Effect of Dose, Safety, Tolerability of a New Smallpox Vaccine in Adults Without Previous Smallpox Vaccination

Emergent BioSolutions

Status and phase: Completed; Phase 2

Conditions: Smallpox

Treatments: Biological: Vaccinia virus: ACAM2000 smallpox vaccine; Biological: vaccinia virus (calf lymph): Dryvax

Study type: Interventional

Funder types: Industry

Identifiers

NCT00053495

H-400-005

Details and patient eligibility

About

The purpose of this study is to examine the safety and the effectiveness of a new vaccine for the prevention of the disease, smallpox.

Full description

The objective of this study is to determine the minimum dose of ACAM2000 that is calculated to produce a major cutaneous reaction in at least 90% of a population of healthy adults 18-29 years of age and naïve to smallpox vaccine. Specifically, the objectives of this study are to:

1. Compare the safety and tolerability of four dose levels of ACAM2000 and a standard dose of Dryvax® in healthy adults 18-29 years of age and naïve to smallpox vaccine. Safety and tolerability will be determined by examination of the local cutaneous reaction, adverse events, physical examinations, vital signs, structured interviews, and laboratory analysis.

2. Determine the immunogenicity of four dose levels of ACAM2000 and a standard dose of Dryvax® in healthy adults 18-29 years of age by comparing:

   1. the proportion of subjects at each dose level who develop a major cutaneous reaction;
   2. the proportion of subjects in each treatment group who develop neutralizing antibodies, including the fold-increase in antibody titer between Baseline and Day 30 sera; and the geometric mean vaccinia neutralizing antibody titer on Day 30.

3. Determine the minimum dose of ACAM2000 that is calculated to produce a major cutaneous reaction in at least 90% of a population of healthy adults 18-29 years of age and naïve to smallpox vaccine.

Enrollment: 353 patients

Sex: All

Ages: 18 to 29 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• females must not be pregnant, lactating and must agree to use an effective form of birth control for the 30 days following vaccination or unable to bear children.
• agree to be available for the entire study and agree to comply with all requirements.

Exclusion criteria

• military service prior to 1989.
• history of previous smallpox vaccination.
• children 1 year of age or younger in the household or be in close contact
• smallpox vaccination within ten years
• known or suspected human immunodeficiency virus (HIV) infection, primary immunodeficiency disorder, leukemia, lymphoma, or current radiation treatment or use of immunosuppressive or anti-neoplastic drugs or have a household member or intimate contact with the conditions listed above.
• renal disease
• current or past history of eczema or a household member or direct contact who has eczema.
• known allergy or past allergic reactions to latex gloves or to antibiotics which include neomycin, streptomycin, chlortetracycline, and polymyxin B
• known allergy or past allergic reaction to blood products.
• known allergy to cidofovir or sulfa-containing drugs.
• history of allergic phenomena following smallpox vaccination in the past, including urticaria, erythema multiforme, or Stevens-Johnson syndrome.
• transfusion of blood or treatment with any blood product.
• current or history of drug or alcohol abuse
• inoculation with any other live vaccine or participating in another drug or vaccine trial within 30 days of enrollment.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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353 participants in 5 patient groups

Group 1: ACAM2000 Dose 1

Experimental group

Description:

Participants will receive a single dose of ACAM2000 smallpox vaccine, 1.0x10-8th plaque-forming units (PFU)/mL on Day 0.

Treatment:

Biological: Vaccinia virus: ACAM2000 smallpox vaccine

Group 2: ACAM2000 Dose 2

Experimental group

Description:

Participants will receive a single dose of ACAM2000 smallpox vaccine, 2.0x10-8th plaque-forming units/mL on Day 0.

Treatment:

Biological: Vaccinia virus: ACAM2000 smallpox vaccine

Group 3: ACAM2000 Dose 3

Experimental group

Description:

Participants will receive a single dose of ACAM2000 smallpox vaccine, 1.0x10-7th plaque-forming units/mL on Day 0

Treatment:

Biological: Vaccinia virus: ACAM2000 smallpox vaccine

Group 4: ACAM2000 Dose 4

Experimental group

Description:

Participants received a single dose of ACAM2000 smallpox vaccine, 5.0x10-6th plaque-forming units/mL on Day 0

Treatment:

Biological: Vaccinia virus: ACAM2000 smallpox vaccine

Group 5: Dryvax® Vaccine

Active Comparator group

Description:

Participants will receive a single dose of Dryvax® smallpox vaccine, 1.0x10-8th plaque-forming units/mL on Day 0

Treatment:

Biological: vaccinia virus (calf lymph): Dryvax