Safety Study of a Capsule-Conjugate Vaccine to Prevent Campylobacter-Caused Diarrhea

NCT ID: NCT02067676

Last Updated: 2018-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-21
• Study Completion Date: 2016-01-22

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).

Conditions

Campylobacter Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Capsule-Conjugate Campylobacter Vaccine (CJCV1)

Intervention Type: BIOLOGICAL

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)

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)

Group Type: EXPERIMENTAL

Capsule-Conjugate Campylobacter Vaccine (CJCV1)

Intervention Type: BIOLOGICAL

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)

Alhydrogel®, aluminum hydroxide adjuvant (alum)

Intervention Type: DRUG

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)

Group Type: EXPERIMENTAL

Capsule-Conjugate Campylobacter Vaccine (CJCV1)

Intervention Type: BIOLOGICAL

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)

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)

Group Type: EXPERIMENTAL

Capsule-Conjugate Campylobacter Vaccine (CJCV1)

Intervention Type: BIOLOGICAL

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)

Alhydrogel®, aluminum hydroxide adjuvant (alum)

Intervention Type: DRUG

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)

Group Type: EXPERIMENTAL

Capsule-Conjugate Campylobacter Vaccine (CJCV1)

Intervention Type: BIOLOGICAL

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)

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)

Group Type: EXPERIMENTAL

Capsule-Conjugate Campylobacter Vaccine (CJCV1)

Intervention Type: BIOLOGICAL

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)

Alhydrogel®, aluminum hydroxide adjuvant (alum)

Intervention Type: DRUG

Interventions

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)

Intervention Type: BIOLOGICAL

Alhydrogel®, aluminum hydroxide adjuvant (alum)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Walter Reed Army Institute of Research (WRAIR)

FED

Sponsor Role: collaborator

U.S. Army Medical Research and Development Command

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ramiro Gutierrez, MD

Role: PRINCIPAL_INVESTIGATOR

Enteric Disease Department, Naval Medical Research Center

Locations

Walter Reed Army Institute of Research

Silver Spring, Maryland, United States

Countries

United States

Other Identifiers

NMRC.2013.0021

Identifier Type: OTHER

Identifier Source: secondary_id

S-13-09

Identifier Type: -

Identifier Source: org_study_id