Clinical trial NCT00316524: A Randomized, Double-blind, Placebo-controlled Study on Immunogenicity and Safety of MVA-BN (IMVAMUNE™) Smallpox Vaccine in Healthy Subjects
Official title: A Partially Randomized, Partially Double-blind, Placebo-controlled Phase II Non-inferiority Study to Evaluate Immunogenicity and Safety of One and Two Doses of MVA-BN® (IMVAMUNE™) Smallpox Vaccine in 18-55 Year Old Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Smallpox
Keywords: Smallpox
Vaccination
Prevention
Lead sponsor: Bavarian Nordic
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2006-04-21
Enrollment: 745
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary objective of this study is to evaluate the immune response after a single vaccination of pre-immune subjects compared to two vaccinations in naive subjects.

In addition the study further investigates the cardiac safety profile of MVA-BN® in a healthy population compared to placebo.

Detailed description: The study consists of 4 groups, which receive either MVA-BN once, MVA-BN two times, MVA-BN followed by placebo, or two administrations of placebo.

Eligibility criteria: Inclusion Criteria:

1. Male and female subjects between 18 and 55 years of age.
2. Women must have a negative serum pregnancy test at screening and a negative urine or serum pregnancy test within 24 hours prior to vaccination.
3. Women of childbearing potential must have used an acceptable method of contraception for 30 days prior to the first vaccination, must agree to use an acceptable method of contraception during the study, and must not become pregnant for at least 28 days after the last vaccination. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products.)
4. Lab values without clinically significant findings
5. Electrocardiogram (ECG) without abnormal findings (e.g. any kind of atrioventricular or intraventricular conditions or blocks such as complete left or right bundle branch block, AV-node block, QTc or PR prolongation, premature atrial contractions or other atrial arrhythmia, sustained ventricular arrhythmia, 2 premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia).

Groups 1, 2 and 3 (All vaccinia-naïve subjects) additionally:

1. No history of known or suspected previous smallpox vaccination.
2. No detectable vaccinia scar.

Group 4 (All previously vaccinated subjects) additionally:

1. History of previous smallpox vaccination (documented and/or typical vaccinia scar).
2. Most recent smallpox vaccination ≥ 5 years.

Exclusion Criteria:

1. Uncontrolled serious infection i.e. not responding to antimicrobial therapy.
2. History of or active autoimmune disease. Persons with vitiligo or thyroid disease taking thyroid replacement are not excluded.
3. Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
4. History of malignancy, other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure. Subjects with history of skin cancer at the vaccination site are excluded.
5. History of coronary heart disease, myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, or any other heart condition under the care of a doctor.
6. History of an immediate family member (father, mother, brother, or sister) who died due to ischemic heart disease before age 50 years.
7. 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?usertype=prof) NOTE: This criterion applies only to volunteers 20 years of age and older.
8. History of anaphylaxis or severe allergic reaction.
9. Immune modulatory therapy.
10. History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject.
11. History or clinical manifestation of clinically significant and severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders.

Primary outcomes:
measure: Percentage of Participants With Seroconversion by ELISA
timeFrame: 2 weeks following the last vaccination (Week 6 for Groups 1-3, Week 2 for Group 4)
measure: Number of Participants With ECG Changes
timeFrame: within 2 weeks after each vaccination
measure: Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])
timeFrame: within 32 weeks
Secondary outcomes:
measure: Percentage of Participants With Seroconversion by ELISA
timeFrame: 4 weeks following the last vaccination (Week 8 for Groups 1-3, Week 4 for Group 4)
measure: Percentage of Participants With Seroconversion by PRNT
timeFrame: 2 weeks following the last vaccination (Week 6 for Groups 1-3, Week 2 for Group 4)
measure: Percentage of Participants With Seroconversion by PRNT
timeFrame: 4 weeks following the last vaccination (Week 8 for Groups 1-3, Week 4 for Group 4)
measure: Number of Participants With Related Serious Adverse Events
timeFrame: within 32 weeks
measure: Number of Participants With Solicited Local Adverse Events
timeFrame: within 8 days after any vaccination
measure: Number of Participants With Solicited General Adverse Events
timeFrame: within 8 days after any vaccination
measure: Number of Participants With Related Grade>=3 Adverse Events
timeFrame: within 4 weeks after any vaccination
measure: Number of Participants With Unsolicited Non-serious Adverse Events
timeFrame: within 4 weeks after any vaccination
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Harrison Clinical Research GmbH
state: Bavaria
Study officials:
affiliation: Section of International Medicine & Public Health, Department of Infectious Diseases and Tropical Medicine, Ludwig-Maximilians Unviersity Munich
name: Frank von Sonnenburg, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zitzmann-Roth EM, von Sonnenburg F, de la Motte S, Arndtz-Wiedemann N, von Krempelhuber A, Uebler N, Vollmar J, Virgin G, Chaplin P. Cardiac safety of Modified Vaccinia Ankara for vaccination against smallpox in a young, healthy study population. PLoS One. 2015 Apr 16;10(4):e0122653. doi: 10.1371/journal.pone.0122653. eCollection 2015.