Lyophilized IMVAMUNE® (1x10^8 TCID50) Versus Liquid IMVAMUNE® (1x10^8 TCID50) Administered Subcutaneously and a Lower Dose Liquid IMVAMUNE® (2x10^7 TCID50) Administered Intradermally

NCT00914732 | Completed Phase 2 Results

• 2 other identifiers: 09-0002POX-MVA-029
• Study Type: interventional
• Target: 523
• Locations: 1 country
• Sites: 8

Brief Summary

Due to recent concern of biowarfare and bioterrorism, the US government is making efforts to improve its ability to protect citizens against the smallpox virus. This study will evaluate safety of IMVAMUNE®, an investigational smallpox vaccine, and its ability to stimulate the immune system (the body's defense system). Two vaccine preparations have the same name but one is a liquid and one is a powder that has liquid added just before it is given. The vaccine that comes as a liquid will be injected (given as a shot) just under the skin (subcutaneously) or injected between the layers of the skin (intradermally). The powder formulation is only injected just under the skin. Approximately 495 adults, age 18 older born after 1971, which have not had smallpox vaccine before, may participate in the study for about 7 months.

Conditions

Smallpox

Keywords

IMVAMUNE®, smallpox, vaccine

Outcome Measures

Primary Outcomes (5)

• Geometric Mean Titer (GMT) Based on Vaccinia-specific Individual Peak Plaque Reduction Neutralization Titers (PRNT) Following 2 Doses of IMVAMUNE® Lyophilized Versus Following 2 Doses of IMVAMUNE® Liquid Administered Subcutaneously, ITT Population

  Blood was collected from participants for testing in the PRNT assay with vaccinia-Western Reserve (replicating vaccinia) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 7.5 (half the lower limit of detection) for analysis.

  Days 14, 28 and 180 after 2nd vaccination

• GMT Based on Vaccinia-specific Individual Peak PRNT Following 2 Doses of IMVAMUNE® Lyophilized Versus Following 2 Doses of IMVAMUNE® Liquid Administered Subcutaneously, Per Protocol Population

  Blood was collected from participants for testing in the PRNT assay with vaccinia-Western Reserve (replicating vaccinia) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 7.5 (half the lower limit of detection) for analysis.

  Days 14, 28 and 180 after 2nd vaccination

• GMT Based on Vaccinia-specific Individual Peak PRNT, Following 2 (Lower) Doses Liquid IMVAMUNE® Administered Intradermally Versus 2 (Higher) Doses of Liquid IMVAMUNE® Administered Subcutaneously, ITT Population

  Blood was collected from participants for testing in the PRNT assay with vaccinia-Western Reserve (replicating vaccinia) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 7.5 (half the lower limit of detection) for analysis.

  Days 14, 28 and 180 after 2nd vaccination

• GMT Based on Vaccinia-specific Individual Peak PRNT, Following 2 (Lower) Doses Liquid IMVAMUNE® Administered Intradermally Versus 2 (Higher) Doses of Liquid IMVAMUNE® Administered Subcutaneously, Per Protocol Population

  Blood was collected from participants for testing in the PRNT assay with vaccinia-Western Reserve (replicating vaccinia) as the assay antigen. The geometric mean titers were calculated for each timepoint as well as for the peak titer after second vaccination. Titer values below limit of detection were replaced by 7.5 (half the lower limit of detection) for analysis.

  Days 14, 28 and 180 after 2nd vaccination

• Number of Participants Reporting Serious Adverse Events Associated With IMVAMUNE® Vaccination

  An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Those SAEs considered associated are those with a known temporal relationship, or the event is known to occur in association with study product or with a product in a similar class of study products AND no alternate etiology is identified.

  Day 0 through 180 days after second vaccination

Secondary Outcomes (5)

• Number of Participants Assessed With Grade 3 and 4 Laboratory Toxicities Associated With IMVAMUNE®.

  Days 0, 14 and 42

• GMT Based on Vaccinia-specific Individual Peak ELISA Titers, Following 2 Doses (Lower) Liquid Formulation IMVAMUNE® Administered Intradermally Versus That Obtained Following 2 Doses IMVAMUNE® Liquid Formulation Administered Subcutaneously, ITT Population

  Days 14, 28 and 180 after 2nd vaccination

• GMT Based on Vaccinia-specific Individual Peak ELISA Titers, Following 2 Doses (Lower) Liquid Formulation IMVAMUNE® Administered Intradermally Versus That Obtained Following 2 Doses IMVAMUNE® Liquid Formulation Subcutaneously, Per Protocol Population

  Days 14, 28 and 180 after second vaccination

• GMT Based on Vaccinia-specific Individual Peak ELISA Titers Following 2 Doses of IMVAMUNE® Lyophilized Formulation Versus That Obtained Following 2 Doses of IMVAMUNE® Liquid Formulation Subcutaneously, ITT Population.

  Days 14, 28 and 180 after 2nd vaccination.

• GMT Based on Vaccinia-specific Individual Peak ELISA Titers Following 2 Doses of IMVAMUNE® Lyophilized Formulation Versus That Obtained Following 2 Doses of IMVAMUNE® Liquid Formulation Subcutaneously, Per Protocol Population.

  Days 14, 28 and 180 after 2nd vaccination.

Study Arms (3)

Group B, liquid, subcutaneous

EXPERIMENTAL

Group B: 165 subjects will receive a 2 dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL per dose) liquid formulation by the subcutaneous route on Day 0 and 28.

Biological: MVA Smallpox Vaccine

Group C, liquid, intradermal

EXPERIMENTAL

Group C: 165 subjects will receive a 2 dose regimen of IMVAMUNE® (2x10\^7 TCID50/0.1mL per dose) liquid formulation by the intradermal route on Day 0 and 28.

Biological: MVA Smallpox Vaccine

Group A, lyophilized, subcutaneous

EXPERIMENTAL

Group A: 165 subjects will receive a 2 dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL per dose) lyophilized formulation by the subcutaneous route on Day 0 and 28.

Biological: MVA Smallpox Vaccine

Interventions

MVA Smallpox Vaccine BIOLOGICAL

Vaccinia vaccine liquid formulation delivered by subcutaneous (SC) route at 1x10\^8 TCID50 per 0.5 mL dose on Days 0 and 28.

Group B, liquid, subcutaneous

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.
• Read, signed, and dated informed consent document.
• Available for follow-up for the planned duration of the study (6 months 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 28 days following the last vaccination:
• A woman is considered of childbearing potential unless post-menopausal (greater than or equal to 1 year) or surgically sterilized (tubal ligation, bilateral oophorectomy, or hysterectomy).
• Acceptable contraception methods are restricted to effective devices \[intrauterine devices (IUD)s, NuvaRing®\] or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, abstinence from sexual intercourse with men (vaginal penetration by a penis, coitus), and monogamous relationship with a vasectomized partner.
• 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 is defined as a serum creatinine not exceeding the institution's upper limit of normal.
• Electrocardiogram (ECG) in absence of clinical significance (e.g., complete left or right bundle branch block, incomplete left bundle branch block or sustained ventricular arrhythmia, or 2 premature ventricular contraction's (PVC)'s in a row, or sympathetic tonus (ST) elevation consistent with ischemia).
• The following blood parameters:

You may not qualify if:

• History of immunodeficiency
• Typical vaccinia scar
• Known or suspected history of smallpox vaccination including Modified Vaccinia Ankara (MVA) alone or as a vector as well as other investigational smallpox vaccine
• 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
• a. 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
• Systolic blood pressure greater than or equal to 150 mmHg or diastolic blood pressure greater than or equal to 100 mmHg
• 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://hp2010.nhlbihin.net/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
• High-dose steroid use for greater than 2 weeks duration within three months prior to vaccination and current use of immunosuppressive medication
• Corticosteroid nasal sprays are permissible

Sponsors & Collaborators

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

Study Sites (8)

Emory Vaccine Center - The Hope Clinic

Decatur, Georgia, 30030-1705, United States

Location

University of Iowa - Vaccine Research & Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

University of Maryland School of Medicine - Center for Vaccine Development - Baltimore

Baltimore, Maryland, 21201-1509, United States

Location

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Vanderbilt University Hospital - Pediatric Clinical Research

Nashville, Tennessee, 37232-0004, United States

Location

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, 77030-3411, United States

Location

Group Health Research Institute - Seattle

Seattle, Washington, 98101-1466, United States

Location

The University of Washington - Virology Research Clinic

Seattle, Washington, 98104-2433, United States

Location

Related Publications (1)

• Frey SE, Stapleton JT, Ballas ZK, Rasmussen WL, Kaufman TM, Blevins TP, Jensen TL, Davies DH, Tary-Lehmann M, Chaplin P, Hill H, Goll JB; DMID 09-0002 MVA Vaccine Study Group. Human Antibody Responses Following Vaccinia Immunization Using Protein Microarrays and Correlation With Cell-Mediated Immunity and Antibody-Dependent Cellular Cytotoxicity Responses. J Infect Dis. 2021 Oct 28;224(8):1372-1382. doi: 10.1093/infdis/jiab111.

  PMID: 33675226 DERIVED

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 School

sharon.frey@health.slu.edu

314-977-5500

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2009
• First Posted: June 5, 2009
• Study Start: February 1, 2010
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: February 3, 2021
• Results First Posted: January 12, 2021

Record last verified: 2011-01

Locations

US (8)