A Trial to Evaluate Immunogenicity and Safety of Three Consecutive Production Lots of IMVAMUNE® (MVA-BN®) Smallpox Vaccine in Healthy, Vaccinia-naïve Subjects

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bavarian Nordic
ClinicalTrials.gov Identifier:
NCT01144637
First received: June 14, 2010
Last updated: November 19, 2013
Last verified: November 2013
  Purpose

A randomized, double-blind, placebo-controlled Phase III trial to evaluate immunogenicity and safety of three consecutive production lots of IMVAMUNE® (MVA-BN®) smallpox vaccine in healthy, vaccinia-naïve subjects.


Condition Intervention Phase
Smallpox
Biological: IMVAMUNE
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial to Evaluate Immunogenicity and Safety of Three Consecutive Production Lots of IMVAMUNE® (MVA-BN®) Smallpox Vaccine in Healthy, Vaccinia-Naïve Subjects

Resource links provided by NLM:


Further study details as provided by Bavarian Nordic:

Primary Outcome Measures:
  • Geometric Mean Titers (GMTs) measured by PRNT [ Time Frame: Visit 4 (Day 42) ] [ Designated as safety issue: No ]
    Geometric Mean Titers (GMTs) after two IMVAMUNE® vaccinations measured by Plaque Reduction Neutralization Test (PRNT) at trial Visit 4.


Secondary Outcome Measures:
  • GMT measured by ELISA [ Time Frame: Visit 4 (Day 42) ] [ Designated as safety issue: No ]
    GMTs after two IMVAMUNE® vaccinations measured by Enzyme-linked Immunosorbent Assay (ELISA) at trial Visit 4

  • Seroconversion [ Time Frame: Visit 4 (Day 42) ] [ Designated as safety issue: No ]
    PRNT and ELISA seroconversion rates at trial Visit 4

  • Pearson Correlation Coefficient [ Time Frame: Visit 4 (Day 42) ] [ Designated as safety issue: No ]
    Pearson Correlation Coefficient between the log10 transformed PRNT titers and the log10 transformed ELISA titers at trial Visit 4

  • Serious Adverse Events [ Time Frame: Any Time ] [ Designated as safety issue: Yes ]
    Occurrence, relationship and intensity of any Serious Adverse Event (SAE) at any time during the trial

  • Cardiac sign or symptom [ Time Frame: Any time ] [ Designated as safety issue: Yes ]
    Occurrence, relationship and intensity of any cardiac sign or symptom indicating a case of myo-/pericarditis

  • 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 vaccine within 28 days after vaccination

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

  • Solicited local AEs [ 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, 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


Estimated Enrollment: 4000
Study Start Date: February 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose) (Lot 1)
Biological: IMVAMUNE
Experimental: Group 2
Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose) (Lot 2)
Biological: IMVAMUNE
Experimental: Group 3
Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose) (Lot 3)
Biological: IMVAMUNE
Placebo Comparator: Group 4
Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml placebo (Tris-buffered saline, TBS)
Other: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male and female subjects, 18 to 40 years of age
  • The subject has read, signed and dated the 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
  • 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 and a negative urine pregnancy test within 24 hours prior to each vaccination
  • White blood cells ≥ 2,500/mm3 < 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:

    • a. Total bilirubin ≤ 1.5 x ULN in the absence of other evidence of significant liver disease
    • b. 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 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 prior to 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
  • History of or active autoimmune disease, persons with vitiligo or thyroid disease taking thyroid replacement are not excluded
  • Known or suspected impairment of immunologic function including, but not limited to, HIV Infection, clinically significant liver disease (including chronic active HBV or HCV), 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 pectoris, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, or any other heart condition under the care of a doctor
  • Known history of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before age 50 years
  • 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 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 know allergy to egg or aminoglycosides
  • History of anaphylaxis or severe allergic reaction to any vaccine
  • Acute disease (illness with or without a fever) at the time 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 to or after trial vaccination
  • Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior to 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 (V5)
  • 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 (V5)
  • 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
  • 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: NCT01144637

  Show 34 Study Locations
Sponsors and Collaborators
Bavarian Nordic
Investigators
Principal Investigator: Turner Overton, MD Division of Infectious Diseases University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: Bavarian Nordic
ClinicalTrials.gov Identifier: NCT01144637     History of Changes
Other Study ID Numbers: POX-MVA-013
Study First Received: June 14, 2010
Last Updated: November 19, 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 August 21, 2014