Clinical trial NCT01668537: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Smallpox
Lead sponsor: Bavarian Nordic
Sponsor class: INDUSTRY
First posted: 2012-08-20
Enrollment: 651
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: 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


Eligibility criteria: Inclusion criteria

1. Male and female subjects, 18-55 years of age
2. 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
3. Body Mass Index (BMI) ≥ 18.5 and \< 35
4. 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)
5. WOCBP must have a negative serum pregnancy test at screening (SCR) and a negative urine pregnancy test within 24 hours prior to each vaccination
6. White blood cells ≥ 2500/mm3 and \< ULN
7. Absolute neutrophil count (ANC) within normal limits
8. Hemoglobin within normal limits
9. Platelets within normal limits
10. 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)
11. 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
12. Troponin I \< 2 x ULN
13. 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

1. Typical vaccinia scar
2. Known or suspected history of smallpox vaccination
3. History of vaccination with any poxvirus-based vaccine
4. US Military service before 1991 or after January 2003
5. Pregnant or breast-feeding women
6. Uncontrolled serious infection, i.e. not responding to antimicrobial therapy
7. 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
8. History of or active autoimmune disease, persons with vitiligo or thyroid disease taking thyroid hormone replacement are not excluded
9. Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease, diabetes mellitus, moderate to severe kidney impairment
10. 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
11. History or clinical manifestation of clinically significant and severe hematological, pulmonary, central nervous, cardiovascular or gastrointestinal disorders
12. Clinically significant mental disorder not adequately controlled by medical treatment
13. 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
14. 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
15. 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
16. Active or history of chronic alcohol abuse and/or intravenous and/or nasal drug abuse (within the past 6 months)
17. Known allergy to IMVAMUNE® vaccine and its constituents, e.g. tris(hydroxymethyl)-amino methane, including known allergy to egg or aminoglycoside (gentamycin)
18. History of anaphylaxis or severe allergic reaction to any vaccine
19. Acute disease (illness with or without a fever) at the time of enrollment
20. Body Temperature ≥ 100.4°F (38.0°C) at the time of enrollment
21. Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior or after trial vaccination
22. Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior or after trial vaccination
23. 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)
24. Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy
25. 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)
26. 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).
27. Trial personnel

Primary outcomes:
measure: ELISA GMT
timeFrame: Week 6
Secondary outcomes:
measure: Number of Participants With Serious Adverse Events
timeFrame: up to 32 weeks
measure: Number of Participants With Adverse Events of Special Interest (AESI)
timeFrame: up to 32 weeks
measure: Number of Participants With Related Grade >=3 Adverse Events
timeFrame: within 29 days after vaccination
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: within 29 days after vaccination
measure: Number of Participants With Solicited Local Averse Events
timeFrame: 8 days after any vaccination
measure: Number of Participants With Solicited General Adverse Events
timeFrame: within 8 days after any vaccination
measure: ELISA GMTs
timeFrame: within 8 weeks
measure: PRNT GMT
timeFrame: Week 6
measure: PRNT GMTs
timeFrame: within 8 weeks
measure: Percentage of Participants With Seroconversion by ELISA
timeFrame: Week 6
measure: Percentage of Participants With Seroconversion by ELISA
timeFrame: within 8 weeks
measure: Percentage of Participants With Seroconversion by PRNT
timeFrame: Week 6
measure: Percentage of Participants With Seroconversion by PRNT
timeFrame: within 8 weeks
measure: ELISPOT Magnitudes of Response
timeFrame: within 8 weeks
measure: Percentage of Participants With Response by ELISPOT
timeFrame: within 8 weeks
measure: Percentage of Responders by ELISPOT
timeFrame: within 8 weeks
measure: Correlation ELISA vs PRNT Titers
timeFrame: within 8 weeks
Other outcomes:
Locations:
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Lenexa
country: United States
facility: PRA
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Richard N Greenberg, MD
role: PRINCIPAL_INVESTIGATOR
References: