This study will be a phase-1, open-label, placebo-controlled, evaluation of two-dosagesof a live, recombinant Newcastle disease virus expressing the spike protein of SARS-CoV-2(NDV-HXP-S), an investigational product for IN, IM, or a combined IN+IM vaccination inhealthy adults previously immunized against COVID-19. The IN and IM live virusvaccinations will be identical in composition and only differ in route of administration.
Primary Study Objective: To evaluate the safety and tolerability profile of two dose
levels of the NDV-HXP-S vaccine as an IN, IM, or a combined administration IN+IM to
healthy, previously immunized adults up to 14 days after administration.
Secondary Study Objective: To evaluate the safety and tolerability profile of two dose
levels of the NDV-HXP-S vaccine as an IN, IM, or a combined administration IN+IM to
healthy, previously immunized adults up to 365 days after administration.
Drug: Sodium Chloride
Administered intranasal (IN) and intramuscular (IM) in combination
Other Name: Placebo
Biological: NDV-HXP-S IN low dose
Allantoic fluid diluted in Phosphate buffered saline (PBS), to be further diluted to dose
strength in sodium chloride.
Strength: 3.3x108^8 EID50.
Biological: NDV-HXP-S IM low dose
Allantoic fluid diluted in Phosphate buffered saline (PBS), to be further diluted to dose
strength in sodium chloride.
Strength: 3.3x10^8 EID50.
Biological: NDV-HXP-S IN high dose
Allantoic fluid diluted in Phosphate buffered saline (PBS). Strength: 1x10^9 EID50.
Biological: NDV-HXP-S IM high dose
Allantoic fluid diluted in Phosphate buffered saline (PBS). Strength: 1x10^9 EID50.
Inclusion Criteria:
1. Willing and able to provide written informed consent prior to performing study
procedures.
2. Males and non-pregnant females who are between 18 to 59 years of age.
3. Asymptomatic, RT-PCR negative (at screening) AND without a known prior history of
COVID-19 infection (requiring a negative SARS-CoV-2 nucleocapsid antibody test
result at screening).
4. Provides documentation showing completion of an FDA authorized or approved COVID-19
vaccination regimen, where the last administration was ≥ 6 months (180 days) from
the study enrollment date.
5. IF FEMALE PARTICIPANT: A female participant is eligible to participate if she is not
pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a woman of child-bearing potential (WOCBP); OR
- Is a WOCBP and using an acceptable contraceptive method during the intervention
period (for a minimum of 90 days after NDV-HXP-S vaccination). The investigator
should evaluate the effectiveness of the contraceptive method in relationship
to the first dose of study intervention. Only highly effective methods of
contraception that have a low user dependency or a combination of highly
effective methods that are user dependent may be used.
6. IF MALE PARTICIPANT: Agrees to the following requirements during the intervention
period and for at least 90 days after NDV-HXP-S vaccination, which corresponds to
the time needed to eliminate reproductive safety risk of the study intervention(s):
- Refrain from donating sperm AND be abstinent from heterosexual intercourse with
a female of childbearing potential as their preferred and usual lifestyle
(abstinent on a long-term and persistent basis) and agree to remain abstinent;
OR
- Must agree to use a male condom when engaging in any activity that allows for
passage of ejaculate to another person. In addition to male condom use, a
highly effective method of contraception may be considered in WOCBP partners of
male participants.
7. Participant understands and agrees to comply with planned study procedures.
8. Participant agrees to not participate in another clinical trial for treatment of
COVID-19 or SARS-CoV-2 through Day 365.
9. Participant agrees to not receive any other vaccination (including COVID-19
vaccines) through day 56 of the study.
10. Provides consent for release of information for hospitalization records and other
medically attended visits during the study.
Exclusion Criteria:
1. Clinical and/or laboratory evidence indicative of COVID-19 infection.
2. Demonstrates a STRONG COVID-19 positive antibody serology (>12500 AU/ml per
chemiluminescent microparticle immunoassay (including AdviseDx SARS-CoV-2 IgG II))
or a NEGATIVE COVID-19 serology on screening against SARS-CoV-2 spike protein.
3. History of hypersensitivity to egg products.
4. History of severe reactions to vaccinations.
5. Potential for prior NDV exposures (i.e., experience as a bird-handler, poultry
farmer, or scientist conducting research with NDV).
6. History of an immunocompromising medical condition (such as primary
immunodeficiencies, AIDS, or neutropenia).
7. Current or recent use of immunosuppressive medications (i.e., any systemic
corticosteroids, chemotherapeutics, immunoglobulin therapies, etc.) based on the
assessment of their half-life by the investigator.
8. Any history of HIV, hepatitis C, hepatitis B (by laboratory testing and/or history),
Guillain-Barré syndrome, and/or recent receipt of immunoglobulins and/or blood
products.
9. Pregnancy or actively breastfeeding.
10. Other medical condition or abnormal laboratory values which may place participant at
increased risk for harm due to participation in the study as determined by the
investigator.
11. In the opinion of the investigator that it would be unwise to allow the participant
to be randomized into the study, including those persons who the investigator would
consider as high risk of SARS-CoV-2 exposure, including healthcare workers with
direct patient care and laboratory workers who handle SARS-CoV-2.
12. Participants at higher risk of severe COVID-19, as defined by CDC guidance
(https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/index…), where
severity of risk and eligibility will be determined by the investigator. This
guidance includes details regarding older adults, people with specific medical
conditions, and pregnant and recently pregnant people.
13. Participants with fever or signs of acute infection, including symptoms that could
indicate SARS-CoV-2 infection.
14. Participants with a history of chronic rhinitis, nasal septal defect, cleft palate,
nasal polyps, or other nasal abnormality that might affect vaccine administration.
15. Participants who prepare food in the food industry and childcare workers who have
direct contact with children 5 years of age or younger.
16. Participants who have close or household high-risk contacts including but not
limited to:
- Persons more than or equal to 65 years of age
- Children less than or equal to 5 years of age.
- Residents of nursing homes.
- Persons of any age with significant chronic medical conditions as well as
immunosuppression or cancer.
Women who are pregnant, trying to become pregnant, or breastfeeding.
17. Participants who are students, post-doctoral candidates, or trainees of the study
site, or are members of the research staff.
18. Participants with a history of myocarditis or pericarditis and individuals with an
abnormal troponin or abnormal ECG as determined by the investigator. Participants
with a screening 12-lead ECG that shows an average QTc interval >500 msec, complete
left bundle branch block, ST-T interval changes suggestive of myocardial ischemia,
second- or third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias
should be excluded from study participation.
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Sean Liu, MD, PhD, Principal Investigator
Icahn School of Medicine at Mount Sinai