Safety, Tolerability, and Immunogenicity of Trivalent Coronavirus Vaccine Candidate VBI-2901e With E6020 Adjuvant

NCT05614245 | Withdrawn Phase 1 DMC

• 1 other identifier: VBI-2901e-CT01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

VBI-2901e is an investigational vaccine candidate that uses enveloped virus-like particles (eVLPs) to express the spike proteins of three coronaviruses: SARS-CoV-2 (the virus that causes COVID-19 disease), SARS-CoV-1 and MERS-CoV. The trivalent vaccine candidate is designed to induce neutralizing antibody and cell-mediated immune responses against the spike protein of the original strain of SARS-CoV-2 coronavirus, variants and subvariants of SARS-CoV-2 (such as Beta, Delta and Omicron BA.5) and other related coronaviruses that could emerge in the future. VBI-2901e contains two adjuvants: aluminum phosphate and E6020. The role of the adjuvants is to create a stronger immune response to the vaccine. This Phase 1 study will be an open-label study of VBI-2901e comparing three dose levels of the E6020 adjuvant component (1, 3, or 10 µg per dose) in adults 18 to 40 years of age who had previously received two or more vaccinations with licensed COVID-19 vaccine(s). VBI-2901e at each dose level of E6020 will be administered as either a single dose or two-dose regimen. The purpose of the study is to test the safety of VBI-2901e and to learn more about its ability to boost immune responses against SARS-CoV-2 and the two related coronaviruses SARS-CoV-1 and MERS-CoV.

Conditions

COVID-19; Coronavirus Infections

Keywords

COVID-19; SARS-CoV-2; SARS-CoV-1; MERS-CoV; vaccine; enveloped virus-like particle (eVLP); coronavirus; adjuvant; E6020

Outcome Measures

Primary Outcomes (6)

• Local reactions (solicited adverse events) within 7 days of study vaccination

  Through 7 days after each vaccination

• Systemic reactions (solicited adverse events) within 7 days of study vaccination

  Through 7 days after each vaccination

• Unsolicited adverse events within 28 days of study vaccination

  Through 28 days after each vaccination

• Serious adverse events within 28 days of study vaccination and end of study

  Through end of study (approximately 1 year)

• Medically-attended adverse events within 28 days of study vaccination and end of study

  Through end of study (approximately 1 year)

• Seroresponse rate against SARS-CoV-2 ancestral (Wuhan) strain

  Study days 1, 28 and 56

Secondary Outcomes (8)

• Seroresponse rate against SARS-CoV-2 variants of concern (Beta, Delta and Omicron)

  Study days 1, 28 and 56

• Seroresponse rate against SARS-CoV-1 and MERS-CoV

  Study days 1, 28 and 56

• Geometric mean titer (GMT) of SARS-CoV-2 neutralizing antibodies

  Study days 1, 7, 28, 35, 56, 84, 168 and 336

• Geometric mean fold rise (GMFR) in serum neutralizing antibody titer against SARS-CoV-2 ancestral (Wuhan) strain and variants of concern (Beta, Delta and Omicron), SARS-CoV-1 and MERS-CoV

  Study days 1, 7, 28, 35, 56, 84, 168 and 336

• GMT of serum IgG antibody to spike protein and receptor-binding-domain (RBD) against SARS-CoV-2 ancestral (Wuhan) strain, selected SARS-CoV-2 variants (Beta, Delta and Omicron), SARS-CoV-1 and MERS-CoV

  Study days 1, 7, 28, 35, 56, 84, 168, and 336

Other Outcomes (1)

• GMT of neutralizing antibodies against potentially zoonotic beta-coronaviruses

  Study days 1, 7, 28, 35, 56, 84, 168 and 336

Study Arms (6)

Group G1, Subgroup G1-A

EXPERIMENTAL

10 participants aged 18-40 years to receive one dose of VBI-2901e at 5 µg spike protein and 1 µg E6020 per dose at Day 1

Biological: VBI-2901e

Group G1, Subgroup G1-B

EXPERIMENTAL

10 participants aged 18-40 years to receive two doses of VBI-901e at 5 µg spike protein and 1 µg E6020 per dose at Day 1 and Day 28

Biological: VBI-2901e

Group G2, Subgroup G2-A

EXPERIMENTAL

10 participants aged 18-40 years to receive one dose of VBI-2901e at 5 µg spike protein and 3 µg E6020 per dose at Day 1

Biological: VBI-2901e

Group G2, Subgroup G2-B

EXPERIMENTAL

10 participants aged 18-40 years to receive two doses of VBI-901e at 5 µg spike protein and 3 µg E6020 per dose at Day 1 and Day 28

Biological: VBI-2901e

Group G3, Subgroup G3-A

EXPERIMENTAL

10 participants aged 18-40 years to receive one dose of VBI-2901e at 5 µg spike protein and 10 µg E6020 per dose at Day 1

Biological: VBI-2901e

Group G3, Subgroup G3-B

EXPERIMENTAL

10 participants aged 18-40 years to receive two doses of VBI-901e at 5 µg spike protein and 10 µg E6020 per dose at Day 1 and Day 28

Biological: VBI-2901e

Interventions

VBI-2901e BIOLOGICAL

Intramuscular injection of VBI-2901e, an investigational trivalent coronavirus vaccine that contains three coronavirus spike proteins with aluminum phosphate and E6020 adjuvants

Group G1, Subgroup G1-A; Group G1, Subgroup G1-B; Group G2, Subgroup G2-A; Group G2, Subgroup G2-B; Group G3, Subgroup G3-A; Group G3, Subgroup G3-B

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subject 18-40 years of age
• Be willing and able to provide personally signed informed consent indicating understanding of the purpose, procedures required for the study and potential risks and benefits of the study, and be willing to participate in the study
• Healthy participants with no chronic medical conditions at study enrollment and during the 6 months before enrollment. Participants with history of asymptomatic SARS-CoV-2 infection who tested positive by PCR or rapid antigen test or participants with history of having signs and symptoms mild COVID-19 illness (e.g., fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell) but who did not have shortness of breath, dyspnea, or abnormal chest imaging are eligible for the study if they fully recovered a minimum of 6 months before enrollment.
• Female participant is eligible if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:
• is of childbearing potential and must have a negative pregnancy test prior to study vaccinations and agree to use an effective method of birth control as deemed appropriate by the investigator (e.g., hormonal contraceptive, barrier contraceptive with additional spermicide, or an intrauterine device) beginning \>30 days prior to the first study vaccine administration and continuing for a minimum of 30 days after the last dose of study vaccine.
• is not of childbearing potential, defined as postmenopausal (a minimum of 12 months with no menses without an alternative medical cause) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy).
• Male participant is eligible to participate if he agrees to the following requirements from the time of first study vaccination until at least 30 days after the last dose of study vaccine:
• Be abstinent from heterosexual intercourse with a female of childbearing potential OR
• Must agree to use a male condom. In addition to male condom use, an effective method of contraception may be considered in female partners of male participants AND
• Must refrain from sperm donation
• Have previously received 2 or more doses of a licensed COVID-19 vaccine(s) with the last dose administered a minimum of 6 months (24 weeks) prior to enrollment. Participants vaccinated with any of the vaccines approved by Health Canada for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) in individuals 18 years of age and older are eligible for the study. This includes the following COVID-19 vaccines: Moderna Spikevax®, Pfizer-BioNTech Comirnaty®, AstraZeneca Vaxzevria®, Janssen Jcovden® (Johnson \& Johnson), Novavax Nuvaxovid® and Medicago Covifenz®. Participants who received one or more doses of VBI-2902a, VBI-2905a or any other COVID-19 vaccines that are either investigational or not approved by Health Canada are not eligible for the study.

You may not qualify if:

• History of COVID-19 illness of moderate or greater severity, defined as one of the following:
• Moderate Illness: Individuals who show evidence of lower respiratory disease during clinical assessment or imaging and who have an oxygen saturation (SpO2) ≥94% on room air at sea level.
• Severe COVID-19 illness: Individuals who have SpO2 \<94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) \<300 mm Hg, a respiratory rate \>30 breaths/min, or lung infiltrates \>50%.
• Critical COVID-19 illness: Individuals who have respiratory failure, septic shock, and/or multiple organ dysfunction.
• Positive SARS-CoV-2 PCR or rapid antigen test at screening.
• History of SARS or MERS.
• Participant with a history of an underlying clinically significant acute or chronic medical condition or physical examination findings for which, in the opinion of the investigator, participation in the study would not be in the best interest of the participant (e.g., could compromise participant's wellbeing) or that could prevent, limit, or confound the protocol-specified assessments.
• Individuals with medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• History of cancer requiring chemotherapy or radiation within 5 years.
• Lack of participant's capacity (mental, social, behavioral), in the investigator's judgement, to provide informed consent for participation in the study.
• Known or suspected impairment of immunological function, including but not limited to:
• autoimmune diseases (e.g., multiple sclerosis, type 1 diabetes, myasthenia gravis, Crohn's disease and other inflammatory bowel diseases, celiac disease, systemic lupus erythematosus, scleroderma, including diffuse systemic form and CREST syndrome, systemic sclerosis, dermatomyositis polymyositis, rheumatoid arthritis, juvenile idiopathic arthritis, autoimmune thyroiditis - including Hashimoto thyroiditis, Grave's or Basedow's disease, immune thrombocytopenic purpura, autoimmune hemolytic anemia, autoimmune hepatitis, psoriasis, vitiligo, vasculitis, Guillain- Barré syndrome, transverse myelitis, Addison's disease, Bell's palsy and alopecia areata) or abnormal or positive test result for any of the following tests at the study screening visit:
• ANA (Antinuclear Antibody)
• RF (Rheumatoid Factor)
• tTG-IgA (Tissue Transglutaminase IgA Antibody)

Sponsors & Collaborators

• VBI Vaccines Inc.: lead

Study Sites (4)

Canadian Center for Vaccinology

Halifax, Nova Scotia, B3K 6R8, Canada

Location

Red Maple Trials

Ottawa, Ontario, K1H 1E4, Canada

Location

Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

CHU de Québec Université Laval

Québec, Quebec, G1E 7G9, Canada

Location

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Severe Acute Respiratory Syndrome

Condition Hierarchy (Ancestors)

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

Study Officials

• William Cameron, MD

  Ottawa Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2022
• First Posted: November 14, 2022
• Study Start: March 1, 2023
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: April 4, 2023

Record last verified: 2023-03

Locations

CA (4)