Official Title
A Phase I, Dose-escalation Study to Assess the Safety, Reactogenicity, and Immunogenicity of Two Doses of an Adjuvanted Novel Pancoronavirus Vaccine (Cov- RBD-scNP-001) in 18 Through 55-year-old Healthy Participants
Brief Summary

Coronaviruses (CoVs) have caused the severe acute respiratory syndrome (SARS) outbreak,the Middle East Respiratory Syndrome (MERS) outbreak, and now the severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Although there are severalapproved or authorized vaccines for SARS-CoV-2, there are currently no vaccines approvedto prevent diseases caused by multiple different coronaviruses. Two countermeasures withpromise for controlling coronavirus outbreaks are recombinant neutralizing antibodies andvaccines directed against the virus. Between these two countermeasures, the ultimatesolution to control the current COVID-19 pandemic and future CoV outbreaks is apancoronavirus vaccine. In particular, a vaccine that can induce broader protection andcan prevent severe disease caused by current SARS-CoV-2 variants of concern would helpmitigate significant morbidity and mortality following SARS-CoV-2 infection.Additionally, an optimal pancoronavirus vaccine would prevent severe disease from otherSARS-related viruses in the genus of coronaviruses-betacoronavirus-that are responsiblefor past outbreaks or could cause the next major outbreak in humans. Such a broadlyactive coronavirus vaccine would be an impactful first step towards preventing alllife-threatening coronavirus human disease.The proposed vaccine immunogen (Cov-RBD-scNP-001) is composed of an engineered receptorbinding domain (RBD) of SARS-CoV-2 WA-1 covalently linked in vitro to the surface of aHelicobacter pylori ferritin protein nanoparticle (RBD-scNP). The RBD has been engineeredat two sites to improve its expression. The protein nanoparticle is composed of 24individual ferritin subunits each of which can have a SARS-CoV-2 WA-1 RBD attached to itvia a nine amino acid linker. The protein nanoparticle will be delivered with 3M-052-AFadjuvant - a TLR 7/8 agonist.

Detailed Description

This is a single-site Phase I clinical trial in up to 51 males and non-pregnant,
non-lactating women, 18 to 55 years old, inclusive, who are in good health and meet all
eligibility criteria. The clinical trial is designed to assess the safety, reactogenicity
and immunogenicity of two doses, one each, administered on Days 1 and 29 of the
Cov-RBD-scNP-001 vaccine administered at three dosage levels - a 50 mcg (Low Dose Cohort)
followed by a 100 mcg (Medium Dose Cohort) and lastly a 150 mcg (High Dose Cohort).

Participants will be sequentially enrolled in the Low Dose, Medium Dose, and High Dose
Cohorts. Within each dose cohort will be sentinel and expanded subgroups. Four
participants will be enrolled into the sentinel subgroup and 13 will be enrolled in the
expanded subgroup. The estimated time to complete enrollment is 6 months. The total
duration of participant participation is up to 14 months.

Follow-up study visits will occur at 3 days and at 1, 2 and 4 weeks after each
vaccination, as well as 6 and 12 months after the last vaccination. Solicited adverse
events will be assessed for 7 days following each vaccination. Unsolicited events will be
assessed for 28 days following each vaccination. Blood and mucosal samples will be
obtained for safety and immunogenicity assays at select study visits. Adverse events of
special interest (AESIs), Serious adverse events (SAEs), Medically attended adverse
events (MAAEs), New onset chronic medical conditions (NOCMCs), and potential
immune-mediated medical conditions will be collected from the first vaccination through
12 months after the last vaccination. Clinical safety laboratory evaluations will be
performed prior to, and 7 days post each vaccination and 28 days following the second
vaccination.

Nasal swabs will be self-collected or collected by staff at unscheduled illness visits to
evaluate breakthrough SARS-CoV-2 infection (symptomatic infection or asymptomatic
infection with a positive SARS-CoV-2 test outside the study).

Not yet recruiting
COVID-19 Respiratory Infection
SARS CoV 2 Infection
COVID-19 Vaccine

Biological: CoV-RBD-scNP-001 and 3M-052-AF

All subjects will receive the investigational vaccine CoV-RBD-scNP-001 adjuvanted with
3M-052-AF.

Eligibility Criteria

Inclusion Criteria:

1. Provide written informed consent prior to the initiation of any trial procedures.

2. Able to understand and agrees to comply with all planned trial procedures and be
available for all study visits.

3. Male, or non-pregnant, non-breastfeeding female, age 18-55 years, inclusive, at time
first study vaccination.

4. Women of childbearing potential must agree to use or have practiced true abstinence
or use at least one acceptable primary form of contraception.

Note: These criteria are applicable to females in a relationship with a male, and
who are of child-bearing potential).

Not of childbearing potential - post-menopausal females (defined as having a history
of amenorrhea for at least one year) or a documented status as being surgically
sterile (hysterectomy, bilateral oophorectomy, or Essure® placement).

True abstinence is 100% of time no sexual intercourse (male's penis enters the
female's vagina). (Periodic abstinence [e.g., calendar, ovulation, symptothermal,
post-ovulation methods] and withdrawal are not acceptable methods of contraception).

Acceptable forms of primary contraception include monogamous relationship with a
vasectomized partner who has been vasectomized for 180 days or more prior to the
participant's first vaccination, tubal ligation, intrauterine devices, birth control
pills, and injectable/implantable/insertable/transdermal hormonal birth control
products.

Must have used at least one acceptable primary form of contraception for at least 30
days prior to the first vaccination and continue at least one acceptable primary
form of contraception through 60 days after the last vaccination.

5. Women of childbearing potential must have a negative serum pregnancy test at
screening and a negative urine pregnancy test within 24 hours prior to each study
vaccination.

6. Male participants are eligible to participate if they agree to refrain from donating
sperm and to be abstinent from heterosexual intercourse with a female of
childbearing potential as their preferred and usual lifestyle or must agree to use a
male condom when engaging in any activity that allows for passage of ejaculate to
another person during the intervention period and for at least 90 days after the
last dose of study product.

7. In good general health

As determined by medical history and physical examination, including vital signs, to
evaluate acute or ongoing chronic medical diagnoses/conditions that have been
present for at least 90 days, which would affect the assessment of safety of
participants. Chronic medical diagnoses/ conditions should be stable for the last 30
days (i.e., no hospitalizations, ER, or urgent care for condition). This includes no
change in chronic prescription medication, dose, or frequency as a result of
deterioration of the chronic medical diagnosis/condition in the 30 days before study
vaccination Any prescription change that is due to change of health care provider,
insurance company, etc., or done for financial reasons, and in the same class of
medication, will not be considered a deviation of this inclusion criterion.
Participants may be on chronic or as needed (prn) medications if, in the opinion of
the participating site PI or appropriate sub-investigator, they pose no additional
risk to participant safety or assessment of reactogenicity and immunogenicity.

8. Reported receipt of a complete primary COVID-19 vaccine series and at least one
booster with last vaccination at least 16 weeks prior to study vaccine dose 1

A complete primary COVID-19 vaccine series is defined as two Pfizer or Moderna
COVID-19 vaccines.

Booster may be either homologous or heterologous to the primary vaccine series and
must be an FDA authorized/approved vaccine though authorized/approved doses may have
been received as part of a clinical trial.

9. Clinical screening laboratory evaluations are within normal reference ranges or
grade 1 with no clinical significance (NCS) per investigator discretion.

Ferritin, Iron, and Total Iron Binding Capacity (TIBC)

(White Blood Cells [WBCs] with differential, hemoglobin [Hgb], platelets [PLTs],
Alanine Transaminase [ALT], Aspartate Transaminase [AST], Creatinine [Cr], Alkaline
Phosphatase [ALP], Total Bilirubin [T. Bili]). ALT, AST, ALP, and creatinine values
that are below the reference range will not be exclusionary as long as these values
below reference range are clinically insignificant.

10. Must agree to have samples stored for secondary research.

Exclusion Criteria:

1. Positive SARS-CoV-2 PCR at screening.

2. Abnormal vital signs (Grade 1 or higher) at screening.

Grade 1 or higher is equivalent to:

Systolic blood pressure (SBP) ≥ 141 mmHg or ≤ 89 mmHg

Diastolic blood pressure (DBP) ≥ 91 mmHg

Heart rate (HR) is ≥ 101 beats per minute or ≤ 50 beats per minute

Oral temperature ≥ 38.0°C (100.4°F)

3. Body mass index (BMI) of < 18 kilograms/square meter (kg/m^2) or > 35 kg/m^2
(inclusive) at screening

4. History of SARS-CoV-2 infection or receipt of any COVID-19 vaccine < 16 weeks prior
to study vaccination.

5. Woman who is pregnant or breastfeeding.

6. Blood or plasma donation within 4 weeks prior to study vaccination.

7. Receipt of antibody or blood-derived products (except Rho D immunoglobulin) within
90 days prior to study vaccination.

8. Any self-reported or medically documented significant medical or psychiatric disease
or condition(s) that, in the opinion of the site Principal Investigator (PI) or
appropriate sub-investigator, precludes study participation.

Significant medical or psychiatric conditions include but are not limited to
respiratory disease (e.g., chronic obstructive pulmonary disease [COPD]) requiring
daily medications currently, history of asthma in the past 5 years, or any treatment
of exacerbation of an underlying respiratory disease in the last 5 years.
Significant kidney disease, liver disease, or cardiovascular disease (e.g.,
congestive heart failure, cardiomyopathy, ischemic heart disease), including any
history of myocarditis or pericarditis, or uncontrolled cardiac arrhythmia.
Neurological or neurodevelopmental conditions (e.g., history of Bell's palsy,
history of four or more migraine headaches in the past 12 months that interfered
with normal daily activity or any migraine headache in the past 5 years that
required emergency or inpatient medical care, epilepsy, seizures in the last 5
years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome,
encephalomyelitis, transverse myelitis, stroke or transient ischemic attack,
multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis,
Creutzfeldt-Jakob disease, or Alzheimer's disease). Ongoing malignancy or recent
diagnosis of malignancy in the last five years excluding treated basal cell and
squamous cell carcinoma of the skin, which are allowed. Any autoimmune disease,
including hypothyroidism without a defined non-autoimmune cause.

9. Has an acute illness, as determined by the site PI or appropriate sub-investigator,
within 72 hours prior to study vaccination.

An acute illness that is nearly resolved with only minor residual symptoms remaining
is allowable if, in the opinion of the site PI or appropriate subinvestigator, the
residual symptoms will not interfere with the ability to assess safety parameters as
required by the protocol.

10. Has known human immunodeficiency virus, hepatitis B or hepatitis C infection at
screening.

11. Has a positive test result for hepatitis B surface antigen, hepatitis C virus
antibody, or human immunodeficiency virus antigen or antibody at screening.

12. Has an ongoing symptomatic condition for which there are ongoing medical
investigations, but no diagnosis or treatment plan.

13. Has any confirmed or suspected immunosuppressive or immunodeficient state such as
asplenia, recurrent severe infections and chronic immunosuppressant medication
within the past 6 months

Chronic meaning more than 14 continuous days

14. Has taken oral or parenteral (including intra-articular) corticosteroids of any dose
within 30 days prior to the first study vaccination. Intranasal, ophthalmic, or
topical (skin or eyes) corticosteroids are permitted.

15. Has any significant disorder of coagulation requiring ongoing or intermittent
treatment.

16. Has participated in another investigational study involving any IP within 60 days,
or 5 half-lives, whichever is longer, before the first vaccine administration.

17. Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis,
generalized urticaria, angioedema, other significant reaction) to any previous
licensed or unlicensed vaccine or to the candidate vaccine components.

18. Receipt of inactivated/subunit vaccine within 14 days prior to vaccine
administration or live vaccine within 28 days prior to vaccine administration.

19. Plan to receive a COVID-19 booster vaccine within the 209 days following the first
study vaccination.

20. Planned international travel in the period between vaccination through Study Day 57
visit.

21. Has a history of alcohol or drug abuse within 3 years prior to study vaccination.

22. Has any diagnosis, current or past, of schizophrenia, bipolar disease or other
psychiatric diagnosis that may interfere with participant compliance or safety
evaluations.

23. Has been hospitalized for psychiatric illness, history of suicide attempt, or
confinement for danger to self or others within 5 years prior to study vaccination.

24. Has a history of receipt of an investigational ferritin-based vaccine.

25. Has any abnormality or permanent body art (e.g., tattoo) that, in the opinion of the
investigator, would obstruct the ability to observe local reactions at the injection
site

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: 55 Years
Locations

Not Provided

Contacts

Emmanuel Walter, MD
919-620-5346
kristen.gunnell@duke.edu

Kristen Gunnell, MS
919-684-8891
kristen.gunnell@duke.edu

Not Provided

National Institute of Allergy and Infectious Diseases (NIAID)
NCT Number
MeSH Terms
Infections
Communicable Diseases
COVID-19
Respiratory Tract Infections
MEDI9197