Monovalent Recombinant COVID19 Vaccine (COVAX19)

• ClinicalTrials.gov Identifier: NCT04453852
• Recruitment Status: Recruiting
• First Posted: July 1, 2020
• Last Update Posted: July 1, 2020
• Sponsor: Vaxine Pty Ltd
• Collaborator: Central Adelaide Local Health Network Incorporated
• Information provided by (Responsible Party): Vaxine Pty Ltd

Tracking Information

• First Submitted Date: June 3, 2020
• First Posted Date: July 1, 2020
• Last Update Posted Date: July 1, 2020
• Actual Study Start Date: June 30, 2020
• Estimated Primary Completion Date: July 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 30, 2020)

• Incidence of Adverse Events [ Time Frame: 1 weeks post immunisation ]
  Incidence of Adverse Events 1 week post immunisation
• COVID19 neutralizing antibody titers [ Time Frame: 2 weeks post second immunisation ]
  COVID19 neutralizing antibody titers post immunisation
• COVID19 T cell immunogenicity [ Time Frame: 3 weeks post second immunisation ]
  Frequency of COVID19 spike specific T cells 3 weeks post second immunisation

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: June 30, 2020)

Durability of antibody response [ Time Frame: 6 months post immunisation ]

COVID19 spike specific antibody titers 6 months post second immunisation

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Monovalent Recombinant COVID19 Vaccine
• Official Title: A Randomised, Controlled, Phase 1 Study to Evaluate the Safety and Immunogenicity of a Candidate Adjuvanted Recombinant Protein SARS-COV-2 Vaccine in Healthy Adult Subjects
• Brief Summary: This is a study to test a new vaccine (Covax-19) against COVID-19. COVID-19 is a potentially deadly disease that is caused by a new strain of coronavirus called SARS-CoV-2. To date, SARS-CoV-2 has infected over 4 million people worldwide resulted in the deaths of over three hundred thousand people.

Detailed Description

Human infections with zoonotic coronaviruses including severe acute respiratory syndrome coronavirus (SARS CoV), Middle East respiratory syndrome-associated coronavirus (MERS CoV) and now 2019 SARS-CoV-2, all pose major human public health threats with high case fatality rates. The outbreak of SARS-CoV-2, which shares high similarity with SARS-CoV in its viral genome, has so far caused more than 4,736,000 cases worldwide (as of May 17, 2020) with 3131,545 deaths, resulting in an estimated overall mortality rate of 4-5%. It has a particularly high mortality rate in elderly people and those with chronic disease. To fight the current outbreak and prepare for future human outbreaks of similar coronaviruses, development of a safe and effective SARS-COV-2 vaccine remains a high priority. The fatality rate in the elderly is very high, being 8% for those over 70 and over 20% for those over 80. Notably, over 16% of the Australian population is aged 65 or older. Currently there is no way to control infection with SARS-COV-2 other than minimise exposure by social isolation.

Development of a vaccine against COVID-19 would deliver major public health and economic benefits for Australia, with potential to prevent numerous deaths, particularly among the Australian elderly, reducing the burden on hospital ICUs, helping to alleviate public concern, and ultimately allowing the Australian economy to return as fast as possible to normal.

SARS-CoV and SARS-CoV-2 are both closely related enveloped, single positive-stranded RNA viruses, with one genome encoding a non-structural replicase polyprotein and structural proteins, including spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins. SARS virus neutralizing antibodies were shown to be directed against the S protein. S protein can be cleaved into S1 and S2 subunits by proteases and within the S1 subunit there is a receptor-binding domain (RBD), which was shown to bind angiotensin-converting enzyme 2 (ACE2), which mediates SARS virus entry into cells. SARS-CoV-2 spike protein similarly binds ACE2 for cellular entry. Hence a recombinant SARS-CoV-2 spike protein vaccine that induces neutralising antibody against the virus should be effective against SARS-CoV-2 infection just as seen for SARS CoV.

SARS-COV-2 vaccine design is best informed by previous experience with closely related SARS CoV vaccines. Antibodies against the coronavirus spike protein blocks infection. When recombinant SARS spike protein vaccines produced in insect cells were formulated with Advax adjuvant, this enhances neutralizing antibody and T cell responses which translate into rapid lung viral clearance. Based on experience with developing successful and safe SARS and MERS vaccines, Covax-19 vaccine design is based on recombinant insect cell- expressed SARS-COV-2 spike protein formulated with Advax-SM adjuvant. The vaccine is based on recombinant expression of the ecto-domain of spike protein in insect cells. Insect cell expression of recombinant protein is a well characterised platform, allowing standardised procedures to be rapidly transferred to other facilities around the world. In response to the 2009 H1N1 influenza pandemic, roll-out of a pandemic vaccine based on hemagglutinin protein was extremely fast, with the first cGMP batches of vaccine produced within 6 weeks of virus discovery, and the first human trial subject dosed at Flinders just under 3 months after virus discovery . The use of Advax adjuvant doubled the seroconversion and seroprotection rates while maintaining vaccine tolerability and safety. Recombinant proteins manufactured using this method and formulated with Advax adjuvants have been found to be effective and safe in multiple human trials, including of H1N1/2009 and H5N1 (NCT02335164) and H7N9 (NCT03038776) influenza vaccines.

Covax-19 consists of highly purified recombinant SARS-COV-2 spike protein plus Advax-SM adjuvant in a sterile solution for intramuscular injection. COVAX-19™ vaccine is manufactured using a Sf9 platform. Advax-CpG adjuvant has previously been well tolerated and effective in trials of hepatitis B, H5N1 (NCT02335164) and H7N9 (NCT03038776) influenza vaccines and has recently been tested by the NIH in a US multicentre clinical trial with 2 quadrivalent seasonal influenza vaccines (NCT03945825).

COVAX-19™ vaccine is designed to elicit an immune response against SARS-CoV-2 with generation of neutralising antibodies against its spike protein that prevent the virus attaching to the human ACE2 receptor in the respiratory epithelium. It is also designed to induce T cells against the spike protein.

Study hypotheses

• COVAX-19 vaccine is safe and well tolerated in adult human subjects
• COVAX-19 vaccine will induce durable high titer neutralising antibodies and T cell responses against SARS-COV-2 virus.

• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomised controlled study

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

Non-blind Staff administering vaccine do not participate in any other aspects of the study. Remaining trial staff and participant are blinded

Primary Purpose: Prevention

Condition

• Coronavirus Infection
• COVID

Intervention

• Biological: COVID19 vaccine
  COVID19 recombinant spike protein with Advax-SM adjuvant
  Other Name: COVAX-19 vaccine
• Biological: Saline
  Saline control
  Other Name: Saline control

Study Arms

• Experimental: Group A
  Spike antigen (25ug) + 15 mg Advax-2 adjuvant
  Intervention: Biological: COVID19 vaccine
• Placebo Comparator: Group B
  Saline
  Intervention: Biological: Saline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 30, 2020): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 1, 2021
• Estimated Primary Completion Date: July 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria

• Are males or non-pregnant females, 18 years of age or older.
• Provide written informed consent prior to initiation of any study procedures.
• Are able to understand and comply with planned study procedures and be available for all study visits.
• Are in good health as determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical or psychiatric diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations in the opinion of the Investigator.
• Screening laboratory bloods - White Blood Cells (WBC), Hemoglobin (Hgb), Platelets (PLTs), Alanine Aminotransferase (ALT), Total Bilirubin (T. Bili), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), and Creatinine (Cr)) are within acceptable parameters as determined by the Investigator
• Women of childbearing potential must use an acceptable contraception method and must have a negative urine or serum pregnancy test within 24 hours prior to the first study vaccination.

Exclusion criteria

• Have an acute illness, as determined by the site Principal Investigator (PI) or appropriate sub-investigator, within 72 hours prior to study vaccination.
• Have any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation. *Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial.
• Have immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy.
• Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
• Have known active or recently active (12 months) neoplastic disease or a history of any hematologic malignancy. Non-melanoma, treated, skin cancers are permitted.
• Have known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection.
• Have known hypersensitivity or allergy to insect stings or other components of the study vaccine.
• Have a history of severe reactions following previous immunization with licensed or unlicensed vaccines.
• Have a history of Guillain-Barré Syndrome.
• Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination.
• Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).
• Have a history of alcohol or drug abuse within 5 years prior to study vaccination.
• Have any diagnosis, current or past, of schizophrenia, bipolar disease or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations as determined by the site PI or appropriate sub-investigator.
• Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 5 years prior to study vaccination.
• Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 30 days prior to study vaccination.
• Have taken high-dose inhaled corticosteroids within 30 days prior to study vaccination.
• Have a known history of documented COVID-19 infection within the past 6 months.
• Received an experimental agent within 30 days prior to the study vaccination or expect to receive another experimental agent during the trial-reporting period.
• Female participants who are breastfeeding or plan to breastfeed from the time of the first study vaccination through 30 days after the last study vaccination.
• Any participant whose enrolment, in the opinion of the investigator, would be detrimental to the participant or the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Nikolai Petrovsky, MBBS, Ph.D; +61413131635; nikolai.petrovsky@flinders.edu.au

Contact: David Gordon, MBBS, Ph.D; d.gordon@flinders.edu.au

• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT04453852
• Other Study ID Numbers: 13110
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Vaxine Pty Ltd
• Study Sponsor: Vaxine Pty Ltd
• Collaborators: Central Adelaide Local Health Network Incorporated

Investigators

• Principal Investigator: David Gordon, MBBS, Ph.D; CALHN

• PRS Account: Vaxine Pty Ltd
• Verification Date: June 2020