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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bavarian Nordic
ClinicalTrials.gov Identifier:
NCT01668537
First received: August 14, 2012
Last updated: November 13, 2013
Last verified: July 2013
  Purpose

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


Condition Intervention Phase
Smallpox
Biological: LF formulation of IMVAMUNE®
Biological: FD formulation of IMVAMUNE®
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Bavarian Nordic:

Primary Outcome Measures:
  • Geometric Mean Titers (GMTs) measured by ELISA [ Time Frame: Visit 4 (Week 6) ] [ Designated as safety issue: No ]
    Geometric Mean Titers (GMTs) after two IMVAMUNE® FD or IMVAMUNE® LF vaccinations measured by vaccinia-specific ELISA at trial Visit 4 (Week 6).


Secondary Outcome Measures:
  • Serious Adverse Events [ Time Frame: Any Time ] [ Designated as safety issue: Yes ]
    Occurrence, relationship to the trial vaccines and intensity of any Serious Adverse Event (SAE).

  • Adverse Events of Special Interests [ Time Frame: Any Time ] [ Designated as safety issue: Yes ]
    Occurrence, relationship to the trial vaccines and intensity of any Adverse Event of Special Interest (AESI)

  • Grade 3 or 4 Adverse Events [ Time Frame: 28 days after vaccination ] [ Designated as safety issue: Yes ]
    Occurrence of any Grade 3 or 4 Adverse Events (AEs) probably, possibly or definitely related to the trial vaccines within 28 days after each vaccination.

  • Unsolicited non-serious Adverse Events [ Time Frame: 28 days after vaccination ] [ Designated as safety issue: Yes ]
    Occurrence, relationship to the trial vaccines and intensity of unsolicited non-serious AEs within 28 days after each vaccination

  • Solicited local Averse Events [ Time Frame: 8 days after each vaccination ] [ Designated as safety issue: Yes ]
    Occurrence, intensity and duration of solicited local AEs (redness, swelling, induration, pruritus and pain) during the 8-day period (day of vaccination and the following 7 days) after each vaccination

  • Solicited general AEs [ Time Frame: 8 days after each vaccination ] [ Designated as safety issue: Yes ]
    Occurrence, relationship to the trial vaccines, intensity and duration of solicited general AEs (pyrexia, headache, myalgia, nausea, fatigue and chills) during the 8-day period (day of vaccination and the following 7 days) after each vaccination

  • GMTs measured by PRNT [ Time Frame: Visit 4 (Week 6) ] [ Designated as safety issue: No ]
    GMTs after two IMVAMUNE® FD or IMVAMUNE® LF vaccinations measured by vaccinia-specific PRNT at trial Visit 4 (Week 6).

  • Seroconversion measured by ELISA [ Time Frame: Visit 4 (week 6) ] [ Designated as safety issue: No ]
    Seroconversion rates after two IMVAMUNE® vaccinations measured by vaccinia-specific ELISA at trial Visit 4 (Week 6).

  • Seroconversion measured by PRNT [ Time Frame: Visit 4 (week 6) ] [ Designated as safety issue: No ]
    Seroconversion rates after two IMVAMUNE® vaccinations measured by vaccinia-specific PRNT at trial Visit 4 (Week 6).

  • GMTs and Seroconversion rates [ Time Frame: Any time ] [ Designated as safety issue: No ]
    GMTs and Seroconversion rates at all other immunogenicity sampling points as determined by vaccinia-specific ELISA and PRNT

  • Response rates and magnitudes of response of IFN-γ producing T cells [ Time Frame: Any time ] [ Designated as safety issue: No ]
    Response rates and magnitudes of response of IFN-γ producing T cells measured by vaccinia-specific Enzyme Linked Immuno Spot Technique (ELISPOT)

  • Pearson Correlation Coefficient [ Time Frame: Week 4, 6 and 8 ] [ Designated as safety issue: No ]
    Pearson Correlation Coefficient between the ELISA titers and the PRNT titers at weeks 4, 6 and 8 based on the log10 transformed titer values


Estimated Enrollment: 650
Study Start Date: March 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
LF formulation of IMVAMUNE® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
Biological: LF formulation of IMVAMUNE®
Experimental: Group 2
FD formulation of IMVAMUNE® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
Biological: FD formulation of IMVAMUNE®

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01668537

Locations
United States, Florida
Miami Research Associates
South Miami, Florida, United States, 33143
United States, Kansas
PRA
Lenexa, Kansas, United States, 66219
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
Sponsors and Collaborators
Bavarian Nordic
Investigators
Principal Investigator: Richard N Greenberg, MD University of Kentucky
  More Information

No publications provided

Responsible Party: Bavarian Nordic
ClinicalTrials.gov Identifier: NCT01668537     History of Changes
Other Study ID Numbers: POX-MVA-027
Study First Received: August 14, 2012
Last Updated: November 13, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Smallpox
Vaccinia
Poxviridae Infections
DNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on September 14, 2014