Dose Escalation Trial of a Plague Vaccine, Flagellin/F1/V, in Healthy Adult Volunteers

• Register: ClinicalTrials.gov
• Last refreshed on: 20 May 2013
• Main ID: NCT01381744
• Date of registration: 23/06/2011
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Dose Escalation Trial of a Plague Vaccine, Flagellin/F1/V, in Healthy Adult Volunteers
• Scientific title: A Phase I Safety and Immunogenicity Dose Escalation Trial of Plague Vaccine, Flagellin/F1/V, In Healthy Adult Volunteers
• Date of first enrolment: February 2012
• Target sample size: 48
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01381744
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Countries of recruitment

United States

Contacts

• Name: Sharon E Frey

Key inclusion & exclusion criteria

Inclusion Criteria:

Inclusion criteria that must met prior to the initial vaccination:

- 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 (6 months after last
immunization).

- 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.

Inclusion criteria that must be met prior to the second vaccination:

- Never had plague or disease caused by Yersinia pestis.

- Satisfactory medical assessment with no clinically significant and relevant
abnormalities as established by medical history.

- If the subject is female and of childbearing potential, negative urine or serum
pregnancy test within 24 hours prior to vaccination.

- If the subject is female and of childbearing potential, she has remained on the same
contraception method as used 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., IUDs, 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.

- Post dose one safety labs (Day 14) have to be within institutional normal limits, or
as otherwise specified at the Day 14 post the initial vaccination or any observed
laboratory toxicities have to be resolved prior to the second vaccination.

Exclusion Criteria:

Exclusion criteria prior to 1st vaccination:

- 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.

- 10% 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.

- Use of any other experimental agent (i.e. chemical or biological entity not
registered for clinical use) within 30 days prior to vaccination and for the duration
of the study

- Donation of a unit of blood within 56 days prior to vaccination.

- Acute febrile illness (>100.2 degrees F) on the day of vaccination.

- Any condition that, in the opinion of the investigator, might interfere with study
objectives or would make administration of the study vaccine hazardous or make it
difficult to monitor adverse effects.

- Study personnel.

- Current abuse of alcohol or drug addiction that in the opinion of the Investigator
may interfere with the subject's ability to comply with trial procedures.

Exclusion criteria that apply prior to second vaccination:

- Subject that were discontinued due to meeting individual halting rule after the first
vaccination.

- History of immunodeficiency or suspected impairment of immunologic functioning.

- Known or suspected history of plague vaccination, ex


Age minimum: 18 Years
Age maximum: 45 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Plague

Intervention(s)

Biological: Flagellin/F1/V

Drug: Placebo

Primary Outcome(s)

Incidence of Grade 3 or above laboratory toxicities associated with vaccination for each dose group. [Time Frame: Through Day 42 (14 days after the second vaccination).]

Incidence of serious adverse events (SAEs)associated with vaccination for each dose group. [Time Frame: 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. [Time Frame: Days: 0, 14, 28, 42, 56, 68 and 208.]

Secondary Outcome(s)

Assessment of cytokine responses (TNF-alpha, IL-6 and IL-1 beta) as measured in serum samples. [Time Frame: 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).]

Distribution of the cytokine expression levels in peripheral blood mononuclear cells (PBMCs) following ex vivo stimulation for each dose group. [Time Frame: Day 0, 14, 42, 56, and 68.]

Occurrence of localized reactogenicity symptoms for each dose group. [Time Frame: Within 15 days (Day 0-14) of each vaccination.]

Occurrence of systemic reactogenicity symptoms for each dose group. [Time Frame: Within 15 days (Day 0-14) of each vaccination.]

Occurrence of unsolicited adverse events (AEs) for each dose group. [Time Frame: Within 28 days of each vaccination.]

Secondary ID(s)

08-0066

N01AI80003C

Source(s) of Monetary Support

Please refer to primary and secondary sponsors