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

NCT04742842 | Completed Phase 1 DMC

• 1 other identifier: COV101
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 3

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.

Conditions

SARS-CoV2 COVID-19

Outcome Measures

Primary Outcomes (6)

• Frequency of solicited local reactogenicity AEs

  Percentage of participants with any local reaction (pain, swelling/induration, erythema/redness) for 7 days following each vaccination

  Through 7 days after each vaccination (Day 1, 29 for Part A and Day 1 for Part B)

• Frequency of solicited systemic reactogenicity AEs

  Percentage of participants with any systemic reaction (fever, fatigue, chills, myalgia, arthralgia, headache, nausea/vomiting and diarrhea) for 7 days following each vaccination

  Through 7 days after each vaccination (Day 1, 29 for Part A and Day 1 for Part B)

• Frequency of any unsolicited AEs

  Percentage of participants with unsolicited AEs up to Day 57

  Day 1 to Day 57 after the 1st vaccination (Part A) or from Day 1 to Day 29 after booster vaccination (Part B).

• Frequency of any serious adverse events (SAEs)

  Percentage of participants with SAEs from Day 1 to 12 months after 1st vaccination

  Day 1 to 12 months after 1st vaccination

• Frequency of any medically attended adverse events (MAAES)

  Measured by MedDRA classification, severity score and relatedness.

  From Day 1 to 12 months after the 1st vaccination

• Change in safety laboratory values from baseline

  Number of participants with abnormal laboratory values (haematology, chemistry and urinalysis) by FDA toxicity scoring.

  From Day1 to Day 36 in Part A and from Day 1 to Day 8 in Part B

Secondary Outcomes (9)

• 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);

• GMFR from baseline for serum neutralizing antibody response

  At day 57 (Part A) or day 29 (Part B)

• 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

• 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)

• GMFR from baseline for serum S1- and RBD-specific IgG antibody responses

  At day 57 (Part A) and at day 29 (Part B)

Study Arms (5)

Part A: Arm1 (COVIGEN (C19) 0.8 mg ID or Placebo ID)

EXPERIMENTAL

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.

Biological: COVIGEN C19 0.8 mg ID or Placebo ID

Part A: Arm2 (COVIGEN (C19) 2.0 mg IM or Placebo IM)

EXPERIMENTAL

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.

Biological: COVIGEN C19 2.0 mg IM or Placebo IM

Part A; Arm 3 (COVIGEN (C19) 4.0 mg IM or Placebo IM)

EXPERIMENTAL

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

Biological: COVIGEN C19 4.0 mg IM or Placebo IM

Part B: Arm 1 (COVIGEN (C20) 1.0 mg ID) in BNT162b2 primed participants

EXPERIMENTAL

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)

Biological: COVIGEN C20 1.0mg vaccine ID

Part B: Arm 2 (COVIGEN (C20) 1.0 mg ID) in ChAdOx1-S primed participants

EXPERIMENTAL

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)

Biological: COVIGEN C20 1.0mg vaccine ID

Interventions

COVIGEN C19 0.8 mg ID or Placebo ID BIOLOGICAL

2 doses of COVIGEN C19 0.8 mg ID or Placebo ID will be given at Day 1 and Day 29.

Part A: Arm1 (COVIGEN (C19) 0.8 mg ID or Placebo ID)

COVIGEN C19 2.0 mg IM or Placebo IM BIOLOGICAL

2 doses of COVIGEN C19 2.0 mg IM or Placebo IM will be given at Day 1 and Day 29.

Part A: Arm2 (COVIGEN (C19) 2.0 mg IM or Placebo IM)

COVIGEN C19 4.0 mg IM or Placebo IM BIOLOGICAL

2 doses of COVIGEN C19 4.0 mg IM or Placebo IM will be given at Day 1 and Day 29.

Part A; Arm 3 (COVIGEN (C19) 4.0 mg IM or Placebo IM)

COVIGEN C20 1.0mg vaccine ID BIOLOGICAL

COVIGEN C20 1.0mg ID vaccine will be given at Day 1

Part B: Arm 1 (COVIGEN (C20) 1.0 mg ID) in BNT162b2 primed participants; Part B: Arm 2 (COVIGEN (C20) 1.0 mg ID) in ChAdOx1-S primed participants

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and capable of providing written informed consent prior to the performance of any study-specific procedure.
• Male or female, ≥18.0 to ≤75. years of age, at the time of consent.
• The participant must be in good health, as established by pertinent medical history, physical examination and vital signs assessments performed at Screening.
• Body mass index (BMI) of 18 to 40 kg/m2, inclusive, at Screening.
• Women of childbearing potential must have a negative urine pregnancy test at Screening and pre-dose on Day 1, and must agree to remain sexually abstinent, use medically effective contraception (see Section 4.3.10), or have a partner who is sterile or same-sex, from Screening until at least 90 days after the 2nd vaccination (Part A) or the Booster (Part B).
• a. Females with natural amenorrhea for \<2 years (without an alternative medical cause) and who are not surgically sterile, i.e. tubal ligation, bilateral oophorectomy, or complete hysterectomy will only be considered not to be of childbearing potential if they have a documented follicle-stimulating hormone (FSH) value in the postmenopausal range.
• Sexually active male participants who are considered sexually fertile must agree to use either a barrier method of contraception from the time of 1st vaccination until at least 90 days after the 2nd vaccination (Part A) or the Booster (Part B), or have a same sex partner, or have a partner who is permanently sterile or unable to become pregnant;
• Both male and female participants must agree to refrain from sperm and egg donation from the day of the 1st vaccination until at least 90 days after the 2nd vaccination (Part A) or the Booster (Part B)..
• Clinical safety laboratory evaluations at Screening must be toxicity Grade 0 or 1, or deemed not clinically significant by the Investigator.
• The participant must agree to refrain from donating blood or plasma during the study for non-study purposes.
• The participant must agree to have study samples retained for secondary research including exploratory analyses.
• The participant must be able to attend all scheduled visits and to understand and comply with planned study procedures, in the Investigator's judgement.
• Part B only: The participant must have completed a primary course (2 doses) of either Comirnaty (Pfizer BioNTech) or Astra Zeneca vaccine and ≥3 months (≥90 days) has elapsed since receipt of dose 2 in the primary course.

You may not qualify if:

• Female participant who is breastfeeding or intends to become pregnant from Screening until at least 90 days after the 2nd vaccination (Part A) or at least 90 days after booster vaccination (Part B).
• History of any major (per Investigator's discretion) cardiovascular, renal, neurological, metabolic, gastrointestinal, hepato-biliary, uncontrolled hypertension and diabetes, clinically significant chronic pulmonary disease, asthma (with the exception of history of resolved childhood asthma), immunological and autoimmune diseases or any condition which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.
• Chronic use (more than 14 continuous days) of systemic corticosteroids within 30 days prior to Screening. Intra-articular, intra-bursal, or topical (skin or eyes) corticosteroids are permitted.
• History of any haematological malignancy or active neoplastic disease (excluding non-melanoma skin cancer that was successfully treated). Active is defined as having received treatment within the past 5 years.
• History of demyelinating disease or Guillain Barre syndrome.
• Eczema or other significant skin lesion, infection or tattoo at the site of vaccination (left or right upper arm).
• History of blood dyscrasia or significant disorder of coagulation that, in the opinion of the Investigator, contraindicates IM injection (Part A only).
• History of known or suspected hypersensitivity or any severe allergic reaction including anaphylaxis, generalised urticaria, angioedema, and other significant reaction to Kanamycin or any vaccine component,.
• Presence of active viral or bacterial infection, with or without fever (oral temperature ≥37.8 °C) at Screening or within 72 hours prior to each vaccination, if determined by the Investigator to be of clinical significance (enrolment \[provided Screening period does not exceed 30 days\] or dosing may be delayed for full recovery if acceptable to the Investigator).
• Positive serological test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody or HIV (Type 1 or 2) antibody at Screening.
• Known current or previous laboratory confirmed SARS-CoV-2 infection/COVID 19, or positive for SARS-CoV-2 infection, either by SARS CoV 2-specific IgG antibody (Part A only) or RT-PCR, at Screening.
• Suspected SARS-CoV-2 infection/COVID-19, including individuals who are required to self-isolate.
• Individuals currently working in occupations with high risk of exposure to SARS CoV-2, e.g. healthcare workers in direct care of COVID-19 patients, emergency responders or front-line workers.
• Receipt of any other SARS-CoV-2 or other experimental coronavirus vaccine at any time prior to the study or planned receipt of any other SARS-CoV-2 or other experimental vaccine within 57 days of receipt of the 1st study vaccination (Part A only).
• Receipt of any other experimental coronavirus vaccine at any time prior to the study or planned receipt of any other SARS-CoV-2 or other experimental vaccine within 29 days of receipt of the booster vaccination (Part B only).

Sponsors & Collaborators

• University of Sydney: lead
• Bionet Co., Ltd: collaborator
• Technovalia: collaborator
• Telethon Kids Institute: collaborator
• Institute for Clinical Pathology and Medical Research: collaborator

Study Sites (3)

Scientia Clinical Research

Randwick, New South Wales, 2031, Australia

Location

Vaccinology and Immunology Research Trials Unit, Women's and Children's Hospital

Adelaide, South Australia, Australia

Location

Wesfarmers Centre of Vaccines and Infectious Diseases Telethon Kids Institute

Perth, Western Australia, Australia

Location

Study Officials

• Nicholas WOOD, MB BS FRACP PhD.

  University of Sydney

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Non-blind staff preparing and administering vaccine or placebo do not participate in any other aspects of the study. Remaining trial staff and participant are blinded.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: February 8, 2021
• Study Start: June 21, 2021
• Primary Completion: July 30, 2022
• Study Completion: July 30, 2023
• Last Updated: October 30, 2023

Record last verified: 2023-10

Locations

AU (3)