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

NCT01144637 | Completed Phase 3 Results DMC

• 1 other identifier: POX-MVA-013
• Study Type: interventional
• Target: 4,005
• Locations: 1 country
• Sites: 34

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

Outcome Measures

Primary Outcomes (1)

• PRNT GMT

  Geometric Mean Titers (GMT) based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Titers below the detection limit are included with a value of '1'.

  2 weeks following the second vaccination

Secondary Outcomes (11)

• ELISA GMT

  2 weeks following the second vaccination

• PRNT Seroconversion Rate

  2 weeks following the second vaccination

• ELISA Seroconversion Rate

  2 weeks following the second vaccination

• Correlation PRNT vs ELISA Titers

  2 weeks following the second vaccination

• Serious Adverse Events

  within 30 weeks

Study Arms (4)

Group 1

EXPERIMENTAL

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

Biological: IMVAMUNE®

Group 2

EXPERIMENTAL

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

Biological: IMVAMUNE®

Group 3

EXPERIMENTAL

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

Biological: IMVAMUNE®

Group 4

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

IMVAMUNE® BIOLOGICAL

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

Also known as: IMVANEX, MVA-BN®

Group 1; Group 2; Group 3

Placebo OTHER

0.5 ml TBS

Also known as: Tris-buffered-saline

Group 4

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bavarian Nordic: lead

Study Sites (34)

Alabama Vaccine Research Clinic

Birmingham, Alabama, 35294, United States

Location

Anaheim Clinical Trials

Anaheim, California, 92801, United States

Location

National Research Institute

Los Angeles, California, 90057, United States

Location

Northern California Clinical Research Center (NCCRC)

Redding, California, 96001, United States

Location

Therapeutics Clinical Research

San Diego, California, 92123, United States

Location

Lynn Institute of the Rockies

Colorado Springs, Colorado, 80907, United States

Location

Avail Clinical Research, LLC

DeLand, Florida, 32720, United States

Location

Broward Research Group

Hollywood, Florida, 33024, United States

Location

Accelovance Melbourne

Melbourne, Florida, 32935, United States

Location

Southeast Regional Research Group

Savannah, Georgia, 31405, United States

Location

Advanced Clinical Research, Inc.

Meridian, Idaho, 83642, United States

Location

Accelovance Peoria

Peoria, Illinois, 61602, United States

Location

Heartland Research Associates

Augusta, Kansas, 67010, United States

Location

Heartland Research Associates, LLC

Wichita, Kansas, 67207, United States

Location

Benchmark Research

Metairie, Louisiana, 70006, United States

Location

QPS Bio-Kinetic

Springfield, Missouri, 65802, United States

Location

Washington University in St. Louis, School of Medicine

St Louis, Missouri, 63110, United States

Location

Meridian Clinical Research, LLC

Omaha, Nebraska, 68134, United States

Location

Clinical Research Center of Nevada, LLC

Las Vegas, Nevada, 89104, United States

Location

Rochester Clinical Research, Inc.

Rochester, New York, 14609, United States

Location

Wake Research Associates

Raleigh, North Carolina, 27612, United States

Location

Rapid Medical Research, Inc.

Cleveland, Ohio, 44122, United States

Location

Family Practice Center of Wooster

Wooster, Ohio, 44691, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Columbia Research Group, Inc.

Portland, Oregon, 97239, United States

Location

Omega Medical Research

Warwick, Rhode Island, 02886, United States

Location

PMG Research of Charleston

Mt. Pleasant, South Carolina, 29464, United States

Location

Holston Medical Group

Bristol, Tennessee, 37620, United States

Location

Volunteer Research Group

Knoxville, Tennessee, 37920, United States

Location

Benchmark Research

Fort Worth, Texas, 76135, United States

Location

Tanner Clinic

Layton, Utah, 84041, United States

Location

Advanced Clinical Research

West Jordan, Utah, 84088, United States

Location

Clinical Research Associates of Tidewater

Norfolk, Virginia, 23507, United States

Location

University Physicians Internal Medicine University Physicians & Surgeons, Inc.

Huntington, West Virginia, 25701, United States

Location

Related Publications (1)

• 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.

  PMID: 29652929 DERIVED

MeSH Terms

Conditions

Smallpox

Interventions

smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Program Lead, Clinical Operations
• Organization: Bavarian Nordic A/S

info@bavarian-nordic.com

+45 3326

Study Officials

• Turner Overton, MD

  Division of Infectious Diseases University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2010
• First Posted: June 15, 2010
• Study Start: February 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: June 1, 2014
• Last Updated: January 3, 2019
• Results First Posted: January 3, 2019

Record last verified: 2018-12

Locations

US (34)