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A Randomized, Double-blind, Placebo-controlled Study on Immunogenicity and Safety of MVA-BN (IMVAMUNE™) Smallpox Vaccine in Healthy Subjects

Primary Purpose

Smallpox

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
MVA-BN® (IMVAMUNE)
Placebo
Sponsored by
Bavarian Nordic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Smallpox focused on measuring Smallpox, Vaccination, Prevention

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Male and female subjects between 18 and 55 years of age. Women must have a negative serum pregnancy test at screening and a negative urine or serum pregnancy test within 24 hours prior to vaccination. Women of childbearing potential 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 study, and must not become pregnant for at least 28 days after the last vaccination. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products.) Lab values without clinically significant findings Electrocardiogram (ECG) without abnormal 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, 2 premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia). Groups 1, 2 and 3 (All vaccinia-naïve subjects) additionally: No history of known or suspected previous smallpox vaccination. No detectable vaccinia scar. Group 4 (All previously vaccinated subjects) additionally: History of previous smallpox vaccination (documented and/or typical vaccinia scar). Most recent smallpox vaccination ≥ 5 years. Exclusion Criteria: Uncontrolled serious infection i.e. not responding to antimicrobial therapy. 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, clinically significant liver disease; 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 at the vaccination site are excluded. 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. History of an immediate family member (father, mother, brother, or sister) who died due to 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 volunteers 20 years of age and older. History of anaphylaxis or severe allergic reaction. Immune modulatory therapy. History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject. History or clinical manifestation of clinically significant and severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders.

Sites / Locations

  • Harrison Clinical Research GmbH

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Placebo Comparator

Experimental

Arm Label

GP 1: two x 1x10E08 TCID, MVA-BN® s.c., vaccinia naive

GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., vaccinia naive

GP 3: two x Placebo, s.c., vaccinia naive

GP 4: 1x10E08 TCID, MVA-BN®, s.c., vaccinia experienced

Arm Description

vaccinia naive subjects receiving two subcutanenous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)

vaccinica naive subjects receiving one vaccination with 0.5ml MVA-BN® IMVAMUNE(1x10E08 TCID), followed by one vaccination Placebo (0.5ml Tris Buffer)

vaccinia naive subjects, receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer).

vaccinia experienced subjects, receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID).

Outcomes

Primary Outcome Measures

Percentage of Participants With Seroconversion by ELISA
Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Number of Participants With ECG Changes
Occurrence of any specific or unspecific ECG change. Assessments at Screening (SCR), Visit 2 (Week 2) and Visit 4 (Week 6).
Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])
Occurrence and relationship of any other cardiac symptom at any time during the study

Secondary Outcome Measures

Percentage of Participants With Seroconversion by ELISA
Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Percentage of Participants With Seroconversion by PRNT
Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (6) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Percentage of Participants With Seroconversion by PRNT
Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (6) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Number of Participants With Related Serious Adverse Events
Number of participants with any serious adverse event possibly, probably or definitely related to the study vaccine at any time during the study
Number of Participants With Solicited Local Adverse Events
Number of participants with solicited local AEs (pain, erythema, swelling and induration) within 8 days after any vaccination (vaccinations for Groups 1-3: Days 0 and 28; Group 4: Day 0). Percentages based on subjects with at least one completed diary card.
Number of Participants With Solicited General Adverse Events
Number of participants with solicited systemic/general AEs (body temperature increased, headache, myalgia, nausea, and fatigue) within 8 days after any vaccination (vaccinations for Groups 1-3: Days 0 and 28; Group 4: Day 0). Percentages based on subjects with at least one completed diary card.
Number of Participants With Related Grade>=3 Adverse Events
Number of participants with any Grade >=3 AE probably, possibly, or definitely related to the study vaccine within 4 weeks after any vaccination (vaccinations for Groups 1-3: Days 0 and 28; Group 4: Day 0). Pooled solicited (local and general) and unsolicited AEs.
Number of Participants With Unsolicited Non-serious Adverse Events
Number of participants with non-serious unsolicited AEs within 4 weeks after any vaccination (vaccinations for Groups 1-3: Days 0 and 28; Group 4: Day 0).

Full Information

First Posted
April 19, 2006
Last Updated
February 11, 2019
Sponsor
Bavarian Nordic
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00316524
Brief Title
A Randomized, Double-blind, Placebo-controlled Study on Immunogenicity and Safety of MVA-BN (IMVAMUNE™) Smallpox Vaccine in Healthy Subjects
Official Title
A Partially Randomized, Partially Double-blind, Placebo-controlled Phase II Non-inferiority Study to Evaluate Immunogenicity and Safety of One and Two Doses of MVA-BN® (IMVAMUNE™) Smallpox Vaccine in 18-55 Year Old Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
April 2006 (Actual)
Primary Completion Date
February 2007 (Actual)
Study Completion Date
August 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bavarian Nordic
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
The primary objective of this study is to evaluate the immune response after a single vaccination of pre-immune subjects compared to two vaccinations in naive subjects. In addition the study further investigates the cardiac safety profile of MVA-BN® in a healthy population compared to placebo.
Detailed Description
The study consists of 4 groups, which receive either MVA-BN once, MVA-BN two times, MVA-BN followed by placebo, or two administrations of placebo.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Smallpox
Keywords
Smallpox, Vaccination, Prevention

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
745 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GP 1: two x 1x10E08 TCID, MVA-BN® s.c., vaccinia naive
Arm Type
Experimental
Arm Description
vaccinia naive subjects receiving two subcutanenous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
Arm Title
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., vaccinia naive
Arm Type
Experimental
Arm Description
vaccinica naive subjects receiving one vaccination with 0.5ml MVA-BN® IMVAMUNE(1x10E08 TCID), followed by one vaccination Placebo (0.5ml Tris Buffer)
Arm Title
GP 3: two x Placebo, s.c., vaccinia naive
Arm Type
Placebo Comparator
Arm Description
vaccinia naive subjects, receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer).
Arm Title
GP 4: 1x10E08 TCID, MVA-BN®, s.c., vaccinia experienced
Arm Type
Experimental
Arm Description
vaccinia experienced subjects, receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID).
Intervention Type
Biological
Intervention Name(s)
MVA-BN® (IMVAMUNE)
Intervention Description
1x 10E8_TCID50
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Tris-Buffer
Primary Outcome Measure Information:
Title
Percentage of Participants With Seroconversion by ELISA
Description
Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Time Frame
2 weeks following the last vaccination (Week 6 for Groups 1-3, Week 2 for Group 4)
Title
Number of Participants With ECG Changes
Description
Occurrence of any specific or unspecific ECG change. Assessments at Screening (SCR), Visit 2 (Week 2) and Visit 4 (Week 6).
Time Frame
within 2 weeks after each vaccination
Title
Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])
Description
Occurrence and relationship of any other cardiac symptom at any time during the study
Time Frame
within 32 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With Seroconversion by ELISA
Description
Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Time Frame
4 weeks following the last vaccination (Week 8 for Groups 1-3, Week 4 for Group 4)
Title
Percentage of Participants With Seroconversion by PRNT
Description
Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (6) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Time Frame
2 weeks following the last vaccination (Week 6 for Groups 1-3, Week 2 for Group 4)
Title
Percentage of Participants With Seroconversion by PRNT
Description
Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (6) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Time Frame
4 weeks following the last vaccination (Week 8 for Groups 1-3, Week 4 for Group 4)
Title
Number of Participants With Related Serious Adverse Events
Description
Number of participants with any serious adverse event possibly, probably or definitely related to the study vaccine at any time during the study
Time Frame
within 32 weeks
Title
Number of Participants With Solicited Local Adverse Events
Description
Number of participants with solicited local AEs (pain, erythema, swelling and induration) within 8 days after any vaccination (vaccinations for Groups 1-3: Days 0 and 28; Group 4: Day 0). Percentages based on subjects with at least one completed diary card.
Time Frame
within 8 days after any vaccination
Title
Number of Participants With Solicited General Adverse Events
Description
Number of participants with solicited systemic/general AEs (body temperature increased, headache, myalgia, nausea, and fatigue) within 8 days after any vaccination (vaccinations for Groups 1-3: Days 0 and 28; Group 4: Day 0). Percentages based on subjects with at least one completed diary card.
Time Frame
within 8 days after any vaccination
Title
Number of Participants With Related Grade>=3 Adverse Events
Description
Number of participants with any Grade >=3 AE probably, possibly, or definitely related to the study vaccine within 4 weeks after any vaccination (vaccinations for Groups 1-3: Days 0 and 28; Group 4: Day 0). Pooled solicited (local and general) and unsolicited AEs.
Time Frame
within 4 weeks after any vaccination
Title
Number of Participants With Unsolicited Non-serious Adverse Events
Description
Number of participants with non-serious unsolicited AEs within 4 weeks after any vaccination (vaccinations for Groups 1-3: Days 0 and 28; Group 4: Day 0).
Time Frame
within 4 weeks after any vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male and female subjects between 18 and 55 years of age. Women must have a negative serum pregnancy test at screening and a negative urine or serum pregnancy test within 24 hours prior to vaccination. Women of childbearing potential 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 study, and must not become pregnant for at least 28 days after the last vaccination. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products.) Lab values without clinically significant findings Electrocardiogram (ECG) without abnormal 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, 2 premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia). Groups 1, 2 and 3 (All vaccinia-naïve subjects) additionally: No history of known or suspected previous smallpox vaccination. No detectable vaccinia scar. Group 4 (All previously vaccinated subjects) additionally: History of previous smallpox vaccination (documented and/or typical vaccinia scar). Most recent smallpox vaccination ≥ 5 years. Exclusion Criteria: Uncontrolled serious infection i.e. not responding to antimicrobial therapy. 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, clinically significant liver disease; 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 at the vaccination site are excluded. 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. History of an immediate family member (father, mother, brother, or sister) who died due to 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 volunteers 20 years of age and older. History of anaphylaxis or severe allergic reaction. Immune modulatory therapy. History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject. History or clinical manifestation of clinically significant and severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank von Sonnenburg, Prof
Organizational Affiliation
Section of International Medicine & Public Health, Department of Infectious Diseases and Tropical Medicine, Ludwig-Maximilians Unviersity Munich
Official's Role
Principal Investigator
Facility Information:
Facility Name
Harrison Clinical Research GmbH
City
Munich
State/Province
Bavaria
ZIP/Postal Code
80636
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
25879867
Citation
Zitzmann-Roth EM, von Sonnenburg F, de la Motte S, Arndtz-Wiedemann N, von Krempelhuber A, Uebler N, Vollmar J, Virgin G, Chaplin P. Cardiac safety of Modified Vaccinia Ankara for vaccination against smallpox in a young, healthy study population. PLoS One. 2015 Apr 16;10(4):e0122653. doi: 10.1371/journal.pone.0122653. eCollection 2015.
Results Reference
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A Randomized, Double-blind, Placebo-controlled Study on Immunogenicity and Safety of MVA-BN (IMVAMUNE™) Smallpox Vaccine in Healthy Subjects

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