Safety and Immunogenicity of CJCV2 With and Without ALFQ

Study Overview
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Brief Summary
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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
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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.

Official Title
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First-in-Human Safety and Immunogenicity Evaluation of an Intramuscular Campylobacter Jejuni Conjugate Vaccine (CJCV2) With and Without Army Liposome Formulation Containing QS-21 (ALFQ)

Conditions
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Campylobacter Infection

Intervention / Treatment
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* Drug: ALFQ
* Biological: CJCV2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide informed consent prior to initiation of any study procedures. Able to understand and comply with planned study procedures and be available for all study visits/safety communications. Non-pregnant/non-lactating subjects 18-50 years of age inclusive upon enrollment. 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. Oral temperature is less than 100.4 degrees F. Pulse is 50 to 100 beats per minute (bpm), inclusive. Systolic blood pressure (BP) is 90 to 140 mmHg, inclusive. Diastolic BP is 55 to 90 mmHg, inclusive. Body Mass Index(BMI) less than 40. 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). Females of childbearing potential must have a negative urine pregnancy test within 24 hours prior to enrollment. Agree not to participate in another interventional clinical trial during the study period that may affect the analysis or endpoint assessment. Negative urine drug screen for opiates. Exclusion Criteria: 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. Documented history of auto-immune conditions in a first-degree relative. Examples include reactive arthritis, Reiter's syndrome, ankylosing spondylitis, rheumatoid arthritis, or GBS. History of Potentially Immune-Mediated Medical Conditions (PIMMCs). Evidence of inflammatory arthritis on exam and/or positive serology results for HLA-B27. Positive Human Immunodeficiency Virus (HIV), Hepatitis B Surface Antigen (HBsAg), or Hepatitis C antibodies (HCVs). Participation in a previous Campylobacter study or reports having received vaccination against Campylobacter within the last 3 years. History of microbiologically confirmed Campylobacter infection in the last 3 years. Occupation involving handling of Campylobacter bacteria or vaccine products currently or in the past 3 years. Use of immunosuppressive/immunomodulating disease therapy within 90 days Received Immunoglobulin (Ig) or other blood products (with exception of Rho D Ig) within 90 days prior to enrollment. Have a history of severe reactions following previous immunization with any licensed or unlicensed vaccine. Known hypersensitivity to any components of vaccine, adjuvant or diluent. Received or plan to receive a licensed live vaccine within 30 days prior to 1st vaccination and to 30 days after the last vaccination. 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. 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. 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) Current or history of alcohol or drug abuse within one year prior to enrollment. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within one year prior to enrollment. Are pregnant, breastfeeding, or plan to become pregnant or breastfeed at any given time during the study. 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. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1A<br>Each subject will receive a 1 mL intramuscular (IM) injection containing 1 microgram of Campylobacter jejuni Conjugate Vaccine 2 (CJCV2) on Days 1, 29, and 57. 3 sentinel subject will be dosed first; if no safety signals are noted within 7 days after sentinel dosing, the remaining 7 subjects will be dosed. N=10 | Biological: CJCV2<br>* 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.<br>|
| Experimental: Group 1B<br>Each subject will receive a 1 mL intramuscular (IM) injection containing 1 microgram of Campylobacter jejuni Conjugate Vaccine 2 (CJCV2) and a full dose of Army Liposome Formulation containing QS-21 (ALFQ) on Days 1, 29, and 57. 3 sentinel subject will be dosed first; if no safety signals are noted within 7 days after sentinel dosing, the remaining 7 subjects will be dosed. N=10 | Drug: ALFQ<br>* 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.<br>Biological: CJCV2<br>* 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.<br>|
| Experimental: Group 2A<br>Each subject will receive a 1 mL intramuscular (IM) injection containing 3 micrograms of Campylobacter jejuni Conjugate Vaccine 2 (CJCV2) on Days 1, 29, and 57. 3 sentinel subject will be dosed first; if no safety signals are noted within 7 days after sentinel dosing, the remaining 7 subjects will be dosed. N=10 | Biological: CJCV2<br>* 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.<br>|
| Experimental: Group 2B<br>Each subject will receive a 1 mL intramuscular (IM) injection containing 3 micrograms of Campylobacter jejuni Conjugate Vaccine 2 (CJCV2) and a full dose of Army Liposome Formulation containing QS-21 (ALFQ) on Days 1, 29, and 57. 3 sentinel subject will be dosed first; if no safety signals are noted within 7 days after sentinel dosing, the remaining 7 subjects will be dosed. N=10 | Drug: ALFQ<br>* 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.<br>Biological: CJCV2<br>* 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.<br>|
| Experimental: Group 3A<br>Each subject will receive a 1 mL intramuscular (IM) injection containing 10 micrograms of Campylobacter jejuni Conjugate Vaccine 2 (CJCV2) on Days 1, 29, and 57. 3 sentinel subject will be dosed first; if no safety signals are noted within 7 days after sentinel dosing, the remaining 7 subjects will be dosed. N=10 | Biological: CJCV2<br>* 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.<br>|
| Experimental: Group 3B<br>Each subject will receive a 1 mL intramuscular (IM) injection containing 10 micrograms of Campylobacter jejuni Conjugate Vaccine 2 (CJCV2) and a full dose of Army Liposome Formulation containing QS-21 (ALFQ) on Days 1, 29, and 57. 3 sentinel subject will be dosed first; if no safety signals are noted within 7 days after sentinel dosing, the remaining 7 subjects will be dosed. N=10 | Drug: ALFQ<br>* 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.<br>Biological: CJCV2<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Medically-Attended Adverse Events (MAAE) |  | Day 1 through 12 months post last vaccination | 
| Occurrence of New-Onset Chronic Medical Conditions (NOCMC) |  | Day 1 through 12 months post last vaccination | 
| Occurrence of Potentially Immune-Mediated Medical Conditions (PIMMC) |  | Day 1 through 12 months post last vaccination | 
| Occurrence of Serious Adverse Events (SAE) |  | Day 1 through 12 months post last vaccination | 
| Occurrence of solicited local Adverse Events (AE) |  | Day 1 through Day 64 | 
| Occurrence of solicited systemic Adverse Events (AE) |  | Day 1 through Day 64 | 
| Occurrence of vaccine-related unsolicited Adverse Events (AE) |  | Day 1 through Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum C. jejuni capsule-specific serum antibody titer (Immunoglobulin G (IgG)) | Antibody in Lymphocyte Supernatant (ALS) assay will measure by enzyme-linked immunosorbent assay (ELISA) the secretion of C. jejuni capsule specific antibodies in cultures of peripheral blood mononuclear cells (PBMCs). | Day 8 through Day 113 | 
| Peak fold rise from baseline in C. jejuni capsule-specific serum antibody titer (Immunoglobulin G (IgG)) | Antibody in Lymphocyte Supernatant (ALS) assay will measure by enzyme-linked immunosorbent assay (ELISA) the secretion of C. jejuni capsule specific antibodies in cultures of peripheral blood mononuclear cells (PBMCs). | Day 8 through Day 113 | 
| Proportion of subjects with a >/= 4-fold rise from baseline in C. jejuni capsule-specific serum antibodies (Immunoglobulin G (IgG)) | Antibody in Lymphocyte Supernatant (ALS) assay will measure by enzyme-linked immunosorbent assay (ELISA) the secretion of C. jejuni capsule specific antibodies in cultures of peripheral blood mononuclear cells (PBMCs). | Day 8 through Day 113 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALFQ, Campylobacter jejuni, Campylobacter jejuni Conjugate Vaccine, CJCV2, Immunogenicity, QS-21, safety