Clinical trial NCT00050518: APSV in Vaccinia Naive Adults
Official title: A Multicenter, Double-Blind, Randomized Study of the Safety and Efficacy of Aventis Pasteur's Smallpox Vaccine, USP (APSV) in Vaccinia-Naive Adults.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Smallpox
Keywords: Smallpox
Aventis Pasteur
Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2002-12-13
Enrollment: 444
Sex: ALL
Minimum age (years): 18
Maximum age (years): 32
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The study seeks to define, with precision, the safety and efficacy of APSV, two dose potencies of one lot in vaccinia-naive adults. The ability of this vaccine to induce a classic �take� as defined by formation of a lesion at the injection site consistent with the �Jennerian� process (see Appendix A) and vaccine specific immune responses will be assessed. The local cutaneous lesion is considered to be a surrogate for clinical effectiveness of live, replicating smallpox vaccines. Neutralizing antibody formation has been correlated with takes for the Dryvax vaccine and is considered to be cross-protective for other orthopoxviruses, including variola. The study also seeks to characterize preliminarily the cell mediated immune (CMI) response to APSV (as compared to Dryvax).

Detailed description: A Multicenter, double blind, randomized trial in which each volunteer will receive one of 2 dose concentrations of one of two lots of Aventis Pasteur Smallpox Vaccine as a single vaccination (undiluted, 1:5 dilution). Volunteers without a take at day 7 - 9 will be offered a vaccination with Dryvax at the end of the study.

Eligibility criteria: INCLUSION CRITERIA:

* Adequate renal function defined as a serum creatinine 1.5 mg/dL; urine protein \< 100mg/ dL or trace or negative proteinuria (by dipstick), and a calculated creatinine clearance \>55 mL/min. Formula for calculations is contained within the Manual of Procedures.

(Note: Renal function is measured to ensure that subjects could meet criteria for use of cidofovir if needed).

* Age 18-32 (children are excluded due to concerns of safety, including autoinoculation).
* Willing to sign informed consent.
* Availability for follow-up for planned duration of the study (56 days following the last vaccination).
* Acceptable medical history by screen evaluation form and brief assessment.
* Absence of a typical vaccinia scar and negative history of smallpox vaccination.
* Negative urine or serum pregnancy test for women of childbearing potential.
* If the volunteer is female and of childbearing potential, she agrees to use acceptable contraception, and not become pregnant for the duration of the study. (Acceptable contraception includes implants, injectables, combined oral contraceptives, effective intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner).
* Negative ELISA for HIV or negative Western blot for subjects who have a positive ELISA and have participated in an HIV vaccine trial.
* Negative hepatitis B surface antigen and negative antibody to hepatitis C virus.
* Negative urine glucose by dipstick.
* ALT \< 1.5 times institutional upper limit of normal.

EXCLUSION CRITERIA:

* Allergies to any component of the vaccines (e.g., polymyxin B sulfate, dihydrostreptomycin sulfate, chlorotetracycline hydrochloride).
* History of immunodeficiency.
* Serology positive for HIV, hepatitis B, or hepatitis C at the screening visit.
* Known or suspected impairment of immunologic function including, but not limited to clinically significant liver disease.
* Diabetes mellitus.
* Moderate to severe kidney impairment.
* Malignancy with the exception of squamous cell or basal cell skin cancer.
* Autoimmune disease.
* Use of immunosuppressive medication.
* Corticosteroid nasal sprays are permissible.
* Medical or psychiatric condition or occupational responsibilities which preclude subject compliance with the protocol.
* History of illegal injection drug use.
* Live attenuated vaccines within 60 days of study.
* Use of experimental agents within 30 days prior to study.
* Any history of vaccination with any vaccinia vectored or other pox vectored experimental vaccine.
* Smallpox vaccination since 1990 (Vaccinia experience cohorts).
* Typical vaccinia scar or history of smallpox vaccination (Vaccinia naive cohorts only).
* Receipt of blood products or immunoglobulin in the past 6 months.
* Recent donation of the equivalent of a pint of blood within the 30 days prior to enrollment.
* Acute febrile illness (100.5 F) on the day of vaccination.
* Pregnant or lactating women.
* Eczema of any degree or history of eczema.
* History of exfoliative skin disorders/conditions.
* Any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2x2 cm.
* Household contacts/sexual contacts with, or close and frequent occupational exposure to, any of the following: pregnant women, children \< 12 months of age, people with eczema or history of eczema, people with any of the skin disorders/conditions previously listed, people with immunodeficiency disease or use of immunosuppressive medications.
* Any condition which, in the opinion of the investigator, might interfere with study objectives.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa - Iowa City IA
state: Iowa
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Med Ctr
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
References: