High Dose IMVAMUNE® in Vaccinia-Naive Individuals

NCT00879762 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 08-0040
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research is to compare the ability of a new investigational smallpox vaccine called IMVAMUNE® to produce a strong immune response against smallpox disease if given as one single, higher dose compared with two lower doses given one month apart. Another purpose of the study is to see how quickly someone might be protected against smallpox. Volunteers will be vaccinia-naïve adults age 18 and older (born after 1971) divided into 2 groups. Volunteers in Group A will receive a high dose of vaccine given in 2 shots on day 0 followed by a placebo (inactive substance) shot on day 28. Group B will receive the standard dose of vaccine and placebo given in 2 shots on day 0 followed by a standard dose shot on Day 28. Study participation will include 10 planned study visits over approximately 7 months.

Conditions

Smallpox

Keywords

IMVAMUNE®; smallpox; vaccine

Outcome Measures

Primary Outcomes (7)

• Time to Seroconversion After One Vaccination Using Bavarian Nordic's (BN) Enzyme Linked Immunosorbent Assay (ELISA) in the Intent-to-Treat (ITT) Population

  Seroconversion is defined as a titer \>= 50 or as a 2-fold or greater increase in titer from baseline if pre-vaccination titer was \>= 50. Participants who did not seroconvert during the study were analyzed as right censored at the last sample collection date. Samples collected after the second vaccination were also analyzed as right censored.

  Days 0, 4, 8, 14, 21, and 28 after first vaccination

• Time to Seroconversion After One Vaccination Using BN ELISA in the Per Protocol Population

  Seroconversion is defined as a titer \>= 50 or as a 2-fold or greater increase in titer from baseline if pre-vaccination titer was \>= 50. Participants who did not seroconvert during the study were analyzed as right censored at the last sample collection date. Samples collected after the second vaccination were also analyzed as right censored.

  Days 0, 4, 8, 14, 21, and 28 after first vaccination

• Frequency of Serious Adverse Events (SAEs) Related to Vaccination

  The number of participants who experienced at least one SAE throughout the course of the study that was deemed related to the study vaccination. 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 180 after second vaccination (Day 208 after first vaccination)

• Frequency of Non-Serious AEs Related to Vaccination

  The number of participants who experienced at least one unsolicited non-serious AE of any severity from Day 0 to 28 days post second vaccination (56 days post first vaccination) that was deemed related to the study vaccination.

  Day 0 after first vaccination to Day 28 after second vaccination (Day 56 after first vaccination)

• Frequency of Local Solicited Reactogenicity AEs for Subjective Symptoms

  Local solicited reactogenicity AEs were collected daily for 15 days post each vaccination using a memory aid. Local subjective events included pain at injection site, itchiness at injection site, underarm pain, and underarm swelling and were graded on a 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 (Day 28 through Day 43 after first vaccination)

• Frequency of Local Solicited Reactogenicity AEs for Measured Symptoms

  Local solicited reactogenicity AEs were collected daily for 15 days post each vaccination using a memory aid. Local measured events included erythema and induration at the vaccination site and were measured in millimeters.

  Day 0 through Day 15 after first vaccination; Day 0 through Day 15 after second vaccination (Day 28 through Day 43 after first vaccination)

• Frequency of Systemic Solicited Reactogenicity AEs

  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 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 (Day 28 through Day 43 after first vaccination)

Secondary Outcomes (2)

• Peak Titer of Saint Louis University's (SLU) Plaque Reduction Neutralizing Antibody Titer (PRNT) Assay After First Vaccination in the ITT Population

  Days 4, 8, 14, 21, and 28 after first vaccination

• Peak Titer of SLU PRNT Assay After First Vaccination in the Per Protocol Population

  Days 4, 8, 14, 21, and 28 after first vaccination

Study Arms (2)

Group A: High Dose

EXPERIMENTAL

Single high dose of IMVAMUNE® (5x10\^8 TCID50, consisting of two 0.5 mL injections) vaccine on Day 0 and a single saline placebo dose (single 0.5 mL injection) on Day 28 to match the two dose regimen of Group B.

Biological: MVA Smallpox Vaccine; Other: Placebo

Group B: Standard Dose

ACTIVE COMPARATOR

Standard two dose regimen of IMVAMUNE® (1x10\^8 TCID50) vaccine on Day 0 (consisting of 0.5 mL injection of vaccine and 0.5 mL injection of saline placebo) and Day 28 (single 0.5 mL injection of vaccine).

Biological: MVA Smallpox Vaccine; Other: Placebo

Interventions

MVA Smallpox Vaccine BIOLOGICAL

IMVAMUNE® Vaccinia Vaccine, undiluted, delivered by subcutaneous route on Day 0 at high dose 5×10\^8 TCID50 (5×10\^8 TCID50 per 1.0 mL dose - administered as 2 x 0.5 mL.

Group A: High Dose; Group B: Standard Dose

Placebo OTHER

0.5 mL injection of saline placebo administered with vaccine on Day 0 (Group B) or single saline placebo dose (single 0.5 mL injection) on Day 28 (Group A).

Group A: High Dose; Group B: Standard Dose

Eligibility Criteria

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

Sponsors & Collaborators

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

Study Sites (2)

University of Iowa - Vaccine Research and Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

Saint Louis University Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2009
• First Posted: April 10, 2009
• Study Start: May 29, 2009
• Primary Completion: March 9, 2011
• Study Completion: March 9, 2011
• Last Updated: June 13, 2025
• Results First Posted: June 13, 2025

Record last verified: 2012-01-26

Locations

US (2)