The purpose of this study is to evaluate the safety and tolerability of a two-dose schedule of the recombinant plague vaccine rF1V in healthy volunteers when given as an intramuscular (IM) injection at four ascending dose-levels.

Condition	Treatment or Intervention	Phase
Pneumonic Plague Preventive therapy	Vaccine: rF1V vaccine	Phase I

Further Study Details: 

Primary Outcomes: To evaluate the safety and tolerability of a two-dose schedule of the recombinant plague vaccine rF1V in healthy volunteers when given as an IM injection at four ascending dose-levels.
Secondary Outcomes: To evaluate immunogenicity of a two-dose schedule of rF1V vaccine when given as an IM injection at four ascending dose-levels; To collect and store serum samples for future immunogenicity assays (e.g. ELISA)
Expected Total Enrollment:  40

The Phase 1 clinical trial is designed as an open-label, single-center, dose-escalation study to evaluate the safety, tolerability, and immunogenicity of a two-dose regimen of rF1V in healthy volunteers at four dose-levels (20 ug, 40 ug, 80 ug and 160 ug rF1V) in four sequential cohorts.

Ages Eligible for Study:  18 Years   -   40 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• The volunteer is male or female and 18 to 40 years of age (inclusive) at the time of the first dose of investigational product
• Good health as determined by screening medical history and physical examination
• The volunteer has the following laboratory parameters within normal range: total WBC, Hemoglobin, platelets, LFT (AST, ALT, ALP, Bilirubin) and/or ≤ 1+ proteinuria. Other laboratory parameters must be within 10 % of the upper or lower limits of the normal range of the University of Kentucky clinical laboratory and not clinically significant as assessed by the Investigator and/or Sponsor Medical Monitor.
• The volunteer has a normal electrocardiogram (ECG). However, if a potential volunteer is reported to have a benign ECG abnormality (e.g., sinus bradycardia) the results may be discussed with the Sponsor Medical Monitor and Covalent Medical Monitor. With the agreement of the Investigator, Covalent Medical Monitor and Sponsor Medical Monitor and documentation of the consultation in the volunteer’s study record the Investigator may include the volunteer in the study.
• The volunteer is willing to have his or her blood samples stored for future plague research studies.
• The volunteer has signed the Informed Consent Form, successfully completed (at least 90 % correct) the Test of Understanding, and has signed the HIPAA authorization form.
• The volunteer agrees not to donate blood for at least 30 days following vaccination.
• The volunteer is willing to comply with the requirements of the protocol through the post-vaccination Day 180 (± 7 days) visit.
• Female volunteers must be of non-childbearing potential (i.e., surgically sterilized or postmenopausal), or must not be pregnant (as indicated by a negative serum pregnancy test within 24 hours prior to rF1V administration) or nursing, and must use two types of an acceptable form of FDA-approved contraception (barrier method, Depo-Provera, Norplant, Ortho Evra (birth control patch), oral contraceptives) through 30 days after the second (final) vaccination of rF1V (i.e. Day 58). If abstinent, two forms of birth control are not required

Exclusion Criteria:

• Have a history of plague disease or have received any plague vaccine.
• Have active tuberculosis or other systemic infectious process by review of systems and physical examination.
• Have a history of allergy to kanamycin or aminoglycosides.
• Positive for human immunodeficiency virus (HIV); hepatitis C virus (HCV) or hepatitis B surface antigen (HbsAg)
• Have a history of immunodeficiency, chronic illness requiring continuous or frequent medical intervention, acute/chronic untreated conditions, autoimmune disease, or use of immunosuppressive medications.
• The volunteer has chronic, severe or recurrent joint pain or arthritis of any etiology.
• The volunteer has a positive result on a urine drug screen that tests for common substances of abuse such as amphetamines, barbiturates, benzodiazepines, cocaine, opiates, and cannabinoids. (If positive on screen, confirmatory testing shall be performed where applicable).
• The volunteer has previous diagnosis of any serious psychiatric disorder. For this purpose, serious psychiatric disorder is defined as illness requiring hospitalization within the previous 12 months; routine administration of more than one medication to control anxiety, mood or sleep disorder; or history of suicide attempt.
• The volunteer has received any blood products or immune globulin in the previous six months.
• The volunteer has donated blood within the past 56 days.
• The volunteer received any investigational drug therapy within 30 days before the first dose of rF1V or intends to receive any other investigational drug therapy before the post-vaccination Day 180 (± 7 days) visit.
• The volunteer has a clinically significant abnormality on the ECG.
• The volunteer has a body mass index 40 kg/m2 or is greater than or equal to 100 lbs over the ideal body weight.
• The volunteer has an acute illness, evidence of significant active infection, or evidence of systemic disease at time of enrollment that in the opinion of the Investigator would place the volunteer at an unacceptable risk for injury.
• Have temperature greater than or equal to 100º F on the day of scheduled 1st vaccination.
• Have personal history of multiple sclerosis, since immune system stimulation may exacerbate this disorder.
• Have occupational or other responsibilities that would prevent completion of participation in the study.
• Licensed vaccines are not exclusionary but should be given at least 2 weeks before or after immunization (if live vaccine: 60 days before or after immunization) to avoid potential confusion of adverse reactions.
• Screening laboratory values for total WBC, Hemoglobin, platelets, LFT (AST, ALT, ALP, Bilirubin) are not within normal range and/or more than 1+ proteinuria.
• Have a history of anaphylaxis or other serious adverse reactions to vaccines.
• The female volunteer is pregnant (must have a negative serum pregnancy test within 24 hours prior to each dose of rF1V), lactating or unwilling to use two types of an acceptable form of FDA-approved contraception through 30 days after the second (final) dose of rF1V (i.e. Day 58)
• Are receiving ongoing chemotherapy with immunosuppressive agents such as systemic corticosteroids within 3 months prior to or during the study.
• A total steroid dose of 2mg/kg or 20mg/day within 3 months (ACIP recommendation) and “Burst” therapy within 2 weeks prior to vaccination is permitted. Inhaled and topical steroids are permitted.
• Veterans with prior record of receiving any plague vaccine

Richard N Greenberg, MD      859-323-6327 

Kentucky
      University of Kentucky, Lexington,  Kentucky,  40536,  United States; Recruiting

Study chairs or principal investigators

Richard N Greenberg, MD,  Principal Investigator,  University of Kentucky   

Study ID Numbers:  rF1V-01
Record last reviewed:  November 2004
Last Updated:  November 23, 2004
Record first received:  November 23, 2004
ClinicalTrials.gov Identifier:  NCT00097396
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08