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 study sites will be assigned to enroll either only participants who will receive IM administration (up to 5 sites) or only participants who will receive IN administration (up to 5 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.
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 study sites will be assigned to enroll either only participants who will receive IM administration (up to 5 sites) or only participants who will receive IN administration (up to 5 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
140
Aluminum hydroxide adjuvant.
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.
CPG 7909 is a synthetic oligodeoxynucleotide used as an adjuvant.
0.9% Sodium Chloride Injection
University of California San Francisco - Zuckerberg San Francisco General Hospital - Division of Human Immunodeficiency Virus, Infectious Disease, and Global Medicine
San Francisco, California, United States
Center for Immunization Research, Johns Hopkins Bloomberg School Public Health
Baltimore, Maryland, United States
Saint Louis University Center for Vaccine Development
St Louis, Missouri, United States
University of Rochester Medical Center - Vaccine Research Unit
Rochester, New York, United States
Duke Vaccine and Trials Unit
Durham, North Carolina, United States
University of Pittsburgh - Medicine - Infectious Diseases
Pittsburgh, Pennsylvania, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Kaiser Permanente Washington Health Research Institute
Seattle, Washington, United States
Occurrence of abnormal clinical safety laboratory adverse events.
Time frame: Through day 8
Occurrence of adverse events of special interest (AESIs).
Time frame: Through 6 months
Occurrence of medically attended adverse events (MAAEs).
Time frame: Through 6 months
Occurrence of new onset chronic medical conditions (NOCMCs).
Time frame: Through 6 months
Occurrence of potentially immune-mediated diseases (pIMDs)
Time frame: Through 6 months
Occurrence of Serious adverse events (SAEs).
Time frame: Through 6 months
Occurrence of solicited local adverse events (AEs).
Time frame: Through 7 days
Occurrence of solicited systemic adverse events (AEs).
Time frame: Through 7 days
Occurrence of unsolicited adverse events (AEs).
Time frame: Through 28 days
Geometric mean (GM) of nasal mucosal anti-S binding Immunoglobulin A (IgA) antibodies.
Time frame: Day 1 through 181
Geometric mean (GM) of nasal mucosal anti-S binding Immunoglobulin G (IgG) antibodies.
Time frame: Day 1 through 181
Geometric mean (GM) of serum anti-spike binding Immunoglobulin A antibodies (IgA).
Time frame: Days 1 through 181
Geometric mean (GM) of serum anti-spike binding Immunoglobulin G antibodies (IgG).
Time frame: Days 1 through 181
Geometric mean fold rise (GMFR) from baseline of anti-spike serum neutralizing antibodies to spike variants
Time frame: Days 1 through 181
Geometric mean fold rise (GMFR) from baseline of nasal mucosal anti-S binding Immunoglobulin A (IgA) antibodies.
Time frame: Day 1 through 181
Geometric mean fold rise (GMFR) from baseline of nasal mucosal anti-S binding Immunoglobulin G (IgG) antibodies.
Time frame: Day 1 through 181
Geometric mean fold rise (GMFR) from baseline of serum anti-spike Immunoglobulin A antibodies (IgA).
Time frame: Days 1 through 181
Geometric mean fold rise (GMFR) from baseline of serum anti-spike Immunoglobulin G antibodies (IgG).
Time frame: Days 1 through 181
Geometric mean of anti-spike serum-neutralizing antibodies to spike variants
Time frame: Days 1 through 181
Seroconversion rate
Where seroconversion is defined as at least a 4-fold increase in serum neutralizing antibody titers over baseline.
Time frame: Days 29
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