Dose Escalation Trial of a Plague Vaccine, Flagellin/F1/V, in Healthy Adult Volunteers
A Phase I Safety and Immunogenicity Dose Escalation Trial of Plague Vaccine, Flagellin/F1/V, In Healthy Adult Volunteers
2 other identifiers
interventional
48
1 country
1
Brief Summary
Plague is an infectious disease of animals and humans caused by bacteria, Yersinia pestis. Modern antibiotics are effective against plague, but if an infected person is not treated promptly the disease is likely to cause illness or death. The purpose of this study is to evaluate at the safety, immunogenicity (bodily defense reaction), and tolerability of a new research vaccine. Up to 48 people will be enrolled in this study at the Center for Vaccine Development at Saint Louis University. Four groups of 12 volunteers will be given vaccine or placebo (inactive substance) one group at a time starting with the lowest dose working up to the highest dose. Shots will be given in the arm 2 times separated by 28 days. Study procedures include: physical exam, blood samples, and recording temperature and side effects in a memory aid. Participants will be involved in study related procedures for about 13 months.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2012
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 23, 2011
CompletedFirst Posted
Study publicly available on registry
June 27, 2011
CompletedStudy Start
First participant enrolled
February 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2014
CompletedJanuary 29, 2016
October 1, 2014
2.5 years
June 23, 2011
January 28, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Incidence of Grade 3 or above laboratory toxicities associated with vaccination for each dose group.
Through Day 42 (14 days after the second vaccination).
Incidence of serious adverse events (SAEs)associated with vaccination for each dose group.
Throughout the duration of the study (Visit 11, 365 + 14 days after the second vaccination or through termination visit, if terminated early).
Peak antibody titer [immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) for F1 and V antigen] for each dose group as determined by analysis of serum samples.
Days: 0, 14, 28, 42, 56, 68 and 208.
Secondary Outcomes (5)
Distribution of the cytokine expression levels in peripheral blood mononuclear cells (PBMCs) following ex vivo stimulation for each dose group.
Day 0, 14, 42, 56, and 68.
Occurrence of unsolicited adverse events (AEs) for each dose group.
Within 28 days of each vaccination.
Occurrence of systemic reactogenicity symptoms for each dose group.
Within 15 days (Day 0-14) of each vaccination.
Occurrence of localized reactogenicity symptoms for each dose group.
Within 15 days (Day 0-14) of each vaccination.
Assessment of cytokine responses (TNF-alpha, IL-6 and IL-1 beta) as measured in serum samples.
Serum samples obtained on the day of vaccination, and on Visit 3 and 6 (1 day after each vaccination) and Visit 4 and 7 (14 days after each vaccination).
Study Arms (4)
Group 3: 6 mcg Flagellin/F1/V
EXPERIMENTAL12 subjects will receive 6 mcg of Flagellin/F1/V or placebo on Day 0 and Day 28.
Group 4: 10 mcg Flagellin/F1V
EXPERIMENTAL12 subjects will receive 10 mcg of Flagellin/F1/V or placebo on Day 0 and Day 28.
Group 2: 3 mcg Flagellin/F1/V
EXPERIMENTAL12 subjects will receive 3 mcg of Flagellin/F1/V or placebo on Day 0 and Day 28.
Group 1: 1 mcg Flagellin/F1/V
EXPERIMENTAL12 subjects will receive 1 microgram (mcg) of Flagellin/F1/V or placebo on Day 0 and Day 28.
Interventions
Flagellin/F1/V recombinant fusion protein vaccine administered by the intramuscular route on Days 0 and 28 at a dose of 1, 3, 6, or 10 micrograms (mcg). It is a clear, colorless solution.
Phosphate buffered saline (PBS) used as diluent and placebo.
Eligibility Criteria
You may qualify if:
- At least 18 and less than or equal to 45 years of age at the time of first vaccination.
- Never had plague or disease caused by Yersinia pestis.
- Able to provide informed consent.
- Read, signed, and dated informed consent document.
- Available for follow-up for the planned duration of the study.
- Satisfactory medical assessment with no clinically significant and relevant abnormalities as established by medical history and physical examination at screening.
- If the subject is female and of childbearing potential, negative serum pregnancy test at screening and negative urine or serum pregnancy test within 24 hours prior to each vaccination.
- If the subject is female and of childbearing potential, she agrees to use acceptable contraception and remain on the same method during the study as they were using prior to entering the study, and not become pregnant for 28 days following the last vaccination. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized. Acceptable contraception methods are restricted to effective devices \[e.g., intrauterine device (IUD), NuvaRing®\] or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, a monogamous relationship with a vasectomized partner and abstinence from sexual intercourse with men.
- Negative enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV).
- Negative hepatitis B surface antigen and negative antibody to hepatitis C virus.
- Safety labs have to be within institutional normal limits, or as otherwise specified.
- Weight: greater than or equal to 110 pounds.
- Body Mass Index (BMI) of greater than or equal to 19 and less than 33.
- Subject agrees not to donate blood for the duration of their study participation.
- Never had plague or disease caused by Yersinia pestis.
- +4 more criteria
You may not qualify if:
- History of immunodeficiency or suspected impairment of immunologic functioning.
- Known or suspected history of plague vaccination.
- Pregnant women or women that are breastfeeding.
- Uncontrolled hypertension (defined as systolic blood pressure \>140 mm Hg and/or diastolic blood pressure \> 90 mm Hg).
- Subject is on statin therapy.
- % or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's risk assessment tool (http://hin.nhlbi.nih.gov/atpiii/calculator.asp). NOTE that this criterion applies only to subjects 20 years of age and older AND only if at least one of the following apply: have smoked a cigarette in the past month, have hypertension (defined as systolic blood pressure \>140 mm Hg) or are on antihypertensive medication and/or have a family history of coronary heart disease in male first-degree relative (father or brother) \<55 years of age or a female first-degree relative (mother or sister) \<65 years of age.
- Current use or use within 30 days of screening of immunosuppressive medication or corticosteroids (use of topical or nasal corticosteroids is allowed). Persons who are using a topical steroid can be enrolled after their therapy is completed. Inhaled steroids for asthma are not permissible.
- Chronic use of non-steroidal anti-inflammatory drug therapy
- Malignancy not including squamous cell skin cancer or basal cell skin cancer unless at the vaccination site or history of skin cancer at the vaccination site.
- Active autoimmune disease \[Persons with vitiligo or thyroid disease (e.g., taking thyroid hormone replacement) are not excluded\].
- Receipt of any vaccine 14 days prior to vaccination.
- Receipt of live attenuated vaccine within 30 days prior to vaccination.
- Planned receipt of any vaccine including allergy shots during the 28 day vaccination period and through 14-days post the second vaccination (Visit 7).
- Receipt of blood products or immunoglobulin within six months prior to vaccination.
- Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol.
- +26 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Saint Louis University - Center for Vaccine Development
St Louis, Missouri, 63104-1015, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 23, 2011
First Posted
June 27, 2011
Study Start
February 1, 2012
Primary Completion
August 1, 2014
Study Completion
August 1, 2014
Last Updated
January 29, 2016
Record last verified: 2014-10