Safety Study of a Capsule-Conjugate Vaccine to Prevent Campylobacter-Caused Diarrhea (CJCV1-01)

Safety and Immunogenicity Evaluation of an Intramuscular Capsule-Conjugate Campylobacter Vaccine (CJCV1)

The purpose of this study is to assess the safety of increasing doses of a potential vaccine against Campylobacter with and without Alhydrogel®, an aluminum hydroxide adjuvant. This study will also assess immune responses induced by the vaccine.

Study Overview

• Status: Completed
• Conditions: Campylobacter Infection
• Intervention / Treatment: Biological: Capsule-Conjugate Campylobacter Vaccine (CJCV1); Drug: Alhydrogel®, aluminum hydroxide adjuvant (alum)

Detailed Description

This is an open-label, dose-escalating study in which a total of 48 healthy volunteers will receive 2 vaccinations (one on Day 0 and one on Day 28 ± 2 days).

There are 3 cohorts (dose levels) with 2 groups of 8 volunteers in each cohort. A cohort will be administered one of 3 intramuscular (IM) doses at 2 μg, 5 μg, or 10 μg of Capsule-Conjugate Campylobacter Vaccine (CJCV1) with or without Alhydrogel®, aluminum hydroxide adjuvant (alum) at 125 μg.

An interval no less than 1 week will separate the last dose of a volunteer group from the first dose of the next volunteer group (receiving different CJCV1 doses). Blood specimens will be collected at intervals to examine systemic and mucosal antigen-specific immune responses. Vaccine safety will be actively monitored during vaccination and for 28 days (± 2 days) following the second vaccination and complete the study with a telephone follow-up approximately 6 months (± 1 month) after the first vaccination. The total duration of participation in this study is up to 270 days (including screening).

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Walter Reed Army Institute of Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adult, male or female, age 18 to 50 years (inclusive) at the time of enrollment.
• Completion and review of comprehension test (achieved 70% accuracy).
• Signed informed consent document.
• Available for the required follow-up period and scheduled clinic visits and telephone follow-up.
• Women: Negative pregnancy test with understanding (through informed consent) to not become pregnant during the study or within three months after the last vaccine dose (Day 28). Sexually active females, unless surgically sterile or at least one year postmenopausal, must have used an effective method of avoiding pregnancy (including oral or implanted contraceptives, intrauterine device (IUD), female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner, or sterile sexual partner) prior to dosing of study vaccine. Female subjects unable to bear children must have a note from a primary care provider or obstetrics and gynaecology (OB/GYN) as proof of documentation (eg, tubal ligation or hysterectomy). If a volunteer becomes pregnant during the study, the PI will notify the study monitor, the sponsor, and the local institutional review board (IRB). The volunteer will be asked to provide serial follow-ups, including copies of clinic visits on the status of her pregnancy as well as health information on her infant following delivery.

Exclusion Criteria:

Health

1. Health problems affecting study participation from medical history (specifically to include chronic medical conditions such as diabetes mellitus and hypertension or any other condition requiring daily therapy that would place the volunteer at increased risk of adverse events (AEs). Study clinicians, in consultation with the PI, will use clinical judgment on a case-by-case basis to assess safety risks under this criterion. The PI will consult with the research monitor as appropriate.
2. Clinically significant abnormalities on physical examination
3. Use of immunosuppressive drugs, such as corticosteroids and chemotherapy, during the course of the study or immunosuppressive illness, including IgA deficiency (defined by serum IgA below level of detection)
4. Women who are pregnant or planning to become pregnant during the study period plus 3 months beyond the last vaccine dose and currently nursing women
5. Participation in research involving another investigational product 30 days before the planned date of first vaccination until the last study safety visit.
6. Positive blood test for HIV-1 (the human immunodeficiency virus and cause of AIDS)
7. Positive blood test for hepatitis B surface antigen (HBsAG; the virus causing hepatitis B)
8. Positive blood test for anti-HCV antibody (the virus causing hepatitis C)
9. Clinically significant abnormalities on basic laboratory screening
10. Presence of significant unexplained laboratory abnormalities that in the opinion of the PI may potentially confound the analysis of the study results Research Specific
11. Regular use (weekly or more often) of anti-diarrheal, anti-constipation, or antacid therapy
12. Abnormal bowel habits as defined by fewer than 3 stools per week or more than 3 loose/liquid stools per day
13. Personal or family history of inflammatory arthritis
14. Personal history of irritable bowel syndrome
15. Positive blood test for HLA-B27
16. History of allergy to any vaccine
17. History of allergy to alum
18. History of Guillain-Barré Syndrome or other neuroimmunological disorders Prior Exposure to Campylobacter
19. History of travelers' diarrhea or residence (> 2 months) in the past 3 years in a country with potentially higher Campylobacter rates to include Africa, South America, Central America, and Asia (except Japan).
20. Occupation involving handling of Campylobacter bacteria or vaccine products currently or in the past 3 years.
21. History of microbiologically confirmed Campylobacter infection.
22. Received previous experimental Campylobacter vaccine or live Campylobacter challenge.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CJCV1 2 μg / Alum 0 μg (1A); Two vaccinations (one on Day 0 and one on Day 28) with an intramuscular dose of Capsule-Conjugate Campylobacter Vaccine (CJCV1) equivalent to 2 μg of polysaccharide and 0 μg of Alhydrogel®, aluminum hydroxide adjuvant (Alum)	Biological: Capsule-Conjugate Campylobacter Vaccine (CJCV1); The capsule of Campylobacter jejuni strain 81-176 (CPS81-176) conjugated to the mutated diphtheria toxin cross-reacting material 197 (CRM197) (lyophilized CPS-CRM197 conjugate) (CJCV1)
Experimental: CJCV1 2 μg / Alum 125 μg (1B); Two vaccinations (one on Day 0 and one on Day 28) with an intramuscular dose of Capsule-Conjugate Campylobacter Vaccine (CJCV1) equivalent to 2 μg of polysaccharide and 125 μg of Alhydrogel®, aluminum hydroxide adjuvant (Alum)	Biological: Capsule-Conjugate Campylobacter Vaccine (CJCV1); The capsule of Campylobacter jejuni strain 81-176 (CPS81-176) conjugated to the mutated diphtheria toxin cross-reacting material 197 (CRM197) (lyophilized CPS-CRM197 conjugate) (CJCV1); Drug: Alhydrogel®, aluminum hydroxide adjuvant (alum)
Experimental: CJCV1 5 μg / Alum 0 μg (2A); Two vaccinations (one on Day 0 and one on Day 28) with an intramuscular dose of Capsule-Conjugate Campylobacter Vaccine (CJCV1) equivalent to 5 μg of polysaccharide and 0 μg of Alhydrogel®, aluminum hydroxide adjuvant (Alum)	Biological: Capsule-Conjugate Campylobacter Vaccine (CJCV1); The capsule of Campylobacter jejuni strain 81-176 (CPS81-176) conjugated to the mutated diphtheria toxin cross-reacting material 197 (CRM197) (lyophilized CPS-CRM197 conjugate) (CJCV1)
Experimental: CJCV1 5 μg / Alum 125 μg (2B); Two vaccinations (one on Day 0 and one on Day 28) with an intramuscular dose of Capsule-Conjugate Campylobacter Vaccine (CJCV1) equivalent to 5 μg of polysaccharide and 125 μg of Alhydrogel®, aluminum hydroxide adjuvant (Alum)	Biological: Capsule-Conjugate Campylobacter Vaccine (CJCV1); The capsule of Campylobacter jejuni strain 81-176 (CPS81-176) conjugated to the mutated diphtheria toxin cross-reacting material 197 (CRM197) (lyophilized CPS-CRM197 conjugate) (CJCV1); Drug: Alhydrogel®, aluminum hydroxide adjuvant (alum)
Experimental: CJCV1 10 μg / Alum 0 μg (3A); Two vaccinations (one on Day 0 and one on Day 28) with an intramuscular dose of Capsule-Conjugate Campylobacter Vaccine (CJCV1) equivalent to 10 μg of polysaccharide and 0 μg of Alhydrogel®, aluminum hydroxide adjuvant (Alum)	Biological: Capsule-Conjugate Campylobacter Vaccine (CJCV1); The capsule of Campylobacter jejuni strain 81-176 (CPS81-176) conjugated to the mutated diphtheria toxin cross-reacting material 197 (CRM197) (lyophilized CPS-CRM197 conjugate) (CJCV1)
Experimental: CJCV1 10 μg / Alum 125 μg (1A); Two vaccinations (one on Day 0 and one on Day 28) with an intramuscular dose of Capsule-Conjugate Campylobacter Vaccine (CJCV1) equivalent to 10 μg of polysaccharide and 125 μg of Alhydrogel®, aluminum hydroxide adjuvant (Alum)	Biological: Capsule-Conjugate Campylobacter Vaccine (CJCV1); The capsule of Campylobacter jejuni strain 81-176 (CPS81-176) conjugated to the mutated diphtheria toxin cross-reacting material 197 (CRM197) (lyophilized CPS-CRM197 conjugate) (CJCV1); Drug: Alhydrogel®, aluminum hydroxide adjuvant (alum)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Presence of Related/Not Related Local and/or Systemic Reactogenicity (Adverse Events)	Vaccine safety will be assessed by evaluating post-vaccination local and systemic reactions through targeted physical exams, symptom surveys, and other adverse event (AE) monitoring. All subjects will be observed in the clinic for at least 30 minutes after receipt of the investigational product. Approximately 48 hours after vaccination, subjects will return to the Clinical Trials Center for observation and reporting of any local and/or systemic AEs. Seven days after vaccine administration, subjects will return to the Clinical Trials Center to review their memory aids with study personnel and to report any AEs. In addition to planned visits, if a subject experiences any unanticipated AE, the subject will be seen by one of the study investigators. All AEs will be coded for onset date, duration, severity, and potential relationship to the investigational product.	up to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency (%) of Vaccine-specific Immune Responses by Assay and Antigen Using Enzyme-linked Immunosorbent Assay (ELISA)	Primary immunologic parameters, serum samples were assessed for the antibody titers against Campylobacter jejuni conjugate vaccine1 (CJCV1) using ELISA (enzyme-linked immunosorbent assay) based methods. Antibody-secreting cell(s) (ASCs): >0.5 per 10(6) Peripheral blood mononuclear cell (PBMCs) in the baseline sample. When the number of baseline ASCs is less than 0.5 per 10(6) PBMCs, a subject was considered a responder if the post-vaccination value was greater than 1.0 per 10(6) PBMCs. ((6) is superscript).; = Seroconversion was defined as >4fold increase in endpoint titer between pre- and post-vaccine samples and a post-vaccine reciprocal titer >10.; = Response is defined as a >2fold increase over the baseline value of ASC per 10(6) PBMCs, when the number of ASCs is >0.5 per 10(6) PBMCs in the baseline sample. When the number of baseline ASCs is less than 0.5 per 10(6) PBMCs, a subject was considered a responder if the post-vaccine value was greater than 1.0 per 10(6) PBMCs.	Study Days 0-56
Vaccine-specific Geometric Mean Titers (GMT) of Anti-CPS IgG Antibody-secreting Cells	Anti-CPS IgG ASC Responses - GMTs with 95% CI. A positive immunoglobulin A (IgA)-ASC response will be defined as a > twofold increase over the baseline value of the ASCs per 10^6 peripheral blood mononuclear cells (PBMCs). A subject will be considered a responder if the post-vaccination value is greater than 2.0 per 10^6 PBMCs. Blood samples will also be utilized to explore in vitro production of interferon (IFN)-(gamma).	Study Days 0-56
Vaccine-specific Anti-CRM^197 IgA Antibody-secreting Cell (ASC) Responses	Anti-CRM^197 IgG ASC Responses - GMTs with 95% CI. A positive immunoglobulin A (IgA)-ASC response will be defined as a > twofold increase over the baseline value of the ASCs per 10^6 peripheral blood mononuclear cells (PBMCs). A subject will be considered a responder if the post-vaccination value is greater than 2.0 per 10^6 PBMCs. Blood samples will also be utilized to explore in vitro production of interferon (IFN)-(gamma).	Study Days 0-56
Interferon Titers Among All Cohorts	CRM197-specific interferon-y (IFNy) responses measured from PBMC on day0, 28 and 56	Day 0, 28 and 56

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: Walter Reed Army Institute of Research (WRAIR)
• Investigators: Principal Investigator: Ramiro Gutierrez, MD, Enteric Disease Department, Naval Medical Research Center

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2014
• Primary Completion (Actual): September 24, 2014
• Study Completion (Actual): January 22, 2016

Study Registration Dates

• First Submitted: February 18, 2014
• First Submitted That Met QC Criteria: February 19, 2014
• First Posted (Estimate): February 20, 2014

Study Record Updates

• Last Update Posted (Actual): February 23, 2018
• Last Update Submitted That Met QC Criteria: January 29, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Campylobacter jejuni
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Campylobacter Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Gastrointestinal Agents; Adjuvants, Immunologic; Antacids; Aluminum Hydroxide
• Other Study ID Numbers: S-13-09; NMRC.2013.0021 (Other Identifier: Naval Medical Research Center IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: WRAIR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No