Campylobacter Infection
Conditions
Keywords
ALFQ, Campylobacter jejuni, Campylobacter jejuni Conjugate Vaccine, CJCV2, Immunogenicity, QS-21, safety
Brief summary
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.
Detailed description
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.
Interventions
DRUGALFQ
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.
BIOLOGICALCJCV2
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.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provide informed consent prior to initiation of any study procedures. 2. Able to understand and comply with planned study procedures and be available for all study visits/safety communications. 3. Non-pregnant/non-lactating subjects 18-50 years of age inclusive upon enrollment. 4. In general, good health\* to be safely enrolled in this study as determined by medical history, medication use\*\*, and physical exam. \*Good health is defined by the absence of any exclusionary medical conditions. If the subject has another current, ongoing medical condition, the condition cannot meet any of the following criteria; 1) first diagnosed within 3 months of enrollment; 2) is worsening in terms of clinical outcome in last 6 months; or 3) involves need for medication that may pose a risk to subject's safety or impede assessment of AEs or immunogenicity if they participate in the study. \*\*Topical, nasal, and inhaled medications (with the exception of inhaled corticosteroids as outlined in the Subject Exclusion #17). Herbals, vitamins, and supplements are permitted. 5. Oral temperature is less than 100.4 degrees F. 6. Pulse is 50 to 100 beats per minute (bpm), inclusive. 7. Systolic blood pressure (BP) is 90 to 140 mmHg, inclusive. 8. Diastolic BP is 55 to 90 mmHg, inclusive. 9. Body Mass Index(BMI) less than 40. 10. Females of childbearing potential\* may enroll if subject has practiced adequate contraception\*\* \> 30 days prior to enrollment and agrees to continue adequate contraception for the entire study. \*Child-bearing potential is defined as not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure (R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or \<1 year of the last menses if menopausal. \*\*Adequate contraception includes; non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving the first study vaccination, barrier methods such as condoms or diaphragms with spermicide, effective intrauterine devices, NuvaRing (R), and licensed hormonal methods such as implants, injectables, or oral contraceptives ("the pill"). 11. Females of childbearing potential must have a negative urine pregnancy test within 24 hours prior to enrollment. 12. Agree not to participate in another interventional clinical trial during the study period that may affect the analysis or endpoint assessment. 13. Negative urine drug screen for opiates.
Exclusion criteria
1. Have any disease or medical condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation\*. \*Including acute or chronic disease or medical condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial. These include: History of inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, indeterminate colitis, or celiac disease). Within the past 12 months, has any of the following: irritable bowel syndrome (IBS) or any active uncontrolled gastrointestinal disorders or diseases as assessed by the investigator, including symptoms or evidence of active gastritis or gastroesophageal reflux disease, gastric surgery or gastric acid hyper-secretory disorders (e.g., Zollinger-Ellison syndrome), gastrointestinal obstruction, ileus, gastric retention, bowel perforation, toxic colitis, persistent infectious gastroenteritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection. History of immunodeficiency due to congenital or hereditary causes, underlying illness or treatment, autoimmune disorders, or chronic inflammatory disorders. History of an inflammatory arthritis such as reactive arthritis, Reiter's syndrome, ankylosing spondylitis, rheumatoid arthritis, or GBS. Known active neoplastic disease non-melanoma, treated, skin cancers are permitted, a history of any hematologic malignancy, or have used anticancer chemotherapy/radiation therapy (cytotoxic) within 5 years prior to study vaccination. Other condition requiring daily therapy that would place the volunteer at increased risk or Adverse Events (AE). Other laboratory abnormalities which in the opinion of the investigator precludes participation in the study. Clinically significant abnormalities on physical exam. 2. Documented history of auto-immune conditions in a first-degree relative. Examples include reactive arthritis, Reiter's syndrome, ankylosing spondylitis, rheumatoid arthritis, or GBS. 3. History of Potentially Immune-Mediated Medical Conditions (PIMMCs). 4. Evidence of inflammatory arthritis on exam and/or positive serology results for HLA-B27. 5. Positive Human Immunodeficiency Virus (HIV), Hepatitis B Surface Antigen (HBsAg), or Hepatitis C antibodies (HCVs). 6. Participation in a previous Campylobacter study or reports having received vaccination against Campylobacter within the last 3 years. 7. History of microbiologically confirmed Campylobacter infection in the last 3 years. 8. Occupation involving handling of Campylobacter bacteria or vaccine products currently or in the past 3 years. 9. Use of immunosuppressive/immunomodulating disease therapy within 90 days 10. Received Immunoglobulin (Ig) or other blood products (with exception of Rho D Ig) within 90 days prior to enrollment. 11. Have a history of severe reactions following previous immunization with any licensed or unlicensed vaccine. 12. Known hypersensitivity to any components of vaccine, adjuvant or diluent. 13. Received or plan to receive a licensed live vaccine within 30 days prior to 1st vaccination and to 30 days after the last vaccination. 14. Received or plan to receive a licensed, inactivated, vaccine within 14 days prior to 1st vaccination to 14 days after the last vaccination, or a seasonal influenza and/or COVID-19 vaccine +/- 7 days from study product vaccination. 15. Individuals in whom the ability to observe possible local reactions at the eligible injection sites (deltoid region) is unacceptably obscured due to a physical condition or permanent body art. 16. Within 14 days prior to vaccination has received an oral or parenteral (including intra-articular) corticosteroid of any dose for 5 or more days, or high-dose inhaled corticosteroids. a) High dose defined per age as using inhaled high dose per reference chart (https://www.nhlbi.nih.gov/files/docs/guidelines/asthma\_qrg.pdf) 17. Current or history of alcohol or drug abuse within one year prior to enrollment. 18. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations. 19. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within one year prior to enrollment. 20. Are pregnant, breastfeeding, or plan to become pregnant or breastfeed at any given time during the study. 21. Have an acute illness as determined by study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as the site PI or sub-investigator, within 72 hours prior to enrollment. a. An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as the site PI or sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol. 22. Received an investigational product within 30 days prior to the first study vaccination or expect to receive an investigational product during the study period. a. Including vaccine, drug, biologic, device, blood product, or medication, other than from participation in this trial. 23. Have abnormal screening laboratory values within 30 days prior to enrollment. a. Screening laboratory values that are outside acceptable range but are thought to be due to an acute condition or due to laboratory error may be repeated once.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Participants With Solicited Local Adverse Events (AEs) Through 7 Days After Each Study Vaccination | Days 1 through 8, Days 29 through 36, and Days 57 through 64 | 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. |
| Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination | Days 1 through 8, Days 29 through 36, and Days 57 through 64 | 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. |
| Number and Percentage of Participants With Vaccine-related Unsolicited AEs Through 28 Days Post Last Vaccination | Day 1 through Day 85 | 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. |
| Number and Percentage of Participants With Serious Adverse Events (SAEs) | Day 1 through Day 420 | 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. |
| Number and Percentage of Participants With Medically Attended Adverse Events (MAAEs) From First Study Vaccination Through End of Study Participation | Day 1 through Day 420 | 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. |
| Number and Percentage of Participants With New-onset Chronic Medical Conditions (NOCMCs) From First Study Vaccination Through End of Study Participation | Day 1 through Day 420 | 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. |
| Number and Percentage of Participants With Potentially Immune-mediated Medical Conditions (PIMMCs) From First Study Vaccination Through End of Study Participation | Day 1 through Day 420 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With >= 4-fold Rise From Baseline in C. Jejuni Capsule-specific Immunoglobulin G (IgG) Serum Antibodies | Days 8, 29, 36, 57, 64, 85, and 113 | 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. |
| Peak Fold Rise From Baseline in C. Jejuni Capsule-specific Immunoglobulin G (IgG) Serum Antibody Titer | Day 8 through Day 113 | 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. |
| Maximum C. Jejuni Capsule-specific Immunoglobulin G (IgG) Serum Antibody Titer | Day 8 through Day 113 | 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. |
Countries
United States
Participant flow
Recruitment details
The study population was comprised of generally healthy young adults (males and non-pregnant or -lactating females) 18-50 years of age, inclusive, who met all eligibility criteria. Participants were recruited from existing volunteer populations and from the communities at large around the clinical site. Fifty-nine participants were enrolled between 13Sep2022 and 08Nov2023.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 31.8 years STANDARD_DEVIATION 6.9 |
| Body Mass Index | 29.04 kg/m^2 STANDARD_DEVIATION 5.49 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 171.60 cm STANDARD_DEVIATION 7.96 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 59 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
| Weight | 81.10 kg STANDARD_DEVIATION 19.11 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 9 | 0 / 10 |
| other Total, other adverse events | 10 / 10 | 10 / 10 | 9 / 10 | 10 / 10 | 9 / 9 | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 1 / 10 | 0 / 9 | 1 / 10 |
Outcome results
None listed