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.
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=24. The distribution of the sample size will be as follows:
- Group 1 (n=3; Sentinel +2): Single dose of bacTRL-Spike, equivalent to 1 billion colony
forming units (cfu) of Bifidobacterium longum (B. longum);
- Group 2 (n=3; Sentinel +2): Single dose of bacTRL-Spike, equivalent to 3 billion cfu of
B. longum;
- Group 3 (n=3; Sentinel +2): Single dose of bacTRL-Spike, equivalent to 10 billion cfu of
B. longum;
- Group 4 (n=3): Single Data and Safety Monitoring Board (DSMB)-defined dose of
bacTRL-Spike among subjects 56 years of age and older.
- Group 5 (n=12): DSMB-defined prime and boost doses of bacTRL-Spike delivered with a
28-day intervening interval.
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 28 days, intervention phase of 1 day and follow-up phase of 12 months.
Biological: bacTRL-Spike
Each oral dose of bacTRL-Spike contains bacterial medium with either 1 billion (Group 1), 3 billion (Group 2) or 10 billion (Group 3) colony-forming-units of live Bifidobacterium longum, which has been engineered to deliver plasmids containing synthetic DNA encoding spike protein from SARS-CoV-2.
INCLUSION CRITERIA
1. Age 18 years inclusive at time of enrollment and older;
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 18-32 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:
- Absolute neutrophil count (ANC) ≥1500 cells/mm3
- Hemoglobin ≥12.0 g/dL for men and ≥11.0 g/dL for women
- Platelet count ≥120,000/mm3
- Creatinine clearance (CrCl) >80 mL/min ); Refer to the calculator located on the
Frontier Science and Technology Research Foundation (FSTRF) website (at
https://www.frontierscience.org/): Calculated Creatinine Clearance -
Cockcroft-Gault Equation (Adult).
- Aspartate aminotransferase (AST) <1.25 x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) <1.25 x ULN
- Alkaline phosphatase <2.0 x ULN
- Total bilirubin <1.1 x ULN
- Lipase <1.1 x ULN
- Prothrombin time (PT) <1.1 x ULN
- Partial thromboplastin time (PTT) <1.1 x ULN
- CRP < 2.0 x ULN
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, history, or behavior that may predispose to more severe
COVID-19 infection, including hypertension, diabetes, current vaping and/or smoking,
history of chronic smoking within the prior year (average of at least one cigarette
per day or more), or body mass index of greater than 32; stable hypertension
controlled with a stable dose of medication is permitted.
5. 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.)
6. 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.
- Excluded 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 or are immune-suppressed.
7. Has an acute illness, as determined by the site PI or appropriate sub-investigator,
with or without fever (oral temperature >38.0 degrees Celsius [100.4 degrees
Fahrenheit]) within 72 hours prior to study vaccination administration.
8. Has a positive test result for hepatitis B surface antigen, hepatitis C virus
antibody, or human immunodeficiency virus (HIV) types 1 or 2 antibodies at screening.
9. 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 study vaccine administration.
10. 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.
11. 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.
12. Chronic use (more than 14 continuous days) or anticipated use within the next 6 months
of any medications that may be associated with impaired immune responsiveness.
Including, but not limited to the following excluded drugs: 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.
13. Received immunoglobulins and/or any blood or blood products within the 4 months before
study vaccine administration or at any time during the study.
14. Has any blood dyscrasias or significant disorder of coagulation.
15. Has any chronic liver disease, including fatty liver.
16. Has a history of alcohol or drug abuse or tests positive for drugs of abuse at
screening.
17. Received or plans to receive a licensed, live vaccine within 4 weeks before or after
each vaccination.
18. Received or plans to receive a licensed, inactivated vaccine within 2 weeks before or
after each vaccination.
19. Receipt of any other SARS-CoV-2/COVID-19, or other experimental coronavirus vaccine at
any time prior to or during the study.
20. 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.
21. Known close contact of anyone with laboratory-confirmed SARS-CoV-2/COVID-19 infection
within 2 weeks prior to vaccine administration.
22. Has traveled outside Australia for any duration within 30 days before study
vaccination.
23. Currently working in occupation with high risk of exposure to SARS-CoV-2 (e.g., health
care worker, emergency response personnel).
24. Allergy to BOTH amoxicillin (or any penicillin derivative) AND erythromycin
25. Household contact, including neonates up to the age of 28 days, with any medical
condition or taking medications that may result in immunosuppression.
26. The participant must agree to refrain from donating blood or plasma during the study.
27. Excluded medications (summarized): Excluded asthma medications: inhaled, oral, or
intravenous (IV) corticosteroids, leukotriene modifiers, long and short acting beta
agonists, theophylline, ipratropium, biologics; Excluded immunosuppressive drugs:
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); Excluded other medications - current use of any antibiotics,
probiotic supplements, H2 blockers or proton pump inhibitors within 7 days prior to
vaccination and any anticipated use for 7 days post vaccination.
Nucleus Network Pty Ltd Brisbane (QPharm)
Brisbane, Queensland, Australia