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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by U.S. Army Medical Research and Materiel Command
Sponsor:
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT02067676
First received: February 18, 2014
Last updated: October 10, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Campylobacter Infection
Biological: Capsule-Conjugate Campylobacter Vaccine (CJCV1)
Drug: Alhydrogel®, aluminum hydroxide adjuvant (alum)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity Evaluation of an Intramuscular Capsule-Conjugate Campylobacter Vaccine (CJCV1)

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Presence of local and/or systemic reactogenicity [ Time Frame: up to 7 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Antibody titers against CJCV1 using enzyme-linked immunosorbent assay (ELISA) [ Time Frame: Study Days 0-56 ] [ Designated as safety issue: No ]
    The antibody titer assigned to each sample will represent the geometric mean of duplicate tests performed on 2 different days. Reciprocal endpoint titers < 5 will be assigned a value of 2.5 for computational purposes. Seroconversion will be defined as a > fourfold increase in endpoint titer between pre- and post-vaccination samples and post-vaccination reciprocal titer > 10.

  • Vaccine-specific IgA antibody-secreting cell (ASC) responses [ Time Frame: Study Days 0-56 ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 48
Study Start Date: March 2014
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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).

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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 problems, for example, chronic medical conditions such as psychiatric conditions, diabetes mellitus, hypertension, or any other condition requiring daily therapy that would place a subject at increased risk of 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.
  • Clinically significant abnormalities on physical examination.
  • Use of immunosuppressive medications, 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).
  • 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.
  • Participation in research involving another investigational product 30 days before the planned date of first vaccination or anytime through the last study safety visit.
  • Positive blood test for HBsAg, anti-hepatitis C virus (HCV) antibody, HIV-1.
  • Clinically significant abnormalities on basic laboratory screening.
  • Presence of significant unexplained laboratory abnormalities that, in the opinion of the PI, may potentially confound the analysis of the study results.
  • Regular use (weekly or more often) of anti-diarrheal, anti-constipation, or antacid therapy.
  • Abnormal bowel habits as defined by fewer than 3 stools per week or more than 3 loose/liquid stools per day.
  • Personal or family history of an inflammatory arthritis.
  • Personal history of irritable bowel syndrome.
  • Positive blood test for Human Leukocyte Antigen (HLA)-B27.
  • History of allergy to any vaccine.
  • History of allergy to alum.
  • 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).
  • Occupation involving handling of Campylobacter bacteria or vaccine products currently or in the past 3 years.
  • History of microbiologically confirmed Campylobacter infection.
  • Received previous experimental Campylobacter vaccine or live Campylobacter challenge.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02067676

Contacts
Contact: Robert Gormley, MD, PhD 301-319-7312 robert.gormley@med.navy.mil

Locations
United States, Maryland
Walter Reed Army Institute of Research Recruiting
Silver Spring, Maryland, United States, 20910
Sub-Investigator: Ramiro L Gutierrez, MD, MPH         
Sub-Investigator: Mark S Riddle, MD, DrPH         
Sub-Investigator: Kristopher M Paolino, MD, MTM&H         
Sub-Investigator: Chad Porter, PhD, MPH         
Sub-Investigator: Patricia Guerry, PhD         
Sub-Investigator: Alexander Maue, PhD         
Principal Investigator: Robert Gormley, MD, PhD         
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Robert Gormley, MD, PhD Enteric Disease Department, Naval Medical Research Center
  More Information

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT02067676     History of Changes
Other Study ID Numbers: S-13-09, NMRC.2013.0021
Study First Received: February 18, 2014
Last Updated: October 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
Campylobacter jejuni

Additional relevant MeSH terms:
Campylobacter Infections
Bacterial Infections
Gram-Negative Bacterial Infections
Aluminum Hydroxide
Adjuvants, Immunologic
Antacids
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014