Clinical trial NCT02067676: Safety Study of a Capsule-Conjugate Vaccine to Prevent Campylobacter-Caused Diarrhea
Official title: Safety and Immunogenicity Evaluation of an Intramuscular Capsule-Conjugate Campylobacter Vaccine (CJCV1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Campylobacter Infection
Keywords: Campylobacter jejuni
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: Walter Reed Army Institute of Research (WRAIR)
First posted: 2014-02-20
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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 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

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.

Primary outcomes:
measure: Safety: Presence of Related/Not Related Local and/or Systemic Reactogenicity (Adverse Events)
timeFrame: up to 7 days
Secondary outcomes:
measure: Frequency (%) of Vaccine-specific Immune Responses by Assay and Antigen Using Enzyme-linked Immunosorbent Assay (ELISA)
timeFrame: Study Days 0-56
measure: Vaccine-specific Geometric Mean Titers (GMT) of Anti-CPS IgG Antibody-secreting Cells
timeFrame: Study Days 0-56
measure: Vaccine-specific Anti-CRM^197 IgA Antibody-secreting Cell (ASC) Responses
timeFrame: Study Days 0-56
measure: Interferon Titers Among All Cohorts
timeFrame: Day 0, 28 and 56
Other outcomes:
Locations:
city: Silver Spring
country: United States
facility: Walter Reed Army Institute of Research
state: Maryland
Study officials:
affiliation: Enteric Disease Department, Naval Medical Research Center
name: Ramiro Gutierrez, MD
role: PRINCIPAL_INVESTIGATOR
References: