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

NCT ID: NCT01144637

Last Updated: 2019-01-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 4005 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2014-06-30

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.

Conditions

Smallpox

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1

Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1

Group Type: EXPERIMENTAL

IMVAMUNE®

Intervention Type: BIOLOGICAL

0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)

Group 2

Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2

Group Type: EXPERIMENTAL

IMVAMUNE®

Intervention Type: BIOLOGICAL

0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)

Group 3

Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3

Group Type: EXPERIMENTAL

IMVAMUNE®

Intervention Type: BIOLOGICAL

0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)

Group 4

Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

0.5 ml TBS

Interventions

IMVAMUNE®

0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)

Intervention Type: BIOLOGICAL

Placebo

0.5 ml TBS

Intervention Type: OTHER

Other Intervention Names

IMVANEX; MVA-BN®; Tris-buffered-saline

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Bavarian Nordic

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Turner Overton, MD

Role: PRINCIPAL_INVESTIGATOR

Division of Infectious Diseases University of Alabama at Birmingham

Locations

Alabama Vaccine Research Clinic

Birmingham, Alabama, United States

Anaheim Clinical Trials

Anaheim, California, United States

National Research Institute

Los Angeles, California, United States

Northern California Clinical Research Center (NCCRC)

Redding, California, United States

Therapeutics Clinical Research

San Diego, California, United States

Lynn Institute of the Rockies

Colorado Springs, Colorado, United States

Avail Clinical Research, LLC

DeLand, Florida, United States

Broward Research Group

Hollywood, Florida, United States

Accelovance Melbourne

Melbourne, Florida, United States

Southeast Regional Research Group

Savannah, Georgia, United States

Advanced Clinical Research, Inc.

Meridian, Idaho, United States

Accelovance Peoria

Peoria, Illinois, United States

Heartland Research Associates

Augusta, Kansas, United States

Heartland Research Associates, LLC

Wichita, Kansas, United States

Benchmark Research

Metairie, Louisiana, United States

QPS Bio-Kinetic

Springfield, Missouri, United States

Washington University in St. Louis, School of Medicine

St Louis, Missouri, United States

Meridian Clinical Research, LLC

Omaha, Nebraska, United States

Clinical Research Center of Nevada, LLC

Las Vegas, Nevada, United States

Rochester Clinical Research, Inc.

Rochester, New York, United States

Wake Research Associates

Raleigh, North Carolina, United States

Rapid Medical Research, Inc.

Cleveland, Ohio, United States

Family Practice Center of Wooster

Wooster, Ohio, United States

Lynn Health Science Institute

Oklahoma City, Oklahoma, United States

Columbia Research Group, Inc.

Portland, Oregon, United States

Omega Medical Research

Warwick, Rhode Island, United States

PMG Research of Charleston

Mt. Pleasant, South Carolina, United States

Holston Medical Group

Bristol, Tennessee, United States

Volunteer Research Group

Knoxville, Tennessee, United States

Benchmark Research

Fort Worth, Texas, United States

Tanner Clinic

Layton, Utah, United States

Advanced Clinical Research

West Jordan, Utah, United States

Clinical Research Associates of Tidewater

Norfolk, Virginia, United States

University Physicians Internal Medicine University Physicians & Surgeons, Inc.

Huntington, West Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29652929 (View on PubMed)

Other Identifiers

POX-MVA-013

Identifier Type: -

Identifier Source: org_study_id