MVA Post-Event: Administration Timing and Boost Study

NCT00437021 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 06-0012
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Smallpox

Keywords

IMVAMUNE®; smallpox; vaccine

Outcome Measures

Primary Outcomes (9)

• 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.

  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.

  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

  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.

  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).

  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).

  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).

  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).

  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).

  Day 0 through Day 15 after first vaccination

Secondary Outcomes (2)

• GMT of BN Enzyme Linked Immunosorbent Assay (ELISA) in Groups A and B

  Day 14 after the second vaccination

• GMT of SLU ELISA in Groups A and B

  Day 14 after the second vaccination

Study Arms (6)

Group A

EXPERIMENTAL

Standard dose IMVAMUNE® vaccine or placebo on Days 0 and 7.

Biological: MVA Smallpox Vaccine; Other: Placebo

Group B

EXPERIMENTAL

Standard dose IMVAMUNE® vaccine or placebo on Days 0 and 28.

Biological: MVA Smallpox Vaccine; Other: Placebo

Group C

ACTIVE COMPARATOR

Dryvax® vaccine or placebo on Day 0. This arm was discontinued from original protocol. Subjects already enrolled in this group will continue follow-up per protocol.

Biological: Live vaccinia virus vaccine; Other: Placebo

Group D

EXPERIMENTAL

Standard dose IMVAMUNE® vaccine or placebo on Day 0 and Dryvax® vaccine or placebo on Day 7. This arm was discontinued from original protocol. Subjects already enrolled in this group will continue follow-up per protocol.

Biological: Live vaccinia virus vaccine; Biological: MVA Smallpox Vaccine; Other: Placebo

Group E

EXPERIMENTAL

Dryvax® vaccine and standard dose IMVAMUNE® vaccine or 2 placebos on Day 0. This arm was discontinued from original protocol. Subjects already enrolled in this group will continue follow-up per protocol.

Biological: Live vaccinia virus vaccine; Biological: MVA Smallpox Vaccine; Other: Placebo

Group F

EXPERIMENTAL

Standard dose IMVAMUNE® vaccine or placebo on Day 0.

Biological: MVA Smallpox Vaccine; Other: Placebo

Interventions

Live vaccinia virus vaccine BIOLOGICAL

Dryvax® Vaccinia Vaccine (\~10\^5 \[plaque forming units (pfu)/dose\] given via scarification, titer 10\^8 pfu per mL after reconstitution).

Group C; Group D; Group E

MVA Smallpox Vaccine BIOLOGICAL

IMVAMUNE® Vaccinia Vaccine delivered by subcutaneous (SC) route at titer 1X10\^8 Tissue Culture Infections Dose50 per 0.5 mL dose.

Group A; Group B; Group D; Group E; Group F

Placebo OTHER

0.9 percent (weight/volume) sodium chloride injection, United States Pharmacopeia \[Sterile Saline Placebo (SSP)\].

Group A; Group B; Group D; Group E; Group F

Eligibility Criteria

• Age: 18 Years - 38 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• At least 18 years of age and born after 1971 -Never received smallpox vaccination -Read, signed, and dated informed consent document -Available for follow-up for the planned duration of the study (one year after last immunization) -Acceptable medical history by screening evaluation and limited physical assessment -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 use acceptable contraception, and not become pregnant for the duration of the study a. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized b. Acceptable contraception methods are restricted to effective devices (e.g., Intrauterine Devices (IUD)s, NuvaRing®) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, and abstinence from sexual intercourse with men (vaginal penetration by a penis, coitus) c. Women who are not sexually active must agree to use one of the acceptable contraception methods if they are of childbearing potential -Negative enzyme linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) -Alanine aminotransferase (ALT) \<1.25 times institutional upper limit of normal -Negative hepatitis B surface antigen and negative antibody to hepatitis C virus -Negative urine glucose and urine protein \<1 plus by dipstick or urinalysis Adequate renal function defined as a serum creatinine equal to or less than the institutional upper limit of normal by gender; and urine protein \<30 mg/dL or trace proteinuria (by urinalysis or dip stick). -Electrocardiogram (ECG) in absence of clinical significance (e.g., complete left or right bundle branch block, incomplete left bundle branch block or sustained ventricular arrythmia, or two premature ventricular contractions (PVC's) in a row, or sympathetic tonus (ST) elevation consistent with ischemia) -Complete blood count (CBC): Hemoglobin equal to or above the lower limit of institutional normal; White blood cells greater than or equal to 3200 /mm\^3 and equal to or below the upper limit of institutional normal Platelets equal to or above the lower limit of institutional normal -Weight: greater than or equal to 110 pounds

You may not qualify if:

• History of immunodeficiency -Typical vaccinia scar -Known or suspected history of smallpox vaccination -Military service prior to 1991 or after January 2003 -Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease, diabetes mellitus, or moderate to severe kidney impairment -Malignancy not including squamous cell skin cancer or basal cell skin cancer unless at the vaccination site or history of skin cancer at the vaccination site -Active autoimmune disease Persons with vitiligo or thyroid disease (e.g., taking thyroid hormone replacement) are not excluded. -History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor -Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's risk assessment tool (http://hin.nhlbi.nih.gov/atpiii/calculator.asp) -NOTE that this criterion applies only to subjects 20 years of age and older AND only if at least one of the following apply: a. have smoked a cigarette in the past month, and/or b. have hypertension (defined as systolic blood pressure \>140 mm Hg) or are on antihypertensive medication, and/or c. have a family history of coronary heart disease in male first-degree relative (father or brother) \<55 years of age or a female first-degree relative (mother or sister) \<65 years of age. -Current use of immunosuppressive medication a. Corticosteroid nasal sprays are permissible b. Persons who are using a topical steroid can be enrolled after their therapy is completed c. Inhaled steroids for asthma are not permissible -Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol -Any history of illegal injection drug use -Receipt of inactivated vaccine 14 days prior to vaccination -Receipt of live attenuated vaccine within 30 days prior to vaccination -Use of experimental agent within 30 days prior to vaccination -Receipt of blood products or immunoglobulin within six months prior to vaccination -Donation of a unit of blood within 56 days prior to vaccination or for the duration of the study -Acute febrile illness (greater than or equal to 100.5 degrees F) on the day of vaccination -Pregnant or lactating women -Eczema of any degree or history of eczema -People with atopic dermatitis, chronic exfoliative skin disorders/conditions, current Varicella zoster, or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2×2 cm -Any condition that, in the opinion of the investigator, might interfere with study objectives -Known allergy to IMVAMUNE® vaccine -Known allergy to egg or aminoglycoside -Study personnel

Sponsors & Collaborators

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

Study Sites (7)

University of Iowa - Vaccine Research and Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

University of Maryland, School of Medicine, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201-1509, United States

Location

Saint Louis University Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases

Rochester, New York, 14642-0001, United States

Location

Duke Translational Medicine Institute - Clinical Vaccine Unit

Durham, North Carolina, 27704-2120, United States

Location

Case Western Reserve University - John T. Carey Special Immunology Unit

Cleveland, Ohio, 44106-3808, United States

Location

University of Texas Medical Branch - Pediatrics - Infectious Diseases and Immunology - Galveston

Galveston, Texas, 77555-5302, United States

Location

Related Publications (1)

• Frey SE, Winokur PL, Salata RA, El-Kamary SS, Turley CB, Walter EB Jr, Hay CM, Newman FK, Hill HR, Zhang Y, Chaplin P, Tary-Lehmann M, Belshe RB. Safety and immunogenicity of IMVAMUNE(R) smallpox vaccine using different strategies for a post event scenario. Vaccine. 2013 Jun 24;31(29):3025-33. doi: 10.1016/j.vaccine.2013.04.050. Epub 2013 May 9.

  PMID: 23664987 RESULT

MeSH Terms

Conditions

Smallpox

Interventions

smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Sharon E. Frey, M.D.
• Organization: Saint Louis University Medical Center

sharon.frey@health.slu.edu

315-977-5500

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2007
• First Posted: February 19, 2007
• Study Start: April 16, 2007
• Primary Completion: April 21, 2009
• Study Completion: April 21, 2009
• Last Updated: September 19, 2025
• Results First Posted: September 19, 2025

Record last verified: 2010-03-08

Locations

US (7)