccine given by ID (n=25)
Part A: Arm1 (COVIGEN (C19) 0.8 mg ID or Placebo ID)	COVIGEN C19 0.8 mg ID or Placebo ID	Participants will be randomized to receive either COVIGEN C19 (0.8 mg) given by ID (n=40) or saline placebo (n=10), administered in a two dose regimen, 28 days apart.
Part A; Arm 3 (COVIGEN (C19) 4.0 mg IM or Placebo IM)	COVIGEN C19 4.0 mg IM or Placebo IM	Participants will be randomized to receive either COVIGEN C19 (4 mg) given by IM (n=40) or saline placebo (n=10), administered in a two dose regimen, 28 days apart

Primary Outcome Measures

Name	Time	Method
Frequency of solicited local reactogenicity AEs	Through 7 days after each vaccination (Day 1, 29 for Part A and Day 1 for Part B)	Percentage of participants with any local reaction (pain, swelling/induration, erythema/redness) for 7 days following each vaccination
Frequency of solicited systemic reactogenicity AEs	Through 7 days after each vaccination (Day 1, 29 for Part A and Day 1 for Part B)	Percentage of participants with any systemic reaction (fever, fatigue, chills, myalgia, arthralgia, headache, nausea/vomiting and diarrhea) for 7 days following each vaccination
Frequency of any unsolicited AEs	Day 1 to Day 57 after the 1st vaccination (Part A) or from Day 1 to Day 29 after booster vaccination (Part B).	Percentage of participants with unsolicited AEs up to Day 57
Frequency of any serious adverse events (SAEs)	Day 1 to 12 months after 1st vaccination	Percentage of participants with SAEs from Day 1 to 12 months after 1st vaccination
Frequency of any medically attended adverse events (MAAES)	From Day 1 to 12 months after the 1st vaccination	Measured by MedDRA classification, severity score and relatedness.
Change in safety laboratory values from baseline	From Day1 to Day 36 in Part A and from Day 1 to Day 8 in Part B	Number of participants with abnormal laboratory values (haematology, chemistry and urinalysis) by FDA toxicity scoring.

Secondary Outcome Measures

Name	Time	Method
GMFR from baseline for serum S1- and RBD-specific IgG antibody responses	At day 57 (Part A) and at day 29 (Part B)	As measured by ELISA
GMFR from baseline for serum neutralizing antibody response	At day 57 (Part A) or day 29 (Part B)	Measured by SARS-CoV-2 Neutralization assay
Geometric means of T-cells (spot-forming cells) producing IFNγ, IL-2, or both for S protein specific IFN-γ and IL-2 T-cell responses	At day 1, day 29, and day 57 (Part A) or at Day 1, Day 8, and Day 29 (Part B only)	SARS-CoV-2 Spike Protein dual IFN-γ and IL-2 T-cell ELISpot (FluoroSpot)
Proportion of participants with significant T-cell responses for S protein specific IFN-γ and IL-2 T-cell responses	At day 57 for Part A and at day 29 for Part B	IL-2 T-cell ELISpot (FluoroSpot)
GMTs for serum neutralizing antibody response	At day1, day 29 and day 57 (Part A) and Day 1, Day 8, Day 29 (Part B only);	Level of neutralizing antibodies as measured by SARS-CoV-2 Neutralization assay
Seroconversion rate for serum neutralizing antibody response	At day 57 compare to baseline for Part A and at day 29 compare to baseline for Part B	Defined as proportion of participants with a with a ≥4-fold rise
GMTs for serum S1- and RBD-specific IgG antibody responses	At day 1, day 29 and day 57 (Part A) and at Day 1, Day 8, Day 29; (Part B only)	SARS-CoV-2 anti-S1 and anti-RBD IgG antibody ELISAs
Seroconversion rate serum S1- and RBD-specific IgG antibody responses	At day 57 compare to baseline for Part A and at day 29 compare to baseline for Part B	Defined as the proportion of participants with a ≥ 4-fold rise
Fold rise of T-cells (spot-forming cells) producing IFNγ, IL-2, or both for S protein specific IFN-γ and IL-2 T-cell responses	At day 57 compared to baseline for Part A and at day 29 compare to baseline for Part B	SARS-CoV-2 Spike Protein dual IFN-γ and IL-2 T-cell ELISpot (FluoroSpot)

Trial Locations

Locations (3)

Vaccinology and Immunology Research Trials Unit, Women's and Children's Hospital; 🇦🇺 Adelaide, South Australia, Australia

Scientia Clinical Research; 🇦🇺 Randwick, New South Wales, Australia

Wesfarmers Centre of Vaccines and Infectious Diseases Telethon Kids Institute; 🇦🇺 Perth, Western Australia, Australia