The purpose of this study is to evaluate an investigational smallpox vaccine, called IMVAMUNE®, with respect to safety and immune (body's defense system) response. Participants will include healthy adults, age 18 or older born after 1971, who have not had smallpox vaccine before. Participants were originally assigned to 1 of 5 groups. In July 2007, a hold was placed on the Dryvax® groups and the study was modified. Participants, will be assigned by chance to one of 3 groups to be vaccinated twice with IMVAMUNE® vaccine or placebo (inactive substance) in Groups A and B, or to receive a single vaccination with IMVAMUNE® or placebo in Group F. Participants will complete a memory aid (diary) for 15 days following vaccination. Blood samples will be collected. Participants may participate for up to 425 days.
The study will evaluate the IMVAMUNE® smallpox vaccine with respect to safety and optimization of immune responses by different vaccination regimens in vaccinia-naïve adults. Study participants must be age 18 and older and born after 1971. Originally, participants were planned to be randomly assigned to 1 of 5 groups to be immunized twice with IMVAMUNE® vaccine or placebo subcutaneously in Groups A and B, or Dryvax® or placebo by scarification in Group C or both IMVAMUNE® and Dryvax® or 2 placebos in Groups D and Group E. In July 2007, enrollment was halted at the request of Center for Biologics Evaluation and Research (CBER). At that time, enrollment included zero subjects in Group A, 2 subjects in Group B, 8 subjects in Group C, 6 subjects in Group D, and 4 subjects in Group E. CBER placed an official hold on the enrollment into the Groups that would administer Dryvax®, i.e., Groups C, D and E. Subjects previously enrolled into Groups C, D, and E will be followed according to the protocol. The protocol has been modified as follows. Participants will be randomly assigned to 1 of 3 groups to be immunized twice with IMVAMUNE® vaccine or placebo subcutaneously in Groups A and B, or to receive a single immunization with IMVAMUNE® or placebo subcutaneously in Group F. (NOTE: Group B will contain two additional participants that were enrolled prior to modification.) Group A will receive IMVAMUNE® vaccine or placebo on Days 0 and 7. Group B will receive IMVAMUNE® vaccine or placebo on Days 0 and 28. Group F will receive a single dose of IMVAMUNE® at Day 0. All participants will complete a memory aid for 15 days following each vaccination. Groups C, D, and E will have the appropriate reactogenicity information collected until the vaccination lesion, if present is well dried. Adverse events will be collected for 28 days after each vaccination. Specimens will be collected for immunologic assays at the noted clinic visits, as well as 1 year post last vaccination. Serious adverse events will be collected throughout the study period. The primary safety objective is to evaluate the safety of IMVAMUNE® given as a single dose, IMVAMUNE® given in a 2 dose prime-boost regimen at Day 0 and 7 or Day 0 and 28, IMVAMUNE® followed by a boost with Dryvax®, and IMVAMUNE® given simultaneously with Dryvax®. The primary immunogenicity objective is to determine if the Geometric Mean Titer (GMT) of neutralizing antibody \[using Modified Vaccinia Ankara (MVA) as the target antigen\] among subjects receiving a regimen of 2 doses of IMVAMUNE® (1×10\^8, Days 0 and 7, Group A) is non-inferior to that among subjects receiving 2 doses of IMVAMUNE® (1×10\^8, Days 0 and 28, Group B) at Day 14 following the 2nd dose. The secondary immunogenicity objective is to determine if the GMT, as assessed by enzyme linked immunosorbent assay (ELISA) (using MVA as the target antigen), among subjects receiving a regimen of 2 doses of IMVAMUNE® (1×10\^8, Days 0 and 7, Group A) is non-inferior to that among subjects receiving 2 doses of IMVAMUNE® (1×10\^8, Days 0 and 28, Group B) at Day 14 following the 2nd dose. The tertiary immunogenicity objective is to characterize the kinetics, magnitude, and duration of cellular and humoral immune responses to IMVAMUNE® alone or IMVAMUNE® as a prime followed by a boost with IMVAMUNE® or Dryvax®, or Dryvax® alone.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
226
Dryvax® Vaccinia Vaccine (\~10\^5 \[plaque forming units (pfu)/dose\] given via scarification, titer 10\^8 pfu per mL after reconstitution).
IMVAMUNE® Vaccinia Vaccine delivered by subcutaneous (SC) route at titer 1X10\^8 Tissue Culture Infections Dose50 per 0.5 mL dose.
0.9 percent (weight/volume) sodium chloride injection, United States Pharmacopeia \[Sterile Saline Placebo (SSP)\].
Physiologic normal saline for injection.
University of Iowa - Vaccine Research and Education Unit
Iowa City, Iowa, United States
University of Maryland, School of Medicine, Center for Vaccine Development and Global Health
Baltimore, Maryland, United States
Saint Louis University Center for Vaccine Development
St Louis, Missouri, United States
University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases
Rochester, New York, United States
Duke Translational Medicine Institute - Clinical Vaccine Unit
Durham, North Carolina, United States
Case Western Reserve University - John T. Carey Special Immunology Unit
Cleveland, Ohio, United States
University of Texas Medical Branch - Pediatrics - Infectious Diseases and Immunology - Galveston
Galveston, Texas, United States
Geometric Mean Titer (GMT) of Bavarian Nordic's (BN) Plaque Reduction Neutralizing Antibody Titer (PRNT) Assay in Groups A and B
Geometric mean of titers collected 14 days after the second vaccination.
Time frame: Day 14 after the second vaccination
GMT of Saint Louis University's (SLU) PRNT Assay in Group A and Group B
Geometric mean of titers collected 14 days after the second vaccination.
Time frame: Day 14 after the second vaccination
Frequency of Serious Adverse Events (SAEs)
The number of participants who experienced at least one SAE throughout the course of the study. A SAE is defined as an AE meeting one of the following conditions: * Death during the study period (from first vaccine until end of surveillance period) * Life-threatening (defined as a participant at immediate risk of death at the time of the event) * Requires inpatient hospitalization or prolongation of existing hospitalization during the period of protocol-defined surveillance * Results in a congenital anomaly or birth defect * Results in a persistent or significant disability/incapacity * Severe adverse event associated with study product
Time frame: Day 0 after first vaccination to study completion through Day 365 after last vaccination
Frequency of Non-Serious AEs
The number of participants who experienced at least one unsolicited non-serious AE of any severity from Day 0 after the first vaccination to 28 days after the last vaccination.
Time frame: Day 0 after first vaccination through Day 28 after last vaccination
Frequency of Local Solicited Reactogenicity AEs for Groups A, B, and D and Placebo A, B, and D
Local solicited reactogenicity AEs were collected daily for 15 days post each vaccination using a memory aid. Local events include pain at vaccination site, itchiness at vaccination site, rash at vaccination site underarm pain, underarm swelling, erythema, and induration. Erythema and induration at the vaccination site were measured in millimeters; the remaining events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Time frame: Day 0 through Day 15 after first vaccination; Day 0 through Day 15 after second vaccination
Frequency of Local Solicited Reactogenicity AEs for Groups C and F and Placebo F
Local solicited reactogenicity AEs were collected daily for 15 days post vaccination using a memory aid. Local events include pain at vaccination site, itchiness at vaccination site, rash at vaccination site underarm pain, underarm swelling, erythema, and induration. Erythema and induration at the vaccination site were measured in millimeters; the remaining events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Time frame: Day 0 through Day 15 after first vaccination
Frequency of Local Solicited Reactogenicity AEs for Group E and Placebo E
Local solicited reactogenicity AEs were collected daily for 15 days post vaccination using a memory aid. Results are reported by vaccination site (MVA Vaccination or Dryvax Vaccination). Local events included pain at vaccination site, itchiness at vaccination site, rash at vaccination site underarm pain, underarm swelling, erythema, and induration. Erythema and induration at the vaccination site were measured in millimeters; the remaining events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Time frame: Day 0 through Day 15 after first vaccination
Frequency of Systemic Solicited Reactogenicity AEs for Groups A, B, and D and Placebo A, B, and D
Systemic solicited reactogenicity AEs were collected daily for 15 days post each vaccination using a memory aid. Systemic events included muscle aches, chills, headache, nausea, feeling tired, change in appetite, joint pain, and elevated oral temperature. Events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Time frame: Day 0 through Day 15 after first vaccination; Day 0 through Day 15 after second vaccination
Frequency of Systemic Solicited Reactogenicity AEs for Groups C, E, and F and Placebo E and F
Systemic solicited reactogenicity AEs were collected daily for 15 days post vaccination using a memory aid. Systemic events included muscle aches, chills, headache, nausea, feeling tired, change in appetite, joint pain, and elevated oral temperature. Events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Time frame: Day 0 through Day 15 after first vaccination
GMT of BN Enzyme Linked Immunosorbent Assay (ELISA) in Groups A and B
Geometric mean of titers collected 14 days after the second vaccination.
Time frame: Day 14 after the second vaccination
GMT of SLU ELISA in Groups A and B
Geometric mean of titers collected 14 days after the second vaccination.
Time frame: Day 14 after the second vaccination
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