Phase II Tularemia Vaccine Comparison

NCT01150695 | Completed Phase 2

• 1 other identifier: 08-0006
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 5

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.

Conditions

Tularaemia

Keywords

vaccine, Francisella tularensis, Tularemia, rabbit fever, parent protocol

Outcome Measures

Primary Outcomes (4)

• Safety: incidence of vaccine-associated serious adverse events (SAEs).

  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.

  Visits 7 or 8 post vaccination (Day 28 or Day 56).

• Safety: incidence of Grade 3 or 4 laboratory values.

  Through Day 28 of the study.

• 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.

  By study Visit 5 (7-9 days post vaccination).

Secondary Outcomes (6)

• 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 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).

• Safety: occurrence of solicited local adverse events (AE)s.

  Within 28 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)..

Study Arms (2)

Group A (DVC-LVS)

EXPERIMENTAL

Single dose of the Dynport Vaccine Company Live Vaccine Strain (DVC-LVS) product in one arm and normal saline (NS) control in the other arm on Day 0.

Other: Placebo; Biological: Undiluted Francisella tularensis live attenuated vaccine

Group B (USAMRIID-LVS)

EXPERIMENTAL

Single dose of the United States Army Medical Research Institute of Infectious Diseases Live Vaccine Strain (USAMRIID-LVS) product in one arm and normal saline (NS) control in the other arm on Day 0.

Other: Placebo; Biological: Undiluted Francisella tularensis live attenuated vaccine

Interventions

Placebo OTHER

Normal saline will be administered to all subjects as a control and will be given at the same visit as the vaccine (Day 0).

Group A (DVC-LVS); Group B (USAMRIID-LVS)

Undiluted Francisella tularensis live attenuated vaccine BIOLOGICAL

Undiluted Francisella tularensis live attenuated vaccine \[approximately 1x10\^9 colony forming units (cfu)/mL\] produced by Dynport Vaccine Company. Administered by scarification in the ulnar aspect of the volar surface (palm side) of the forearm midway between the wrist and the elbow.

Group A (DVC-LVS)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Completion of Volunteer Questionnaire
• Willingness to comply with protocol requirements
• Provides informed consent before any protocol procedures are performed
• Availability for follow up for 6 months after vaccination

You may not qualify if:

• 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.
• 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.
• Receipt of licensed live attenuated vaccine within 30 days prior to vaccination or planned receipt of licensed live attenuated vaccine within 28 days post vaccination.
• Use of any other experimental agent within 30 days prior to vaccination and for the duration of the study.
• Previous vaccination against tularemia.
• Previous treatment for tularemia or history of exposure to tularin.
• Known hypersensitivity to gelatin or other components contained in the vaccine (e.g. glucose cysteine hemin agar).
• History of sensitivity to streptomycin or tetracyclines (including doxycycline).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (5)

Emory Vaccine Center - The Hope Clinic

Decatur, Georgia, 30030-1705, United States

Location

University of Iowa - Vaccine Research & Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

University of Maryland School of Medicine - Center for Vaccine Development - Baltimore

Baltimore, Maryland, 21201-1509, United States

Location

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, 77030-3411, United States

Location

Related Publications (2)

• Goll JB, Bosinger SE, Jensen TL, Walum H, Grimes T, Tharp GK, Natrajan MS, Blazevic A, Head RD, Gelber CE, Steenbergen KJ, Patel NB, Sanz P, Rouphael NG, Anderson EJ, Mulligan MJ, Hoft DF. The Vacc-SeqQC project: Benchmarking RNA-Seq for clinical vaccine studies. Front Immunol. 2023 Jan 19;13:1093242. doi: 10.3389/fimmu.2022.1093242. eCollection 2022.

  PMID: 36741404 DERIVED

• Mulligan MJ, Stapleton JT, Keitel WA, Frey SE, Chen WH, Rouphael N, Edupuganti S, Beck A, Winokur PL, El Sahly HM, Patel SM, Atmar RL, Graham I, Anderson E, El-Kamary SS, Pasetti MF, Sztein MB, Hill H, Goll JB; DMID 08-0006 Tularemia Vaccine Study Group. Tularemia vaccine: Safety, reactogenicity, "Take" skin reactions, and antibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain - A phase 2 randomized clinical Trial. Vaccine. 2017 Aug 24;35(36):4730-4737. doi: 10.1016/j.vaccine.2017.07.024. Epub 2017 Jul 24.

  PMID: 28750854 DERIVED

MeSH Terms

Conditions

Tularemia

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Tick-Borne Diseases; Vector Borne Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• 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 24, 2010
• First Posted: June 25, 2010
• Study Start: September 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: January 13, 2016

Record last verified: 2013-03

Locations

US (5)