Safety, Tolerability, and Immunogenicity of the COVID-19 Vaccine Candidates VBI-2902a and VBI-2905a

• ClinicalTrials.gov Identifier: NCT04773665
• Recruitment Status: Recruiting
• First Posted: February 26, 2021
• Last Update Posted: October 8, 2021
• Sponsor: VBI Vaccines Inc.
• Information provided by (Responsible Party): VBI Vaccines Inc.

Tracking Information

• First Submitted Date: February 24, 2021
• First Posted Date: February 26, 2021
• Last Update Posted Date: October 8, 2021
• Actual Study Start Date: March 15, 2021
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 1, 2021)

• Rate and severity of local and systemic solicited adverse events after each study vaccination [ Time Frame: Through 7 days after each study vaccination ]
• Rate and severity of unsolicited adverse events after each study vaccination [ Time Frame: Through 28 days after each study vaccination ]
• Rate and severity of medically attended adverse events after each study vaccination [ Time Frame: Through 28 days after each study vaccination ]
• Rate of serious adverse events after each study vaccination [ Time Frame: Through 28 days after each study vaccination ]
• Adverse events leading to discontinuation of study vaccination [ Time Frame: Through study completion, approximately 1 year ]
• Adverse events leading to study discontinuation [ Time Frame: Through study completion, an approximately 1 year ]
• Rate and severity of laboratory abnormalities (hematology, biochemistry, urinalysis) [ Time Frame: Through 28 days after each study vaccination ]

Original Primary Outcome Measures (submitted: February 25, 2021)

• Rate and severity of local and systemic solicited adverse events [ Time Frame: Through study completion, an average of 1 year ]
• Rate and severity of unsolicited adverse events [ Time Frame: During 28 days after each study vaccination ]
• Rate and severity of medically attended adverse events [ Time Frame: Through study completion, an average of 1 year ]
• Rate of serious adverse events [ Time Frame: Through study completion, an average of 1 year ]
• Adverse events leading to discontinuation of study vaccination [ Time Frame: Through study completion, an average of 1 year ]
• Adverse events leading to study discontinuation [ Time Frame: Through study completion, an average of 1 year ]
• Rate and severity of laboratory abnormalities (hematology, biochemistry, urinalysis) [ Time Frame: Through study completion, an average of 1 year ]

Current Secondary Outcome Measures (submitted: October 1, 2021)

• Rate and severity of unsolicited adverse events [ Time Frame: Through study completion, approximately 1 year ]
• Rate and severity of medically-attended adverse events [ Time Frame: Through study completion, approximately 1 year ]
• Rate and severity of serious adverse events [ Time Frame: Through study completion, approximately 1 year ]
• Rate and severity of laboratory abnormalities (hematology, biochemistry, urinalysis) [ Time Frame: Through study completion, approximately 1 year ]
• Geometric Mean Titer (GMT) and the geometric mean fold increase in serum antibody titer post-vaccination over baseline [ Time Frame: Study Days 56 and 224 (Phase 1a) and 56 and 168 (Phase 1b) ]
• GMT and the geometric mean fold increase in serum antibody titer post-vaccination over baseline [ Time Frame: Study Days 7, 28, 35, 56, 112, 224 and 336 (Phase 1a); Days 7, 14, 28, 56, 84, 168 and 336 (Phase 1b, groups G4 and G5); Days 7, 14, 28, 35, 42, 56, 84, 168 and 336 (Phase 1b, group G6) ]

Original Secondary Outcome Measures (submitted: February 25, 2021)

• Geometric Mean Titer (GMT) and the geometric mean fold increase in serum virus-neutralizing activity in a subset of participants post-vaccination over baseline [ Time Frame: Study Day 56 ]
• GMT and the geometric mean fold increase in serum receptor binding domain (RBD) antibody titers measured by ELISA post-vaccination over baseline [ Time Frame: Study Day 56 ]
• GMT and the geometric mean fold increase in serum virus-neutralizing activity in a subset of participants post-vaccination over baseline [ Time Frame: Days 7, 28, 35, 56 ]
• GMT and the geometric mean fold increase in serum RBD antibody titers measured by ELISA post-vaccination over baseline [ Time Frame: Days 7, 28, 35, 56 ]
• GMT and the geometric mean fold increase in serum spike protein antibody binding titers measured by ELISA post-vaccination over baseline [ Time Frame: Days 7, 28, 35, 56 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, and Immunogenicity of the COVID-19 Vaccine Candidates VBI-2902a and VBI-2905a
• Official Title: A Phase 1a/1b, Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of the COVID-19 (SARS-CoV-2) Vaccine Candidates VBI-2902a and VBI-2905a in Healthy Adults

Brief Summary

VBI-2902a and VBI-2905a are investigational vaccine candidates that use enveloped virus-like particle (eVLP) expression of a modified version of the SARS-CoV-2 spike (S) glycoprotein and are designed to induce neutralizing antibody and cell-mediated immune responses against the SARS-CoV-2 spike protein. VBI-2902a expresses the spike protein of SARS-CoV-2 Wuhan isolate (the first virus variant isolated in 2019 in Wuhan, China), while VBI-2905a expresses the spike protein of SARS-CoV-2 variant Beta (B.1.351 variant, first isolated in 2020 in South Africa).

The Phase 1a portion of this study tests one- and two-dose regimens of VBI- 2902a with 5 μg S protein content and aluminum phosphate (alum) adjuvant or placebo delivered by intramuscular (IM) injection. The Phase 1b portion of the study tests a one-dose regimen of VBI-2905a with 5 μg S protein content and alum adjuvant or placebo delivered by IM injection in participants previously vaccinated with an authorized mRNA COVID-19 vaccine, and a two-dose open-label regimen of VBI-2905a with 5 μg S protein content and alum adjuvant delivered by IM injection in participants not previously vaccinated with COVID-19 vaccines.

Detailed Description

Phase 1a:

The primary objective is to evaluate the safety and tolerability of VBI-2902a containing 5 μg of S protein in one- or two-dose regimens in healthy adults of 18-54 years of age.

The secondary objective is to evaluate the immunogenicity of VBI-2902a containing 5 μg of S protein in one- or two-dose regimens in healthy adults 18-54 years of age.

• Group G1 - 20 participants will receive VBI-2902a at a dose of 5 μg of S protein at Day 1 and placebo at Day 28.
• Group G2 - 20 participants will receive VBI-2902a at a dose of 5 μg of S protein at Days 1 and 28.
• Group G3 - 20 participants will receive placebo at Days 1 and 28.

An Independent Data Safety Monitoring Board (DSMB) will review blinded safety data (reactogenicity, adverse events (AEs) and safety laboratory assessments) at Day 7 after the first vaccination. The second vaccination will only be given if the DSMB confirms that Day 7 safety is acceptable and that stopping rules were not met. The DSMB will further review blinded post-vaccination safety through Day 35, 7 days after the second vaccination and through Day 56, 28 days after the second vaccination. The study will be unblinded following DSMB review of safety data collected through Day 56. Study participants will continue with study visits as planned up to 12 months of follow up after the first dose of study vaccine.

Phase 1b:

The primary objective is to evaluate the safety and tolerability of a one-dose regimen of VBI-2905a at a 5 μg dose level of S protein in healthy adults (age 18-54 years) who had been previously vaccinated with mRNA vaccines or a two-dose regimen of VBI-2905a at a 5 μg dose level of S protein in previously unvaccinated healthy adults (age 18-54 years).

The secondary objective is to evaluate the immunogenicity of a one-dose regimen of VBI-2905a at a 5 μg dose level of S protein in healthy adults (age 18-54 years) who had been previously vaccinated with mRNA vaccines or a two-dose regimen of VBI-2905a at a 5 μg dose level of S protein in previously unvaccinated healthy adults (age 18-54 years).

A total of 81 healthy adults, age 18-54 years, with no history of clinical or laboratory diagnosis of SARS-CoV- 2 infection or COVID-19 illness, will be enrolled in the Phase 1b part of the study. Of these, 54 participants who had been previously vaccinated with an authorized mRNA COVID-19 vaccine, including the second dose administered at least 4 months prior to enrollment, will be enrolled at the clinical sites in Canada and randomized at a 1:1 ratio to receive, in a blinded fashion, one dose of VBI-2905a or placebo:

• Group G4 - 27 participants will receive VBI-2905a at a dose of 5 μg of S protein at Day 1
• Group G5 - 27 participants will receive placebo at Day 1

Additionally, 27 participants who have not been previously vaccinated with any authorized or experimental COVID-19 vaccine will be enrolled into an open-label arm at the clinical site in Mexico City to receive two doses of VBI-2905a:

• Group G6 - 27 previously unvaccinated participants will receive VBI-2905a at a dose of 5 μg of S protein at Day 1 and Day 28

The DSMB will review blinded post-vaccination safety data 7 days after each vaccination (reactogenicity, AEs and safety laboratory assessments). In Phase 1b, the DSMB will review blinded Day 7 safety data after the first 10 participants in groups G4 and G5 (previously vaccinated) and 10 participants in group 6 (not previously vaccinated) have received the first dose. Only after the DSMB confirms that safety is acceptable and that stopping rules were not met will the enrollment in the respective study groups continue to its completion. The second vaccination in group G6 will proceed only after the DSMB has confirmed that the vaccine safety and tolerability is acceptable and that stopping rules were not met through 7 days after the first 10 participants have received the first dose of VBI-2905a.

• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

This is an observer-blinded study. Both participants and the study center staff performing outcome measurement are blinded; vaccines will be administered by qualified unblinded study personnel who have no other role in the study.

In an additional unblinded arm (Group G6), participants who have not been previously vaccinated with any authorized or experimental COVID-19 vaccine will be enrolled into an open-label arm to receive two doses of VBI-2905a.

Primary Purpose: Prevention

• Condition: Covid19

Intervention

• Biological: VBI-2902a
  VBI-2902a is an intramuscular injection of VBI-2902a investigational enveloped virus-like particle COVID-19 vaccine with aluminum phosphate adjuvant.
• Biological: Placebo
  0.9% sodium chloride
• Biological: VBI-2905a
  VBI-2905a is an intramuscular injection of VBI-2905a investigational enveloped virus-like particle COVID-19 vaccine with aluminum phosphate adjuvant.

Study Arms

• Experimental: Phase 1a, Group G1
  20 participants age 18-54 will receive VBI-2902a at a dose of 5 μg of S protein at Day 1 and placebo at Day 28
  Interventions:

  • Biological: VBI-2902a
  • Biological: Placebo
• Experimental: Phase 1a, Group G2
  20 participants age 18-54 will receive VBI-2902a at a dose of 5 μg of S protein at Days 1 and 28
  Intervention: Biological: VBI-2902a
• Placebo Comparator: Phase 1a, Group G3
  20 participants age 18-54 will receive placebo at Days 1 and 28
  Intervention: Biological: Placebo
• Experimental: Phase 1b, Group G4
  27 participants age 18-54 will receive VBI-2905a at a dose of 5 μg of S protein at Day 1
  Intervention: Biological: VBI-2905a
• Placebo Comparator: Phase 1b, Group G5
  27 participants age 18-54 will receive placebo at Day 1
  Intervention: Biological: Placebo
• Experimental: Phase 1b, Group G6
  27 previously unvaccinated participants age 18-54 will receive VBI-2905a at a dose of 5 µg of S protein at Day 1 and Day 28
  Intervention: Biological: VBI-2905a

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 1, 2021): 141
• Original Estimated Enrollment (submitted: February 25, 2021): 780
• Estimated Study Completion Date: November 2022
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

To be eligible for the study, each participant must satisfy all of the following criteria:

1. Healthy female and male participants 18 -54 years of age.

2. If female:

   1. 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 until the end of the study.

      OR

   2. is not of childbearing potential, defined as postmenopausal (12 months with no menses without an alternative medical cause) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy orhysterectomy).
3. Phase 1b, groups G4 and 5 only: previously received a full course (2 doses) of an authorized S protein mRNA COVID-19 vaccine (e.g. COVID-19 vaccines produced by Pfizer/BioNTech or Moderna) at least 4 months prior to enrollment.
4. Sign an informed consent document indicating understanding of the purpose of and procedures required for the study and willingness to participate in the study.

Exclusion Criteria

Participants with any of the following criteria will be excluded:

1. History of clinical or laboratory diagnosis of COVID-19 or SARS-CoV-2 infection.
2. Phase 1b, groups G4 and G5 only: Previous receipt of an experimental or authorized SARS-CoV-2 (COVID-19) vaccines other than an S-protein mRNA vaccine.
3. Phase 1a and Phase 1b, group G6 only: Previous receipt of an experimental or authorized SARS-CoV-2 (COVID-19) vaccine.
4. Positive PCR or rapid antigen test for SARS-CoV-2 at screening.

5. Individuals with chronic medical conditions, including any of the following:

   1. Diabetes mellitus Type 1 or Type 2
   2. Chronic pulmonary disease (e.g., COPD or Asthma)
   3. Hypertension (e.g., SBP >140 mmHg or DBP >90 mmHg)
   4. Chronic kidney disease (e.g., GFR <60 mL/min/1.73 m2)
   5. Chronic liver disease
   6. Obesity (e.g., BMI >30 kg/m2)
6. Any history of cancer requiring chemotherapy or radiation within 5years.
7. Other 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.
8. Lack of participant's capacity (mental, social, behavioral), in the investigator's judgement, to provide informed consent for participation in the study.

9. Known or suspected impairment of immunological function, including but not limited to autoimmune diseases:

   1. autoimmune diseases (e.g. multiple sclerosis, type 1 diabetes, myasthenia gravis, Crohn 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);
   2. secondary immunodeficiency disorders (e.g., Acquired Immunodeficiency Syndrome caused by Human Immunodeficiency Virus infection (HIV/AIDS), solid organ transplant,splenectomy);
   3. primary immunodeficiency disorders (e.g., common variable immune deficiency (CVID), Defective phagocytic cell function and neutropenia syndromes, complement deficiency).
10. History of allergic reactions or anaphylactic reaction to any vaccine component.
11. Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
12. Pregnant or breastfeeding or plans to conceive from 2 weeks before the study until the end of study.
13. Clinically significant abnormal physical examination, vital signs, or clinically significant abnormal values for hematology, serum chemistry or urinalysis at screening as determined by the investigator.
14. Any laboratory test abnormality that would be considered of Grade 1 severity or above (as per FDA grading guidelines) and is considered as clinically significant by the investigator. Grade 2 severity or above is exclusionary, regardless of clinical assessment.
15. Has received blood products or immunoglobulin within 90 days of enrollment or is likely to require blood products during the study period.
16. Chronic administration (defined as more than 14 days in total) of immune-suppressive or other immune-modifying drug within six months prior to the product dose (for corticosteroids, this is defined as prednisone ≥20 mg/day or equivalent). Inhaled and topical steroids are allowed.
17. Immunization with attenuated vaccines (e.g., measles, mumps, and rubella vaccine) within 4 weeks prior to enrollment.
18. Immunization with inactivated vaccines (e.g., influenza) within 2 weeks prior to enrolment.
19. Participation in another clinical study within 30 days.
20. Any skin abnormality or tattoo that would limit post-vaccination injection site assessment.
21. Family members of study site personnel.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 54 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Francisco Diaz-Mitoma, MD, PhD; 613-729-4200; fdiazmitoma@vbivaccines.com

Contact: Bebi Yassin-Rajkumar, MSc; 613-729-4200 Ext. 151; byassin-rajkumar@vbivaccines.com

• Listed Location Countries: Canada, Mexico

Administrative Information

• NCT Number: NCT04773665
• Other Study ID Numbers: VBI-2902a-CT01
• 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: Not Provided
• Responsible Party: VBI Vaccines Inc.
• Study Sponsor: VBI Vaccines Inc.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Joanne M Langley, MD; Canadian Center for Vaccinology
• Principal Investigator: William Cameron, MD; Ottawa Hospital

• PRS Account: VBI Vaccines Inc.
• Verification Date: October 2021