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
- Conditions
- Healthy subjects - prevention of smallpox infectionMedDRA version: 8.0Level: PTClassification code 10041197
- Registration Number
- EUCTR2005-001781-14-DE
- Lead Sponsor
- Bavarian Nordic A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 800
All groups
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. Read, signed and dated informed consent document after being advised of the risks and benefits of the study in a language understood by the subject signed, and prior to performance of any study specific procedure.
5. Troponin I within normal institutional limits.
6. White blood cells = 2500/mm3 and = 11,000/ mm3.
7. Absolute neutrophil count (ANC) = 1000/mm3.
8. Negative urine glucose by dipstick or urinalysis.
9. Hemoglobin = LLN.
10. Platelets 100 – 440/nl.
11. Adequate renal function defined as:
a. Serum creatinine without clinically significant findings.
b. Urine protein = 30 mg/dL or none or trace proteinuria (by urinalysis or dip stick).
12. Adequate hepatic function defined as:
a. Total bilirubin = 1.5 x ULN in the absence of other evidence of significant liver disease (healthy subjects without clinical disease with Morbus Meulengracht can be included).
b. AST (SGOT), ALT (SGPT) and alkaline phosphatase without clinically significant findings.
13. 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).
14. Availability for follow-up for the planned duration of the study (26 weeks after last vaccination).
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Pregnant or breast-feeding women.
2. Uncontrolled serious infection i.e. not responding to antimicrobial therapy.
3. History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject.
4. History of or active autoimmune disease. Persons with vitiligo or thyroid disease taking thyroid replacement are not excluded.
5. Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
6. 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.
7. History or clinical manifestation of clinically significant and severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders.
8. Clinically significant mental disorder not adequately controlled by medical treatment.
9. Any condition which might interfere with study objectives or would limit the subject’s ability to complete the study or to be compliant in the opinion of the investigator.
10. 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.
11. History of an immediate family member (father, mother, brother, or sister) who died due to ischemic heart disease before age 50 years.
12. 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.
13. History of intravenous drug abuse.
14. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
15. Known allergy to egg or aminoglycoside (gentamicin).
16. History of anaphylaxis or severe allergic reaction.
17. Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior or after study vaccination.
18. Having received any vaccinations or planned vaccinations with a killed vaccine within14 days prior or after study vaccination.
19. Chronic administration (defined as more than 14 days) of systemic immuno-suppressant drugs during a period starting from six months prior to administration of the vaccine and ending at study conclusion. (Corticosteroid nasal sprays are permissible. Persons who have used topical and inhaled steroids can be enrolled after their therapy is completed).
20. Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy.
21. Administration or planned administration of immunoglobulins and/or any blood products during a period starting from 3 months prior to administration of the vaccine and ending at study conclusion.
22. Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the first dose of the study vaccine, or planned administration of such a drug during the study period.
23. Study personnel.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method