A Phase II, Multi-Center, Double-Blind, Randomized Trial Comparing the Safety and Immunogenicity of a Francisella Tularensis Live Vaccine Strain (LVS) Vaccine Produced by DynPort Vaccine Company (DVC-LVS) to a LVS Vaccine in Use by the United States Army Medical Research Institute of Infectious Diseases (USAMRIID-LVS)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Tularaemia
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 228
- Locations
- 5
- Primary Endpoint
- Proportion of subjects that develop a positive "take" response, as assessed by the clinical site, defined as the development of an erythematous papule, vesicle, and/or eschar with or without underlying induration.
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this study is to compare 2 experimental vaccines that could provide protection from the disease, tularemia. This research will compare the ability of the vaccines to cause the body to develop an immune (protective) response and obtain more information on side effects of the vaccines. About 220 male and non-pregnant female volunteers 18 to 45 years will participate. Volunteers will be assigned to 1 of 2 vaccine groups by chance. About half of the volunteers will be placed in the DVC-LVS vaccine group and half of volunteers will be placed in the USAMRIID-LVS vaccine group. Additionally, both groups will receive an injection of placebo (inactive salt water). Study procedures include physical exam and blood and urine samples. Evaluation of the vaccination sites will be performed as well as blood samples to measure the body's response to the vaccine. Participants will be involved in the study for about 6 months.
Detailed Description
Francisella (F.) tularensis is the organism responsible for tularemia. The organism can infect many different vertebrate and invertebrate hosts, but mostly rodents and lagomorphs. Transmission to humans is generally via an insect vector, such as ticks, mosquitoes, and biting flies, or from handling contaminated animal products or carcasses. F. tularensis is a highly infectious bacterium, with human infection and disease occurring with as few as 10 organisms, and mortality rates approaching 30 percent if untreated. Clinical presentation of tularemia varies in severity depending on the virulence of the organism, the route of entry, the extent of system involvement, and the immune status of the host. Following an incubation period of 3 to 5 days, individuals have an abrupt onset of fever, chills, headache, malaise, anorexia, and fatigue. The clinical presentation of the disease can include one or more the following forms: ulceroglandular (the most common form of the disease), glandular, oculoglandular, pharyngeal, gastrointestinal, pneumonic or typhoidal. This study is a Phase II, multi-center, double-blind, randomized, trial comparing the safety and immunogenicity of a Francisella tularensis live vaccine strain (LVS) vaccine produced by DynPort Vaccine Company (DVC-LVS) to a LVS vaccine in use by the United States Army Medical Research Institute of Infectious Diseases (USAMRIID-LVS). Study Group A will include 110 volunteers who will be vaccinated with a single dose of the DVC LVS product in one arm and normal saline (NS) control in the other arm on Day 0. Group B will include 110 volunteers who will be vaccinated with a single dose of the USAMRIID-LVS product in one arm and normal saline (NS) control in the other arm on Day 0. Both vaccines will be administered by scarification. Approximately 100 microliters aliquot will be withdrawn and placed on the skin, a bifurcated needle will then be used to puncture the skin 15 times through the droplet. The primary objectives are: (Safety): assess the frequency of serious adverse events (SAEs) and Grade 3 and 4 laboratory values following vaccination with either DVC-LVS or USAMRIID-LVS vaccine; (Take): assess the frequency of "take" (defined as the development of an erythematous papule, vesicle, and/or eschar with or without underlying induration) following vaccination with either the DVC-LVS or USAMRIID-LVS vaccine; and (Immunogenicity): assess the rate of seroconversion following vaccination with either the DVC-LVS or the USAMRIID-LVS vaccine as measured by a tularemia-specific microagglutination assay. The secondary objectives are: (Safety): assess the incidence of adverse events (AEs) following vaccination with either the DVC-LVS or the USAMRIID-LVS vaccine; (Take): assess "take" frequency and difference between vaccine groups as assessed by an independent committee following vaccination with either the DVC-LVS or USAMRIID- LVS vaccine; and (Immunogenicity): assess antibody responses for each group following vaccination with DVC-LVS or USAMRIID-LVS vaccine as measured by a tularemia-specific microagglutination assay. Parent protocol to sub-study 10-0019.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males and non-pregnant females between the ages of 18 and 45 years, at the day of vaccination
- •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 vaccination.
- •If the subject is female and of childbearing potential, she agrees to practice abstinence from sexual intercourse with men (vaginal penetration by a penis, coitus) or use acceptable contraception, for 56 days following vaccination in order to avoid pregnancy:
- •A woman is considered of childbearing potential unless post-menopausal (greater than or equal to 1 year without menses) or surgically sterilized (tubal ligation, bilateral oophorectomy, or hysterectomy)
- •Acceptable contraception methods are restricted to effective devices \[intrauterine devices (IUDs), NuvaRing®\] or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, condoms with spermicidal agents, monogamous relationship with a vasectomized partner or successful Essure placement with documented confirmation test at least 3 months after the procedure.
- •All clinical laboratory values must be within normal limits for age and gender with the following exceptions:
- •White Blood Cell Count: 3.0-10.8 thou/mcl.
- •Absolute Neutrophil count: \>/= 1.5 thou/mcl
- •ALT, AST and LDH \</= 1.25 x ULN
- •Glucose: \</= 115 mg/dl
Exclusion Criteria
- •Current use of antibiotics or antibiotic treatment within last 7 days.
- •Current treatment with chemotherapy.
- •Use of immunosuppressive or immunomodulatory agents including parenteral, inhaled, or oral corticosteroids within the last 4-weeks. Use of corticosteroid nasal sprays is permissible. Persons who have used topical steroid can be enrolled after their therapy is completed.
- •History of splenectomy.
- •Has been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others, within the past 10 years. ((Subjects with a psychiatric disorder (not meeting exclusion criteria, e.g. attention-deficit hyperactivity disorder) that is controlled for a minimum of 3 months and the investigator has determined that the subject's mental status will not compromise the subject's ability to comply with protocol requirements may be enrolled)).
- •The subject is taking any of the following psychiatric drugs:
- •aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine, thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, trifluopromazine, chlorprothixene, chlorpromazine, perphenazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate or lithium citrate.
- •The subject is taking more than one antidepressant drug not included in the list above ((Subjects taking only one antidepressant drug (not listed in excluded psychiatric drugs) who are stable for at least 3 months prior to enrollment without decompensating are allowed enrollment into the study provided the investigator determines the subjects' mental status will not compromise the subjects' ability to comply with protocol requirements.
- •History of receiving blood or blood products (such as blood transfusion, platelet transfusion, immunoglobulins, hyperimmune serum) in the previous three months.
- •Receipt of licensed inactivated vaccine 14 days prior to vaccination or planned receipt of licensed inactivated vaccine within 14 days post vaccination.
Outcomes
Primary Outcomes
Proportion of subjects that develop a positive "take" response, as assessed by the clinical site, defined as the development of an erythematous papule, vesicle, and/or eschar with or without underlying induration.
Time Frame: By study Visit 5 (7-9 days post vaccination).
Safety: incidence of vaccine-associated serious adverse events (SAEs).
Time Frame: Throughout the course of the study.
Immunogenicity: proportion of subjects that seroconvert (greater than or equal to 4-fold rise in antibody titer) as measured by a tularemia-specific microagglutination assay.
Time Frame: Visits 7 or 8 post vaccination (Day 28 or Day 56).
Safety: incidence of Grade 3 or 4 laboratory values.
Time Frame: Through Day 28 of the study.
Secondary Outcomes
- Safety: occurrence of solicited systemic AEs.(Within 28 days post vaccination.)
- Take: difference in the proportion of subjects that develop a positive "take" response between the two vaccine groups as assessed by an independent blinded "take committee".(Study Visit 5 (7-9 days post vaccination).)
- Immunogenicity: geometric mean titers (GMT) of peak microagglutination titer for each arm of the study. For each subject, the peak titer is defined by the maximum titer among all the available measures.(Visits 6, 7 and 8 post vaccination (Day 14, Day 28 and Day 56)..)
- Take: proportion of subjects that develop a positive "take" response, as assessed by an independent blinded "take committee," following review of photographs taken of the vaccination and placebo sites.(Study Visit 5 (7-9 days post vaccination).)
- Safety: occurrence of solicited local adverse events (AE)s.(Within 28 days post vaccination.)
- Take: difference in the proportion of subjects that develop a positive "take" response between the two vaccine groups as assessed by the clinical site.(Study Visit 5 (7-9 days post vaccination).)