This is a randomized, double-blind, dose-escalating, outpatient trial in a total of approximately 60 subjects, assigned to 3 cohorts (20 subjects per cohort). Each subject will receive one of three intramuscular (IM) vaccinations, spaced 28 days apart, of Campylobacter jejuni Conjugate Vaccine (CJCV2) with or without a fixed dose of the adjuvant Army Liposome Formulation containing QS-21 (ALFQ)(200 mcg 3D-PHAD, 100 mcg QS-21). Three doses (1 ug, 3 ug and 10 ug) of CJCV2 will be evaluated. The first six participants at each dose will be sentinels and randomized in a 1:1 blinded fashion to receive CJCV2 with or without ALFQ. The primary objective is to evaluate the safety of the three different doses of IM injection of CJCV2 with and without ALFQ. The study hypothesis is that the CJCV2 vaccine alone and CJCV2 with ALFQ adjuvant will be safe and that the CJCV2 alone will be immunogenic, with immunogenicity enhanced through the use of the adjuvant ALFQ.
This is a randomized, double-blind, dose-escalating, outpatient trial in a total of approximately 60 subjects, assigned to 3 cohorts (20 subjects per cohort). Each subject will receive one of three intramuscular (IM) vaccinations, spaced 28 days apart, of Campylobacter jejuni Conjugate Vaccine (CJCV2) with or without a fixed dose of the adjuvant Army Liposome Formulation containing QS-21 (ALFQ)(200 mcg 3D-PHAD, 100 mcg QS-21).Three doses (1 ug, 3 ug and 10 ug) of CJCV2 will be evaluated. The first six participants at each dose will be sentinels and randomized in a 1:1 blinded fashion to receive CJCV2 with or without ALFQ. The primary objective is to evaluate the safety of the three different doses of IM injection of CJCV2 with and without ALFQ. The secondary objective is to evaluate C. jejuni capsule-specific serum IgG responses following vaccination. The study hypothesis is that the CJCV2 vaccine alone and CJCV2 with ALFQ adjuvant will be safe and that the CJCV2 alone will be immunogenic, with immunogenicity enhanced through the use of the adjuvant ALFQ.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
59
ALFQ (Army Liposome Formulation containing QS-21) is composed of ALF55 (cGMP-manufactured Army Liposome Formulation), QS-21 (purified extracted saponin), and Sorensen's Phosphate Buffer. Full dose of AFLQ compromised of 200 microgram 3D-PHAD and 100 microgram QS-21, co-administered with main intervention.
Vaccine comprised of C. jejuni capsule conjugated to Cross-Reactive Material 197 (CRM197), a non-toxic mutant protein of diphtheria toxin. CJCV2 will be reconstituted in 1 mL of sterile water for injection (SWI). The resuspended CJCV2 product will be diluted with sterile 0.9% Sodium Chloride for Injection. 3 dosages for administration: 1 microgram, 3 micrograms, and 10 micrograms.
Cincinnati Children's Hospital Medical Center Vaccine Research Center
Cincinnati, Ohio, United States
Number and Percentage of Participants With Solicited Local Adverse Events (AEs) Through 7 Days After Each Study Vaccination
Solicited local AEs were collected 30 minutes post-vaccination, and then daily for 7 days after each vaccination using a memory aid and graded on a scale of 0 (none), 1 (mild), 2 (moderate) and 3 (severe). Local symptoms included ecchymosis, ecchymosis (measurement), erythema, erythema (measurement), induration/edema, induration/edema (measurement), pain, and tenderness.
Time frame: Days 1 through 8, Days 29 through 36, and Days 57 through 64
Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination
Solicited systemic AEs were collected prior to vaccination, 30 minutes post-vaccination, and then daily for 7 days after each vaccination using a memory aid and graded on a scale of 0 (none), 1 (mild), 2 (moderate) and 3 (severe). Systemic symptoms included arthralgia, fatigue, fever, feverishness (chills/shivering/sweating), headache, malaise, myalgia, nausea, and vomiting.
Time frame: Days 1 through 8, Days 29 through 36, and Days 57 through 64
Number and Percentage of Participants With Vaccine-related Unsolicited AEs Through 28 Days Post Last Vaccination
ICH E6 defines an AE as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, regardless of its causal relationship to the study treatment. The FDA defines an AE as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. The occurrence of an AE could have come to the attention of study personnel during study visits and interviews of a study participant presenting for medical care, or upon review by a study monitor. An AE was considered related if there was a reasonable possibility that the study product caused the AE. Reasonable possibility means that there was evidence to suggest a causal relationship between the study product and the AE.
Time frame: Day 1 through Day 85
Number and Percentage of Participants With Serious Adverse Events (SAEs)
An AE or suspected adverse reaction was considered a SAE if, in the view of either the PI or sponsor, it resulted in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not have resulted in these outcomes could be considered serious when, based upon appropriate medical judgment, they could have jeopardized the participant and could have required medical or surgical intervention to prevent one of the outcomes listed in this definition.
Time frame: Day 1 through Day 420
Number and Percentage of Participants With Medically Attended Adverse Events (MAAEs) From First Study Vaccination Through End of Study Participation
Medically attended adverse events (MAAEs) are any unsolicited AE for which a participant received medical attention, defined as hospitalization, an ER visit, or an otherwise unscheduled visit to or from medical personnel.
Time frame: Day 1 through Day 420
Number and Percentage of Participants With New-onset Chronic Medical Conditions (NOCMCs) From First Study Vaccination Through End of Study Participation
New-onset chronic medical conditions (NOCMCs) are defined as any new ICD-10 diagnosis that is applied to the participant during the duration of the study, after receipt of the study product, that is expected to continue for at least 3 months and requires continued health care intervention.
Time frame: Day 1 through Day 420
Number and Percentage of Participants With Potentially Immune-mediated Medical Conditions (PIMMCs) From First Study Vaccination Through End of Study Participation
Potentially immune-mediated medical conditions (PIMMCs) constitute a group of AEs that includes diseases which are clearly autoimmune in etiology and other inflammatory and/or neurologic disorders which may or may not have autoimmune etiologies.
Time frame: Day 1 through Day 420
Percentage of Participants With >= 4-fold Rise From Baseline in C. Jejuni Capsule-specific Immunoglobulin G (IgG) Serum Antibodies
Serum from blood collected at Study Days 1, 8, 29, 36, 57, 64, 85, and 113 was analyzed using an enzyme-linked immunosorbent assay (ELISA) to measure C. jejuni capsule-specific Immunoglobulin G (IgG) serum antibody titers. Results below the lower limit of quantification (LLOQ) were imputed as LLOQ/2. The percentage of participants with at least a 4-fold rise in antibody titer compared to pre-vaccination 1 is presented by arm with exact 95% Clopper-Pearson confidence interval.
Time frame: Days 8, 29, 36, 57, 64, 85, and 113
Peak Fold Rise From Baseline in C. Jejuni Capsule-specific Immunoglobulin G (IgG) Serum Antibody Titer
Serum from blood collected at Study Days 1, 8, 29, 36, 57, 64, 85, and 113 was analyzed using an enzyme-linked immunosorbent assay (ELISA) to measure C. jejuni capsule-specific Immunoglobulin G (IgG) serum antibody titers. Results below the lower limit of quantification (LLOQ) were imputed as LLOQ/2. For each participant, peak fold-rise from baseline is defined as the maximum fold-rise in antibody titer that occurred throughout all follow-up visits with available data (Day 8 up to Day 113) as compared to baseline (Day 1). The peak fold-rise from baseline per participant is summarized by study arm via geometric mean and 95% confidence interval based on Student's t distribution.
Time frame: Day 8 through Day 113
Maximum C. Jejuni Capsule-specific Immunoglobulin G (IgG) Serum Antibody Titer
Serum from blood collected at Study Days 1, 8, 29, 36, 57, 64, 85, and 113 was analyzed using an enzyme-linked immunosorbent assay (ELISA) to measure C. jejuni capsule-specific Immunoglobulin G (IgG) serum antibody titers. Results below the lower limit of quantification (LLOQ) were imputed as LLOQ/2. For each participant, the maximum antibody titer measured throughout all follow-up visits with available data (Day 8 up to Day 113) was recorded. The maximum post-baseline titer per participant is summarized by study arm via geometric mean and 95% confidence interval based on Student's t distribution.
Time frame: Day 8 through Day 113
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