A Phase II Trial to Compare a Liquid-frozen and a Freeze-dried Formulation of IMVAMUNE (MVA-BN®) Smallpox Vaccine in Vaccinia-naïve Healthy Subjects

Bavarian Nordic

Status and phase

Completed

Phase 2

Conditions

Smallpox

Treatments

Biological: LF formulation of IMVAMUNE®

Biological: FD formulation of IMVAMUNE®

Study type

Interventional

Funder types

Industry

Identifiers

NCT01668537

POX-MVA-027

Details and patient eligibility

About

A randomized, double-blind, multicenter Phase II trial to compare the immunogenicity and safety of a liquid-frozen and a freeze-dried formulation of IMVAMUNE (MVA-BN®) smallpox vaccine in vaccinia-naïve healthy subjects

Enrollment

651 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

Male and female subjects, 18-55 years of age
The subject has read, signed and dated informed consent form, having been advised of the risks and benefits of the trial in a language understood by the subject and prior to performance of any trial specific procedures and has signed the Health Insurance Portability and Accountability Act (HIPAA) authorization form
Body Mass Index (BMI) ≥ 18.5 and < 35
Women of childbearing potential (WOCBP) 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 trial, and must avoid becoming pregnant for at least 28 days after the last vaccination. A woman is considered of childbearing potential unless post-menopausal or with a history of hysterectomy. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products)
WOCBP must have a negative serum pregnancy test at screening (SCR) and a negative urine pregnancy test within 24 hours prior to each vaccination
White blood cells ≥ 2500/mm3 and < ULN
Absolute neutrophil count (ANC) within normal limits
Hemoglobin within normal limits
Platelets within normal limits
Adequate renal function defined as a calculated Creatinine Clearance (CrCl) > 60 ml/min as estimated by the Cockcroft-Gault equation:
- For men: (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dl x 72) = CrCl (ml/min)
- For women: multiply the result by 0.85 = CrCl (ml/min)
Adequate hepatic function defined as:
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) in the absence of other evidence of significant liver disease
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase < 1.5 x ULN
Troponin I < 2 x ULN
Electrocardiogram (ECG) without clinically significant 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, two premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia

Exclusion criteria

Typical vaccinia scar
Known or suspected history of smallpox vaccination
History of vaccination with any poxvirus-based vaccine
US Military service before 1991 or after January 2003
Pregnant or breast-feeding women
Uncontrolled serious infection, i.e. not responding to antimicrobial therapy
History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject or would limit the subject's ability to complete the trial in the opinion of the investigator
History of or active autoimmune disease, persons with vitiligo or thyroid disease taking thyroid hormone replacement are not excluded
Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease, diabetes mellitus, moderate to severe kidney impairment
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 must not be vaccinated at the previous tumor site
History or clinical manifestation of clinically significant and severe hematological, pulmonary, central nervous, cardiovascular or gastrointestinal disorders
Clinically significant mental disorder not adequately controlled by medical treatment
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
History of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before the age of 50 years
Twenty 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: This criterion applies only to subjects 20 years of age and older
Active or history of chronic alcohol abuse and/or intravenous and/or nasal drug abuse (within the past 6 months)
Known allergy to IMVAMUNE® vaccine and its constituents, e.g. tris(hydroxymethyl)-amino methane, including known allergy to egg or aminoglycoside (gentamycin)
History of anaphylaxis or severe allergic reaction to any vaccine
Acute disease (illness with or without a fever) at the time of enrollment
Body Temperature ≥ 100.4°F (38.0°C) at the time of enrollment
Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior or after trial vaccination
Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior or after trial vaccination
Chronic systemic administration (defined as more than 14 days) of > 5 mg prednisone (or equivalent)/day or any other immune-modifying drugs during a period starting from three months prior to administration of the vaccine and ending at last physical trial visit (Visit 5)
Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy
Administration or planned administration of immunoglobulins and/or any blood products during a period starting from three months prior to administration of the vaccine and ending at last physical trial visit (Visit 5)
Use of any investigational or non-registered drug or vaccine other than the trial vaccine within 30 days preceding the first dose of the trial vaccine or planned administration of such a drug during the trial period (with the day of the FU call being considered the last day of the trial period).
Trial personnel