Clinical trial NCT01144637: A Trial to Evaluate Immunogenicity and Safety of Three Consecutive Production Lots of IMVAMUNE® (MVA-BN®) Smallpox Vaccine in Healthy, Vaccinia-naïve Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Smallpox
Lead sponsor: Bavarian Nordic
Sponsor class: INDUSTRY
First posted: 2010-06-15
Enrollment: 4005
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: PRNT GMT
timeFrame: 2 weeks following the second vaccination
Secondary outcomes:
measure: ELISA GMT
timeFrame: 2 weeks following the second vaccination
measure: PRNT Seroconversion Rate
timeFrame: 2 weeks following the second vaccination
measure: ELISA Seroconversion Rate
timeFrame: 2 weeks following the second vaccination
measure: Correlation PRNT vs ELISA Titers
timeFrame: 2 weeks following the second vaccination
measure: Serious Adverse Events
timeFrame: within 30 weeks
measure: Cardiac Signs or Symptoms
timeFrame: within 30 weeks
measure: Related Grade >=3 Adverse Events
timeFrame: within 29 days after any vaccination
measure: Unsolicited Non-serious AEs: Intensity
timeFrame: within 29 days after any vaccination
measure: Unsolicited Non-serious AEs: Relationship to Vaccination
timeFrame: within 29 days after any vaccination
measure: Solicited Local AEs
timeFrame: within 8 days after any vaccination
measure: Solicited General AEs
timeFrame: within 8 days after any vaccination
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Vaccine Research Clinic
state: Alabama
city: Anaheim
country: United States
facility: Anaheim Clinical Trials
state: California
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: Redding
country: United States
facility: Northern California Clinical Research Center (NCCRC)
state: California
city: San Diego
country: United States
facility: Therapeutics Clinical Research
state: California
city: Colorado Springs
country: United States
facility: Lynn Institute of the Rockies
state: Colorado
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Hollywood
country: United States
facility: Broward Research Group
state: Florida
city: Melbourne
country: United States
facility: Accelovance Melbourne
state: Florida
city: Savannah
country: United States
facility: Southeast Regional Research Group
state: Georgia
city: Meridian
country: United States
facility: Advanced Clinical Research, Inc.
state: Idaho
city: Peoria
country: United States
facility: Accelovance Peoria
state: Illinois
city: Augusta
country: United States
facility: Heartland Research Associates
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Metairie
country: United States
facility: Benchmark Research
state: Louisiana
city: Saint Louis
country: United States
facility: Washington University in St. Louis, School of Medicine
state: Missouri
city: Springfield
country: United States
facility: QPS Bio-Kinetic
state: Missouri
city: Omaha
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada, LLC
state: Nevada
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc.
state: New York
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc.
state: Ohio
city: Wooster
country: United States
facility: Family Practice Center of Wooster
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Portland
country: United States
facility: Columbia Research Group, Inc.
state: Oregon
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Mount Pleasant
country: United States
facility: PMG Research of Charleston
state: South Carolina
city: Bristol
country: United States
facility: Holston Medical Group
state: Tennessee
city: Knoxville
country: United States
facility: Volunteer Research Group
state: Tennessee
city: Fort Worth
country: United States
facility: Benchmark Research
state: Texas
city: Layton
country: United States
facility: Tanner Clinic
state: Utah
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater
state: Virginia
city: Huntington
country: United States
facility: University Physicians Internal Medicine University Physicians & Surgeons, Inc.
state: West Virginia
Study officials:
affiliation: Division of Infectious Diseases University of Alabama at Birmingham
name: Turner Overton, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Overton ET, Lawrence SJ, Wagner E, Nopora K, Rosch S, Young P, Schmidt D, Kreusel C, De Carli S, Meyer TP, Weidenthaler H, Samy N, Chaplin P. Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial. PLoS One. 2018 Apr 13;13(4):e0195897. doi: 10.1371/journal.pone.0195897. eCollection 2018.