Protocol Number: 03-I-0087

Title:

A Phase I/II Clinical Trial of Modified Vaccinia Virus Ankara (MVA) to Evaluate its Safety, Immunogenicity and Protective Efficacy Against Dryvax® (Registered Trademark) Challenge in Vaccinia-Immune Individuals

Number:

03-I-0087

Summary:

This study will test the safety of an experimental vaccine called modified vaccinia virus ankara (MVA) and determine if it confers protection against the smallpox virus (variola). There is an existing vaccine, called Dryvax® (Registered Trademark), which is effective against smallpox; however, this vaccine can cause various side effects, including some that, on rare occasions, can be life-threatening. Dryvax® (Registered Trademark) has not been used in the United States since childhood vaccination was stopped in 1971, and though it is given to certain healthcare and laboratory workers, and some people in the armed forces, it is not recommended for the general population. Both the MVA and Dryvax® (Registered Trademark) vaccines are made using the vaccinia virus, which is closely related to variola.

Healthy normal volunteers between 31 and 60 years of age who have been vaccinated with a smallpox vaccine more than 10 years before entering the study may be eligible for this protocol. Candidates will be screened with a medical history, physical examination, and blood and urine tests, including an HIV test and a pregnancy test for women of childbearing potential.

Participants will receive MVA vaccine or placebo, followed by a dose of Dryvax® (Registered Trademark). The MVA vaccine and placebo are injected into an arm muscle with a needle and syringe. The Dryvax® (Registered Trademark) vaccine is administered with a special forked needle that is poked lightly into the skin of the upper arm, usually 15 times, in a process called scarification. When the vaccine works, a small pus-filled blister forms, followed by a scab and then scarring at the site of the vaccination. The formation of the blister and scab is called a take, indicating that the vaccine is effective and will protect against smallpox for at least a few years. If scarification does not take, it can either mean that the person already has immunity or that the vaccine did not work.

Study participants will be randomly assigned to one of the following dosing groups: 1) one injection of MVA; 2) one injection of placebo; 3) two injections of MVA 4 weeks apart; or 4) two injections of placebo 4 weeks apart. All participants will receive a challenge dose of Dryvax® (Registered Trademark) 12 weeks after their last injection of MVA or placebo to determine if the MVA vaccine has conferred immunity. A take, that occurs in response to the Dryvax® (Registered Trademark) dose indicates lack of prior immunity, and thus tells whether one or two doses of MVA is needed to produce an immune response.

Participants will be observed for at least 1 hour after each injection. They will come to the clinic at least once a week after MVA or placebo injections and at least twice a week after Dryvax® (Registered Trademark) to have the injection site evaluated and photographed. At each visit, participants will be asked how they are feeling and what medications, if any, they are taking. Blood and urine tests will be done according to the following schedule:

- Before each injection;

- 1 week after each injection;

- 4 weeks after the MVA or placebo injections are finished;

- At the time of the Dryvax® (Registered Trademark) dose;

- 4 weeks after the Dryvax® (Registered Trademark) dose;

- 12 weeks after the Dryvax® (Registered Trademark) dose.

Additional laboratory tests may be done between visits if medically necessary.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Follow-up Of Previously Enrolled Subjects Only

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions: Currently Not Provided

Disease Category:

PROTICD

Keywords:

Smallpox

Vaccine

Vaccination

Variola

Adults

Recruitment Keywords:

Healthy Volunteer

HV

Smallpox Vaccine

Conditions:

Healthy

Investigational Drug(s):

Modified Vaccinia Virus Ankara TBC-MVA

Investigational Device(s):

None

Contacts:

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citations:

Stittelaar KJ, Osterhaus AD. MVA: a cuckoo in the vaccine nest? Vaccine. 2001 Jun 14;19(27):V-VI. Review. No abstract available.

Henderson DA, Inglesby TV, Bartlett JG, Ascher MS, Eitzen E, Jahrling PB, Hauer J, Layton M, McDade J,Osterholm MT, O'Toole T, Parker G, Perl T, Russell PK, Tonat K. Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. 1999 Jun 9;281(22):2127-37. Review.

Henderson DA. The looming threat of bioterrorism. Science. 1999 Feb 26;283(5406):1279-82. Review.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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