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Evaluating the Safety, Tolerability and Immunogenicity of bacTRL-Spike Vaccine for Prevention of COVID-19

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ClinicalTrials.gov Identifier: NCT04334980
Recruitment Status : Not yet recruiting
First Posted : April 6, 2020
Last Update Posted : April 22, 2020
Sponsor:
Information provided by (Responsible Party):
Symvivo Corporation

Brief Summary:
Protocol bacTRL-Spike-1 will be the first-in-human study of bacTRL-Spike, and the first-in-human use of orally delivered bacTRL. Each oral dose of bacTRL-Spike contains bacterial medium with either 1 billion (Group 1A), 3 billion (Group 2A) or 10 billion (Group 3A) colony-forming-units of live Bifidobacterium longum, which has been engineered to deliver plasmids containing synthetic DNA encoding spike protein from SARS-CoV-2. Placebo will consist of bacterial medium without bacteria.

Condition or disease Intervention/treatment Phase
COVID-19 Biological: bacTRL-Spike Other: Placebo Phase 1

Detailed Description:

Protocol bacTRL-Spike-1 will be the first-in-human study of bacTRL-Spike, and the first-in-human use of orally delivered bacTRL. The trial is designed to evaluate the safety and tolerability of orally delivered bacTRL-Spike vaccine in healthy adults.

Total anticipated enrollment is n=84, including 63 receiving active vaccine in bacterial medium and 21 receiving placebo (bacterial medium only). The distribution of the sample size will be as follows:

  • Group 1A (n=21): Single dose of bacTRL-Spike, equivalent to 1 billion colony forming units (cfu) of Bifidiobacterium longum;
  • Group 1B (n=7): Single dose of placebo;
  • Group 2A (n=21): Single dose of bacTRL-Spike, equivalent to 3 billion cfu of B. longum;
  • Group 2B (n=7): Single dose of placebo;
  • Group 3A (n=21): Single dose of bacTRL-Spike, equivalent to 10 billion cfu of B. longum;
  • Group 3B (n=7): Single dose of placebo. The planned trial duration is 18 months.

Each participant will remain in the trial for 12-13 months, including a screening phase of up to 14 days, intervention phase of 1 day and follow-up phase of 12 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: This is an observer-blinded study. Both participants and the study center staff performing outcome measurement are blinded; oral vaccines will be prepared by qualified unblinded study personnel who have no other role in the study. Testing laboratory personnel will also be blinded.
Primary Purpose: Prevention
Official Title: A Phase 1, Randomized, Observer-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability and Immunogenicity of the bacTRL-Spike Oral Candidate Vaccine for the Prevention of COVID-19 in Healthy Adults
Estimated Study Start Date : April 30, 2020
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : December 31, 2021

Arm Intervention/treatment
Experimental: bacTRL-Spike Group 1A
• Group 1A (n=21): Single dose of bacTRL-Spike, equivalent to 1 billion colony forming units (cfu) of Bifidiobacterium longum;
Biological: bacTRL-Spike
Each oral dose of bacTRL-Spike contains bacterial medium with either 1 billion (Group 1A), 3 billion (Group 2A) or 10 billion (Group 3A) colony-forming-units of live Bifidobacterium longum, which has been engineered to deliver plasmids containing synthetic DNA encoding spike protein from SARS-CoV-2.

Experimental: bacTRL-Spike Group 2A
• Group 2A (n=21): Single dose of bacTRL-Spike, equivalent to 3 billion colony forming units (cfu) of Bifidobacterium longum;
Biological: bacTRL-Spike
Each oral dose of bacTRL-Spike contains bacterial medium with either 1 billion (Group 1A), 3 billion (Group 2A) or 10 billion (Group 3A) colony-forming-units of live Bifidobacterium longum, which has been engineered to deliver plasmids containing synthetic DNA encoding spike protein from SARS-CoV-2.

Experimental: bacTRL-Spike Group 3A
• Group 3A (n=21): Single dose of bacTRL-Spike, equivalent to 10 billion colony forming units (cfu) of Bifidobacterium longum;
Biological: bacTRL-Spike
Each oral dose of bacTRL-Spike contains bacterial medium with either 1 billion (Group 1A), 3 billion (Group 2A) or 10 billion (Group 3A) colony-forming-units of live Bifidobacterium longum, which has been engineered to deliver plasmids containing synthetic DNA encoding spike protein from SARS-CoV-2.

Placebo Comparator: Placebo Group 1B
• Group 1B (n=7): Single dose of placebo;
Other: Placebo
Placebo consists of bacterial medium without bacteria.

Placebo Comparator: Placebo Group 2B
• Group 2B (n=7): Single dose of placebo;
Other: Placebo
Placebo consists of bacterial medium without bacteria.

Placebo Comparator: Placebo Group 3B
• Group 3B (n=7): Single dose of placebo.
Other: Placebo
Placebo consists of bacterial medium without bacteria.




Primary Outcome Measures :
  1. Frequency of Adverse Events [ Time Frame: Up to12 months post-vaccination ]
    Adverse events (specifically including incidence of gastrointestinal-associated events) following administration of oral bacTRL-Spike


Secondary Outcome Measures :
  1. SARS-CoV-2 antibodies [ Time Frame: Baseline (pre-vaccination), and 1, 3 and 12 months post-vaccination ]
    Antibody against SARS-CoV-2 Spike protein

  2. Incidence of COVID-19 infection [ Time Frame: Up to 12 months post-vaccination ]
    Incidence and clinical phenotype of confirmed and probable COVID-19 infection among vaccinated participants, based on current public health definitions

  3. bacTRL-Spike in stool post-vaccination [ Time Frame: Days 7, 14, 21, and 1 and 3 months post-vaccination ]
    Isolation of viable bacTRL-Spike from stool post-vaccination

  4. Seroconversion of circulating anti-Spike IgG antibodies & stability of serum IgG titers [ Time Frame: Up to 12 months post-vaccination ]
    Collection of biological samples for future studies to understand immunity against SARS-CoV-2.

  5. Effectiveness of intestinal colonization of the probiotic-based bacTRL-Spike oral vaccine [ Time Frame: Up to 12 months post-vaccination ]
    Collection of biological samples for future studies to understand immunity against SARS-CoV-2.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   19 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age 19-45 years inclusive at time of enrolment;
  2. Capable to and does provide written informed consent;
  3. Able to understand and agrees to comply with planned study procedures and be available for all study visits;
  4. Body Mass Index 18-35 kg/square meter, inclusive, at screening;
  5. Male or non-pregnant, non-breastfeeding females who agree to comply with applicable contraceptive requirements of the protocol (see Table 1 Acceptable Contraceptive Methods.) Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to initiation of vaccination;
  6. Pulse no greater than 100 beats per minute;
  7. Systolic blood pressure (BP) is 85 to 150 mmHg, inclusive;
  8. Clinical screening laboratory evaluations [white blood cell (WBC), hemoglobin (Hgb), platelets (PLTs), alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cr), alkaline phosphatase (ALP), total bilirubin (T. Bili), Lipase, prothrombin time (PT), partial thromboplastin time (PTT), and C-reactive protein (CRP) reveal no clinically significant abnormalities;
  9. Agree to have samples stored for secondary research related to coronaviruses.

Exclusion Criteria:

  1. Positive pregnancy test either at screening or just prior to vaccine administration.
  2. Female participant who is breastfeeding or plans to breastfeed from the time of the study vaccination through 3 months after the study vaccination.
  3. Has acute or chronic inflammatory condition of the gastrointestinal tract including, but not limited to, Crohn's disease, ulcerative colitis, gastritis, proctitis, or any other inflammatory bowel disorder.
  4. Has any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, precludes study participation (including but not limited to acute, subacute, intermittent or chronic medical disease or condition that would place the participant at an unacceptable risk of injury, render the participant unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the participant's successful completion of this trial.)
  5. Presence of self-reported or medically documented significant medical or psychiatric condition(s).

    Significant medical or psychiatric conditions include but are not limited to:

    • Respiratory disease (e.g., chronic obstructive pulmonary disease, asthma) requiring daily medications currently or any treatment of respiratory disease exacerbations (e.g., asthma exacerbation) in the last 5 years. Asthma medications: inhaled, oral, or intravenous (IV) corticosteroids, leukotriene modifiers, long and short acting beta agonists, theophylline, ipratropium, biologics.
    • Significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease) or history of myocarditis or pericarditis as an adult.
    • Neurological or neurodevelopmental conditions (e.g., migraines, epilepsy, stroke, seizures in the last 3 years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, encephalomyelitis or transverse myelitis).
    • Ongoing malignancy or recent diagnosis of malignancy in the last five years excluding basal cell and squamous cell carcinoma of the skin, which are allowed.
    • An autoimmune disease, including hypothyroidism without a defined non-autoimmune cause, localized or history of psoriasis.
    • An immunodeficiency of any cause.
    • Presence of an indwelling prosthetic device or other foreign material.
  6. Has an acute illness, as determined by the site PI or appropriate sub-investigator, with or without fever (oral temperature >38.0 degrees Celsius) within 72 hours prior to the vaccination. (An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.)
  7. Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or HIV types 1 or 2 antibodies at screening.
  8. Has participated in another investigational study involving any investigational product (study drug, biologic or device) within 60 days, or 5 half-lives, whichever is longer, before the study vaccine administration.
  9. Currently enrolled in or plans to participate in another clinical trial with an investigational agent (including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication) that will be received during the trial period.
  10. Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to any previous licensed or unlicensed vaccines.
  11. Chronic use (more than 14 continuous days) of any medications that may be associated with impaired immune responsiveness. Including, but not limited to: systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or other similar or toxic drugs during the preceding 6-month period prior to vaccine administration (Day 1). The use of low dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted.
  12. Received immunoglobulins and/or any blood or blood products within the 4 months before the study vaccine administration or at any time during the study.
  13. Has any blood dyscrasias or significant disorder of coagulation.
  14. Has any chronic liver disease, including fatty liver.
  15. Has a history of alcohol abuse or other recreational drug (excluding cannabis) use within 6 months before the study vaccine administration.
  16. Received or plans to receive a licensed, live vaccine within 4 weeks before or after each vaccination.
  17. Received or plans to receive a licensed, inactivated vaccine within 2 weeks before or after each vaccination.
  18. Receipt of any other SARS-CoV-2/COVID-19, or other experimental coronavirus vaccine at any time prior to or during the study.
  19. Known current or previous laboratory-confirmed SARS CoV-1 OR SARS-CoV-2/COVID-19 infection as documented by a positive PCR test from a nasal swab OR positive serology.
  20. Known close contact of anyone with laboratory-confirmed SARS-CoV-2/COVID-19 infection within 2 weeks prior to vaccine administration.
  21. Has traveled outside Canada for any duration within 30 days before the study vaccination.
  22. Household contact including neonates up to the age of 28 days with any medical condition or taking medications that may result in immunosuppression.
  23. Current use of any antibiotics or probiotic supplements within 7 days prior to vaccination and any anticipated use for 7 days post vaccination.
  24. The participant must agree to refrain from donating blood or plasma during the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04334980


Contacts
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Contact: Alexander Graves, PhD, MBA (604) 428-7474 bd@symvivo.com
Contact: Michelle Jones, RN, M.Sc., MBA 604-428-7474 bd@symvivo.com

Locations
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Canada, British Columbia
Vaccine Evaluation Center, BC Children's Hospital Research Institute, University of British Columbia.
Vancouver, British Columbia, Canada, V5Z 4H4
Contact: Mistin Wilkinson       mistin.wilkinson@bcchr.ubc.ca   
Principal Investigator: Manish Sadarangani, BM BCh DPhil         
Sub-Investigator: Soren Gantt, MD PhD         
Sub-Investigator: Mel Krajden, MD PhD         
Sub-Investigator: Muhammad Morshed, PhD         
Canada, Nova Scotia
Canadian Center for Vaccinology Dalhousie University, IWK Health Centre
Halifax, Nova Scotia, Canada, B3K 6R8
Contact: Jill Mutch       jill.mutch@iwk.nshealth.ca   
Sub-Investigator: Scott Halperin, MD         
Principal Investigator: Joanne Langley, MD, MSc, FRCPC         
Sub-Investigator: Shelly McNeil, MD, FRCPC         
Sponsors and Collaborators
Symvivo Corporation
Investigators
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Study Director: Eric L Sievers, MD Chief Medical Officer
Study Chair: Manish Sadarangani, MRCPCH, DPHIL Principal Investigator
Principal Investigator: Joanne Langley, MD, FRCPSC Principal Investigator
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Responsible Party: Symvivo Corporation
ClinicalTrials.gov Identifier: NCT04334980    
Other Study ID Numbers: bacTRL-Spike-1
First Posted: April 6, 2020    Key Record Dates
Last Update Posted: April 22, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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