This phase 1 clinical trial will evaluate the safety, reactogenicity, and immunogenicityof Boost-2867, given intramuscular (IM) with or without adjuvant or intranasal (IN)without adjuvant, as a booster dose to previously vaccinated healthy adults. Each of thesix study sites will be assigned to enroll either only participants who will receive IMadministration (3 sites) or only participants who will receive IN administration (3sites); no site will administer both IM and IN study product administrations. Within theIM and IN Arms the cohorts will be sequentially enrolled. The study is designed as anon-randomized, open-label, dose-escalation clinical trial evaluating one dose level ofBoost-2867 without adjuvant administered IM, three dose levels of Boost-2867 withadjuvant administered IM, and three dose levels of Boost-2867 without adjuvantadministered IN. A sample size of 140 participants (20 participants per dose cohort) isanticipated. To evaluate for early safety signals for this first-in-human trial, studyproduct administration of participants enrolled for IM administration and those enrolledfor IN administration will proceed in a staged fashion. For Cohorts 1 (IM administrationwithout adjuvant) and 5 (IN administration), which may be enrolled and dosedconcurrently, 3 sentinel participants under 50 years of age will be enrolled in eachCohort over at least 2 days. For each of those Cohorts independently, a safety review ofhalting rules and clinical safety data through at least Day 8 will be conducted by theProtocol Safety Review Team (PSRT) prior to enrollment of the remainder of the cohort.Enrollment, dosing, and safety oversight for IM Cohorts 2, 3, and 4 will proceed in thesame fashion as Cohort 1, except that sentinel enrollment need not be spaced over atleast 2 days. Similarly, for IN Cohorts 6 and 7, enrollment and safety oversight willproceed in the same fashion as Cohort 5, except that sentinel enrollment need not bespaced over at least 2 days.The primary objectives are: 1) To evaluate the safety and reactogenicity of a single IMinjection of three different antigen dose levels (5, 15, and 50 microgram) of Boost-2867with Alhydrogel (R) (alum) and CpG 7909 adjuvants, and a single injection of 50 microgramBoost-2867 without adjuvant, in previously vaccinated healthy adults. 2) To evaluate thesafety and reactogenicity of a single IN administration of three different antigen doselevels (20, 50, and 125 microgram) of Boost-2867 without adjuvant in previouslyvaccinated healthy adults.
This phase 1 clinical trial will evaluate the safety, reactogenicity, and immunogenicity
of Boost-2867, given intramuscular (IM) with or without adjuvant or intranasal (IN)
without adjuvant, as a booster dose to previously vaccinated healthy adults. Each of the
six study sites will be assigned to enroll either only participants who will receive IM
administration (3 sites) or only participants who will receive IN administration (3
sites); no site will administer both IM and IN study product administrations. Within the
IM and IN Arms the cohorts will be sequentially enrolled. The study is designed as a
non-randomized, open-label, dose-escalation clinical trial evaluating one dose level of
Boost-2867 without adjuvant administered IM, three dose levels of Boost-2867 with
adjuvant administered IM, and three dose levels of Boost-2867 without adjuvant
administered IN. A sample size of 140 participants (20 participants per dose cohort) is
anticipated. To evaluate for early safety signals for this first-in-human trial, study
product administration of participants enrolled for IM administration and those enrolled
for IN administration will proceed in a staged fashion. For Cohorts 1 (IM administration
without adjuvant) and 5 (IN administration), which may be enrolled and dosed
concurrently, 3 sentinel participants under 50 years of age will be enrolled in each
Cohort over at least 2 days. For each of those Cohorts independently, a safety review of
halting rules and clinical safety data through at least Day 8 will be conducted by the
Protocol Safety Review Team (PSRT) prior to enrollment of the remainder of the cohort.
Enrollment, dosing, and safety oversight for IM Cohorts 2, 3, and 4 will proceed in the
same fashion as Cohort 1, except that sentinel enrollment need not be spaced over at
least 2 days. Similarly, for IN Cohorts 6 and 7, enrollment and safety oversight will
proceed in the same fashion as Cohort 5, except that sentinel enrollment need not be
spaced over at least 2 days. The primary objectives are: 1) To evaluate the safety and
reactogenicity of a single IM injection of three different antigen dose levels (5, 15,
and 50 microgram) of Boost-2867 with Alhydrogel (R) (alum) and CpG 7909 adjuvants, and a
single injection of 50 microgram Boost-2867 without adjuvant, in previously vaccinated
healthy adults. 2) To evaluate the safety and reactogenicity of a single IN
administration of three different antigen dose levels (20, 50, and 125 microgram) of
Boost-2867 without adjuvant in previously vaccinated healthy adults. The secondary
objectives are: 1) To evaluate the systemic anti-Spike humoral immune responses of a
single IM or IN administration of Boost-2867. 2) To evaluate nasal mucosal immunoglobulin
A (IgA) and immunoglobulin G (IgG) responses after IM and IN administration.
Drug: Aluminum Hydroxide Suspension
Aluminum hydroxide adjuvant.
Biological: Boost-2867
Boost-2867 is a recombinant ~50 kDa SARS-CoV-2 RBD (KP.2 variant) S1 subunit joined to a
human IgG1 Fc, forming a ~100 kDa homodimer.
Biological: CpG 7909
CPG 7909 is a synthetic oligodeoxynucleotide used as an adjuvant.
Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection
Inclusion Criteria:
1. Provides written informed consent before initiation of any study procedures.
2. Able to understand and agree to comply with planned study procedures and be
available for all study visits.
3. Non-pregnant adults, 18 through 64 years of age at the time of study product
administration.
4. Participants of childbearing potential* must agree to use or have practiced true
abstinence** or use at least one acceptable primary form of contraception***.
- These criteria apply to females who are in a heterosexual relationship who are
of childbearing potential. Not of childbearing potential include
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 tubal ligation/salpingectomy).
- True abstinence is 100% of the time, no sexual intercourse (penis enters
the vagina). Periodic abstinence (e.g., calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods.
- Acceptable forms of primary contraception include a monogamous
relationship with a vasectomized partner who has been vasectomized
for 180 days or more before the participant's study product
administration, 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 before study product
administration and agree to continue at least one acceptable primary
form of contraception through 60 days after study product
administration.
5. Participants of childbearing potential must have a negative urine pregnancy test at
screening and within 24 hours before study product administration.
6. In general good 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 the safety of participants. Chronic medical diagnoses/ conditions
should be stable for the last 30 days (i.e., no hospitalizations, ER, or urgent care
for the condition). This includes no change in chronic prescription medication,
dose, or frequency due to deterioration of the chronic medical diagnosis/condition
30 days before the study product administration. Any prescription change due to a
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.
7. Receipt of a complete primary authorized or approved COVID-19 vaccine series and at
least one booster*.
* Booster may be either homologous or heterologous to the primary vaccine series. It
must be an FDA-authorized/licensed vaccine, though doses may have been received
during a clinical trial.
8. Clinical screening laboratory evaluations are within normal reference ranges or
grade 1 with no clinical significance (NCS) per the investigator's discretion*.
*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). Alanine Transaminase (ALT), Aspartate
Transaminase (AST), Alkaline Phosphatase (ALP), Total Bilirubin (T. Bili), and
creatinine values below the reference range will not be exclusionary as these values
below the reference range are clinically insignificant.
9. 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):
*Grade 1 or higher is equivalent to: Systolic blood pressure (SBP) >/= 141 mmHg or
/= 91 mmHg Heart rate (HR) is >/= 101
beats per minute or /= 38.0 degrees
Celsius (100.4 degrees Fahrenheit)
3. Self-reported or medically documented SARS-CoV-2 infection (regardless of whether
symptomatic or asymptomatic) within 16 weeks prior to study product administration.
4. Participant who is pregnant or breastfeeding.
5. Blood or plasma donation within 4 weeks before study product administration.
6. Receipt of antibody or blood-derived products within 90 days before study product
administration.
7. Any self-reported or documented significant medical or psychiatric diseases* or any
other condition that, in the opinion of the site PI or appropriate sub-investigator,
precludes study participation.
*Significant medical or psychiatric conditions include but are not limited to drug
or alcohol abuse within 6 months of enrollment, significant kidney disease, liver
disease, ongoing malignancy, or recent diagnosis of malignancy in the last five
years, excluding treated basal and squamous cell carcinoma of the skin and cervical
carcinoma in situ, which are allowed.
8. Neurological or neurodevelopmental conditions*.
*Including 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.
9. History of significant respiratory disease currently requiring daily medications,
history of asthma in the past 5 years, or any treatment of respiratory disease
exacerbations in the last 5 years.
10. History of cardiovascular disease (e.g., congestive heart failure, cardiomyopathy,
ischemic heart disease), including any history of myocarditis, pericarditis, or
uncontrolled cardiac arrhythmia.
11. Any autoimmune disease, including hypothyroidism, without a defined non-autoimmune
cause.
12. Has an acute illness determined by the site PI or appropriate sub-investigator
within 72 hours before study product administration*.
*An acute illness that is nearly resolved with only minor residual symptoms
remaining is allowable if, in the opinion of the participating site PI or
appropriate sub-investigator, the residual symptoms will not interfere with the
ability to assess safety parameters as required by the protocol.
13. Has a positive test result for hepatitis B surface antigen, hepatitis C virus RNA
(by reflex testing), or human immunodeficiency virus (HIV) antigen/antibody test at
screening.
14. 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 means more than 14 continuous days.
**Ophthalmic and topical steroids are allowed.
15. Has received any investigational study product within 60 days, or 5 half-lives,
whichever is longer, before study product administration or is planning to receive
one during the study.
16. Has a history of hypersensitivity or severe allergic reaction* to any previous
licensed or unlicensed study products or the candidate study product components**.
*(e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction)
**See IB for study product formulation.
17. Received or plans to receive licensed inactivated/subunit vaccine within 14 days of
study product administration or live vaccine within 28 days of study product
administration.
18. Plan to receive a COVID-19 booster vaccine within the 180 days following study
product administration.
19. Regular use of intranasal medications, including steroids, and sinus rinsing
treatments*.
*Participants must have had no intranasal medication use for 30 days before study
product administration and do not plan to use intranasal medications for 30 days
after study product administration for medications other than steroids and for 6
months after study product administration for intranasal steroids (including
over-the-counter (OTC) fluticasone).Participants should not use nasal irrigation or
sinus rinsing treatments (e.g., Neti pots or saline washes) for 28 days after the
study product administration and 7 days before study visits for the duration of the
trial.
20. Use of illicit intranasal drugs in the 5 years before study product administration
or plans to use during the study.
21. Current smoker (including cigarettes, marijuana, and vaping) or smoking within the
prior 3 months.
22. Planned international travel between product administration and Day 29 visit.
23. Any significant nasal or upper airway disease*. *Including, but not limited to,
being prone to epistaxis, has a history of inflammatory rhinitis (including allergic
rhinitis) that requires daily medications, cochlear implants, head/neck radiation
history, anosmia/dysosmia, and certain ear, nose and throat (ENT) conditions,
including major anatomic nasopharyngeal abnormality or sinus polyp disease due to
chronic sinusitis.
Not Provided
Lisa A. Jackson
12062874267
lisa.a.jackson@kp.org
Not Provided