Safety and Immune Response of Adjuvanted SARS-CoV-2 (COVID-19) Beta Variant RBD Recombinant Protein (DoCo-Pro-RBD-1 + MF59®) and mRNA (MIPSCo-mRNA-RBD-1) Vaccines in Healthy Adults

NCT05272605 | Completed Phase 1 DMC

• 1 other identifier: UoM-SARS-CoV-2-01
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 2

Brief Summary

This is a study of two experimental SARS-CoV-2 vaccines against the virus called SARS-CoV-2 virus. The first of the experimental vaccines is called DoCo-Pro-RBD-1 + M59® and contains a laboratory made protein which looks the same as a protein in the SARS-CoV-2 virus. As this protein is so similar to a protein in the SARS-CoV-2 virus, it allows the immune system to develop immunity against the real virus by producing specific antibodies against this protein. Antibodies are substances in the blood which could help protect against future infection. The second of the experimental vaccines that will be tested is called MIPSCo-mRNA-RBD-1. This type of vaccine uses messenger ribonucleic acid (mRNA) which is a set of instructions for a cell to make a viral protein called an antigen. Antigens are substances that can trigger the body's defences to produce antibodies that fight against the disease. This study will test these two experimental COVID-19 vaccines in people who have previously received two doses of ComirnatyTM (Pfizer Australia Pty Ltd) or VaxzevriaTM (AstraZeneca Pty Ltd) and a third booster vaccination with either ComirnatyTM or SpikevaxTM (Moderna). This study is the first time this recombinant protein vaccine and this mRNA vaccine will be given to humans. The purpose of this study is to determine what amount, or dose, of the experimental vaccines is safe and produces the desired immune response and antibody level for future investigations. It will do this by testing 3 different dose levels for each of the two vaccines. Each participant will receive a single vaccine at one of the three dose levels, or a placebo injection. This study is the first time this recombinant protein vaccine and this mRNA vaccine will be given to humans.

Conditions

SARS-CoV-2

Keywords

COVID-19

Outcome Measures

Primary Outcomes (5)

• Serious adverse events (SAEs), medically attended adverse events (MAAEs) and any adverse events (AEs) leading to study withdrawal at any time during the study.

  Frequency

  Through to study completion at Day 181.

• SAEs post vaccination.

  Frequency

  Day 1 to 29 (28 Days post vaccination).

• Solicited local and systemic reactogenicity AEs post vaccination.

  Frequency, severity, duration and peak intensity

  Within 7 days after vaccination (Day 1)

• Unsolicited AEs post vaccination.

  Frequency

  Day 1 to Day 29 (28 days post vaccination).

• Percentage of participants who achieve a boost response post vaccination.

  Defined as a 4-fold increase in SARS-CoV-2 neutralising or RBD-specific Ab titres from baseline.

  28 days after vaccination

Secondary Outcomes (5)

• MAAEs from Day 1 to 6 months after vaccination.

  6 months after vaccination.

• The number of participants that develop an antibody response at least 4 times higher than baseline antibody titers.

  At baseline (Day 1), Day 29 (28 days after vaccination), and 3, and 6 months after vaccination

• Number of participants that mount a T cell response for SARS-CoV-2 RBD-derived peptide antigens.

  Baseline (Day 1), Day 8 (7 days after vaccination), Day 29 (28 days after vaccination) and 3 and 6 months after vaccination.

• Number of participants that mount a T cell response that leads to type-1 cytokines (such as Interferon-gamma) versus type-2 cytokines (such as Interleukin 4, 5 and 13).

  Baseline (Day 1), Day 8 (7 days after vaccination), Day 29 (28 days after vaccination) and 3 and 6 months after vaccination.

• The ratio of T cell derived type 1 versus type 2 cytokines in participants that mount a T cell response.

  Baseline (Day 1), Day 8 (7 days after vaccination), Day 29 (28 days after vaccination) and 3 and 6 months after vaccination.

Study Arms (7)

Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1) 5mcg + MF59

EXPERIMENTAL

DoCo-Pro-RBD-1 antigen 5mcg mixed with MF59 adjuvant in 0.5 mL suspension, administered intramuscularly in a one dose regimen, on Day 1

Biological: Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59)

Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1)15mcg + MF59

EXPERIMENTAL

DoCo-Pro-RBD-1 antigen 15mcg mixed with MF59 adjuvant in 0.5 mL suspension, administered intramuscularly in a one dose regimen, on Day 1

Biological: Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59)

Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1) 45mcg + MF59

EXPERIMENTAL

DoCo-Pro-RBD-1 antigen 45mcg mixed with MF59 adjuvant in 0.5 mL suspension, administered intramuscularly in a one dose regimen, on Day 1

Biological: Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59)

SARS-CoV-2 beta variant RBD mRNA vaccine (MIPSCo-mRNA-RBD-1) 10mcg

EXPERIMENTAL

MIPSCo-mRNA-RBD-1 antigen 10mcg administered intramuscularly as a 0.5 mL dose in a one dose regimen on Day 1

Biological: SARS-CoV-2 beta variant RBD mRNA vaccine

SARS-CoV-2 beta variant RBD mRNA vaccine (MIPSCo-mRNA-RBD-1) 20mcg

EXPERIMENTAL

MIPSCo-mRNA-RBD-1 antigen 20mcg administered intramuscularly as a 0.5 mL dose in a one dose regimen on Day 1

Biological: SARS-CoV-2 beta variant RBD mRNA vaccine

SARS-CoV-2 beta variant RBD mRNA vaccine (MIPSCo-mRNA-RBD-1) 50mcg

EXPERIMENTAL

MIPSCo-mRNA-RBD-1 antigen 50mcg administered intramuscularly as a 0.5 mL dose in a one dose regimen on Day 1

Biological: SARS-CoV-2 beta variant RBD mRNA vaccine

Normal saline (0.9%)

PLACEBO COMPARATOR

Normal saline (0.9%) administered intramuscularly as a 0.5 mL dose in a one dose regimen on Day 1

Other: Normal Saline

Interventions

Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59) BIOLOGICAL

Single booster dose in healthy adults previously vaccinated with two doses of CominartyTM (BNT162b2 \[mRNA\]) or VaxzevriaTM (ChAdOx1-S) COVID-19 and a third booster dose of either ComirnatyTM or SpikevaxTM vaccines.

Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1) 45mcg + MF59; Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1) 5mcg + MF59; Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1)15mcg + MF59

SARS-CoV-2 beta variant RBD mRNA vaccine BIOLOGICAL

Single booster dose in healthy adults previously vaccinated with two doses of CominartyTM (BNT162b2 \[mRNA\]) or VaxzevriaTM (ChAdOx1-S) COVID-19 and a third booster dose of either ComirnatyTM or SpikevaxTM vaccines.

SARS-CoV-2 beta variant RBD mRNA vaccine (MIPSCo-mRNA-RBD-1) 10mcg; SARS-CoV-2 beta variant RBD mRNA vaccine (MIPSCo-mRNA-RBD-1) 20mcg; SARS-CoV-2 beta variant RBD mRNA vaccine (MIPSCo-mRNA-RBD-1) 50mcg

Normal Saline OTHER

Placebo comparator

Normal saline (0.9%)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults 18 to 64 years of age, inclusive at screening previously vaccinated with a 2-dose schedule of Cominarty™ or Vaxzevria™.
• ≥ 3 months (90 days) since receipt of a booster dose of either ComirnatyTM or SpikevaxTM.
• Be in good health as determined by medical history, physical examination, vital signs, and clinical laboratory assessments with no clinically significant abnormalities as judged by the Investigator at screening and randomisation. Vital signs must be within medically acceptable ranges prior to the first vaccination.
• Participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile \[ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy\] or postmenopausal \[defined as amenorrhea of at least 12 consecutive months\]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through the end of the study OR agree to consistently use a medically acceptable method of contraception listed below from at least 28 days prior to enrollment and through the end of the study:
• a. Condoms (male or female); Diaphragm; Cervical cap; Intrauterine device; Oral or patch contraceptives; Norplant®, Depo-Provera®, or another regulatory approved contraceptive method; Abstinence, as a form of contraception, is acceptable if in line with the participant's lifestyle.
• NOTE: Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, post- ovulation methods) and withdrawal method (coitus interruptus) are not acceptable forms of contraception.
• Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study.
• Willing and able to give informed consent prior to study enrollment and to comply with all study procedures.

You may not qualify if:

• Potential study participants will be excluded from the study if ANY of the following criteria apply:
• History of test-confirmed (by PCR, rapid antigen test (RAT) to SARS-CoV-2) COVID-19 infection within 3 months (90 days) prior to randomisation.
• Participants with a BMI \> 35kg/m2.
• Positive result for rheumatoid factor (RF) at Screening.
• Positive test at Screening for human immunodeficiency virus (Types 1 or 2) antibody, hepatitis B surface antigen or hepatitis C virus antibody.
• Clinical laboratory test results not within normal range and judged to be clinically relevant abnormalities by the investigator.
• History of prior cardiac inflammatory disease (endocarditis, myocarditis or pericarditis).
• History of demyelinating disease or Guillain Barré syndrome.
• Fever (non-axillary temperature \>37.5°C) or any other symptoms of infection that have not completely resolved within 3 days prior to Randomisation (Day 1).
• Presence of current active viral infection or bacterial infection, at Screening or Randomisation (Day 1), which is determined by the Investigator to be of clinical significance.
• Participation in research involving receipt of an investigational product (drug/biologic/device) within 90 days prior to the first study vaccination or an intention to participate in another clinical trial at any time during the conduct of this study.
• Received any other vaccine within 30 days prior to the first study vaccination, other than licensed influenza vaccine, which can be administered up to 14 days prior to randomization.
• Any known allergies to products contained in the investigational products.
• Any history of anaphylaxis to any prior vaccine, food, drug, toxin or other exposure.
• Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.

Sponsors & Collaborators

• University of Melbourne: lead
• Southern Star Research: collaborator

Study Sites (2)

Vaccine and Immunisation Research Group, Doherty Institute, University of Melbourne

Melbourne, Victoria, 3010, Australia

Location

Royal Melbourne Hospital, Victorian Infectious Diseases Service (VIDS)

Melbourne, Victoria, 3052, Australia

Location

Related Publications (1)

• Nolan TM, Deliyannis G, Griffith M, Braat S, Allen LF, Audsley J, Chung AW, Ciula M, Gherardin NA, Giles ML, Gordon TP, Grimley SL, Horng L, Jackson DC, Juno JA, Kedzierska K, Kent SJ, Lewin SR, Littlejohn M, McQuilten HA, Mordant FL, Nguyen THO, Soo VP, Price B, Purcell DFJ, Ramanathan P, Redmond SJ, Rockman S, Ruan Z, Sasadeusz J, Simpson JA, Subbarao K, Fabb SA, Payne TJ, Takanashi A, Tan CW, Torresi J, Wang JJ, Wang LF, Al-Wassiti H, Wong CY, Zaloumis S, Pouton CW, Godfrey DI. Interim results from a phase I randomized, placebo-controlled trial of novel SARS-CoV-2 beta variant receptor-binding domain recombinant protein and mRNA vaccines as a 4th dose booster. EBioMedicine. 2023 Dec;98:104878. doi: 10.1016/j.ebiom.2023.104878. Epub 2023 Nov 27.

  PMID: 38016322 DERIVED

Related Links

• Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine

MeSH Terms

Conditions

COVID-19

Interventions

MF59 oil emulsion; Saline Solution

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Prof. Terry Nolan

  Peter Doherty Institute for Infection and Immunity, The University of Melbourne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2022
• First Posted: March 9, 2022
• Study Start: April 5, 2022
• Primary Completion: April 19, 2023
• Study Completion: April 19, 2023
• Last Updated: May 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)