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An Open-Label Phase II Study to Evaluate Immunogenicity and Safety of a Single IMVAMUNE Booster Vaccination Two Years After the Last IMVAMUNE Vaccination in Former POX-MVA-005 Vaccinees

Primary Purpose

Smallpox

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
IMVAMUNE
IMVAMUNE
Blood Draw Only
Sponsored by
Bavarian Nordic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Smallpox

Eligibility Criteria

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

Inclusion Criteria:

Groups 1 and 2 (first consenting 75 subjects in each group to be vaccinated)

  • Male and female subjects having participated in Group 1 or 2 of the study POX-MVA-005 who completed the trial according to protocol.
  • Women of childbearing potential 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 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 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.)
  • Read, signed and dated informed consent document after being advised of the risks and benefits of the study in a language understood by the subject signed, and prior to performance of any study specific procedure.
  • Troponin I within normal institutional limits.
  • White blood cells ≥ 2,500/mm3 and <= 11,000/mm3.
  • Absolute neutrophil count within normal limits.
  • Negative urine glucose by dipstick or urinalysis.
  • Hemoglobin within the laboratory reference ranges (unless the investigator considers the deviation to be not clinically significant).
  • Platelets 100 - 440/nL.
  • Adequate renal function defined as:

    1. Serum creatinine without clinically significant findings.
    2. Urine protein <= 30 mg/dL or none or trace proteinuria (by urinalysis or dip stick).
  • Adequate hepatic function defined as:

    1. Total bilirubin <= 1.5 x upper limit of normal (ULN) in the absence of other evidence of significant liver disease (healthy subjects without clinical disease; Morbus Meulengracht can be included).
    2. AST (SGOT), ALT (SGPT), alkaline phosphatase without clinically significant findings.
  • Electrocardiogram (ECG) without clinically relevant 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, two premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia).

Group 4 (all subjects) and Groups 1 and 2 (subjects N > 75): blood draw only

  • Male and female subjects having participated in the study POX-MVA-005 who completed the trial according to protocol.
  • Read, signed and dated informed consent document after being advised of the risks and benefits of the blood draw in a language understood by the subject signed, and prior to performance of the blood draw.

Exclusion Criteria:

Groups 1 and 2 (first consenting 75 subjects in each group to be vaccinated)

  • Participation in another study with a smallpox vaccine after the POX-MVA-005 study.
  • 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.
  • 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 must not be vaccinated at the previous site of cancer.
  • History or clinical manifestation of clinically significant and severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders.
  • Clinically significant mental disorder not adequately controlled by medical treatment.
  • Any condition which might interfere with study objectives or would limit the subject's ability to complete the study or to be compliant in the opinion of the investigator.
  • 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.
  • Twenty 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).
  • History of intravenous drug abuse.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. tris (hydroxymethyl)-amino methane, chicken embryo fibroblast proteins, aminoglycosides (gentamycin).
  • History of any anaphylactic shock or severe allergic reaction requiring immediate treatment.
  • Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior or after study vaccination.
  • Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior or after study vaccination.
  • Chronic administration (defined as more than 14 days) of > 5 mg prednisone (or equivalent) per day or any other immune-modifying drugs during a period starting from three months prior to administration of the vaccine and ending at study conclusion (Visit 4).
  • 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 3 months prior to administration of the vaccine and ending at study conclusion.
  • Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding administration of the study vaccine, or planned administration of such a drug during the study period.

Group 4 (all subjects) and Groups 1 and 2 (subjects N > 75): blood draw only

  • Participation in another study with a smallpox vaccine after the POX-MVA-005 study.
  • Any condition which might interfere with a blood draw.

Sites / Locations

  • Harrison Clinical Research Deutschland GmbH

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Other

Arm Label

Initially Vaccinia Naive, 2 dose primed, 1 booster dose

Initially Vaccinia Naive, 1 dose primed, 1 booster dose

Vaccinia Experienced, boosted, blood draw only

Arm Description

Group 1 Initially Vaccinia Naive Subjects 2 doses of MVA-BN in prior study (POX-MVA-005) 1 booster dose of MVA-BN (POX-MVA-023) IMVAMUNE: 1x 10E8_TCID50

Group 2 Initially Vaccinia Naive Subjects 1 dose of MVA-BN and 1x Placebo in prior study (POX-MVA-005) 1 booster dose of MVA-BN (POX-MVA-023) IMVAMUNE: 1x 10E8_TCID50

Group 4 Vaccinia Experienced 1 booster dose of MVA-BN in prior study (POX-MVA-005) Blood draw, Screening Visit only (POX-MVA-023)

Outcomes

Primary Outcome Measures

Individual Peak Booster Rate by ELISA (Percentage of Participants)
Booster rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA) is defined as the percentage of subjects with an appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual Peak booster rate is based on the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Percentages based on number of subjects with data available.

Secondary Outcome Measures

Booster Rate by ELISA (Percentage of Participants)
Booster rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA) is defined as the percentage of subjects with an appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
ELISA GMT
Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Individual peak is defined as the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Titers below the detection limit are included with a value of '1'.
Booster Rate by PRNT (Percentage of Participants)
Booster rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT) is defined as the percentage of subjects with an appearance of antibody titers ≥ detection limit (6) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual Peak booster rate is based on the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Percentages based on number of subjects with data available.
PRNT GMT
Geometric Mean Titers (GMT) based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Individual peak is defined as the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Titers below the detection limit are included with a value of '1'.
Correlation PRNT vs ELISA Titers
Pearson Correlation Coefficient between the log10 transformed PRNT titers and the log10 transformed ELISA titers
Number of Participants With Related Serious Adverse Events
Number of participants with Serious Adverse Events (SAEs) probably, possibly or definitely related to the trial vaccine
Number of Participants With Unsolicited Non-serious Adverse Events
Number of participants with any, grade >=3, and related non-serious unsolicited adverse events
Number of Participants With Related Grade >= 3 Unsolicited Adverse Events
Number of participants with Grade >=3 Unsolicited Adverse Event probably, possibly, or definitely related to the study vaccine
Number of Participants With Solicited Local Adverse Events
Number of participants with and intensity of solicited local AEs (pain, erythema, swelling, induration, and pruritis). Percentages based on subjects with a completed diary card.
Number of Participants With Solicited General Adverse Events
Number of participants with solicited general AEs (body temperature increased, headache, myalgia, nausea, and fatigue): Intensity and relationship to vaccination. Percentages based on subjects with a completed diary card.

Full Information

First Posted
May 27, 2008
Last Updated
February 18, 2019
Sponsor
Bavarian Nordic
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00686582
Brief Title
An Open-Label Phase II Study to Evaluate Immunogenicity and Safety of a Single IMVAMUNE Booster Vaccination Two Years After the Last IMVAMUNE Vaccination in Former POX-MVA-005 Vaccinees
Official Title
An Open-Label Phase II Study to Evaluate Immunogenicity and Safety of a Single IMVAMUNE Booster Vaccination Two Years After the Last IMVAMUNE Vaccination in Former POX-MVA-005 Vaccinees
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
August 2008 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
June 2009 (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

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The study was preformed to evaluate the persistence of antibodies following vaccination with MVA-BN and to assess the immunological memory response induced by a booster vaccination with MVA-BN in subjects two years after their participation in trial POX-MVA-005 (NCT00316524) in which they had received one or two doses of MVA-BN.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
304 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Initially Vaccinia Naive, 2 dose primed, 1 booster dose
Arm Type
Experimental
Arm Description
Group 1 Initially Vaccinia Naive Subjects 2 doses of MVA-BN in prior study (POX-MVA-005) 1 booster dose of MVA-BN (POX-MVA-023) IMVAMUNE: 1x 10E8_TCID50
Arm Title
Initially Vaccinia Naive, 1 dose primed, 1 booster dose
Arm Type
Experimental
Arm Description
Group 2 Initially Vaccinia Naive Subjects 1 dose of MVA-BN and 1x Placebo in prior study (POX-MVA-005) 1 booster dose of MVA-BN (POX-MVA-023) IMVAMUNE: 1x 10E8_TCID50
Arm Title
Vaccinia Experienced, boosted, blood draw only
Arm Type
Other
Arm Description
Group 4 Vaccinia Experienced 1 booster dose of MVA-BN in prior study (POX-MVA-005) Blood draw, Screening Visit only (POX-MVA-023)
Intervention Type
Biological
Intervention Name(s)
IMVAMUNE
Intervention Description
1x 10E8_TCID50
Intervention Type
Biological
Intervention Name(s)
IMVAMUNE
Intervention Description
1x 10E8_TCID50
Intervention Type
Procedure
Intervention Name(s)
Blood Draw Only
Primary Outcome Measure Information:
Title
Individual Peak Booster Rate by ELISA (Percentage of Participants)
Description
Booster rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA) is defined as the percentage of subjects with an appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual Peak booster rate is based on the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Percentages based on number of subjects with data available.
Time Frame
within 4 weeks
Secondary Outcome Measure Information:
Title
Booster Rate by ELISA (Percentage of Participants)
Description
Booster rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA) is defined as the percentage of subjects with an appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Time Frame
within 26 weeks
Title
ELISA GMT
Description
Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Individual peak is defined as the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Titers below the detection limit are included with a value of '1'.
Time Frame
within 26 weeks
Title
Booster Rate by PRNT (Percentage of Participants)
Description
Booster rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT) is defined as the percentage of subjects with an appearance of antibody titers ≥ detection limit (6) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual Peak booster rate is based on the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Percentages based on number of subjects with data available.
Time Frame
within 26 weeks
Title
PRNT GMT
Description
Geometric Mean Titers (GMT) based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Individual peak is defined as the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Titers below the detection limit are included with a value of '1'.
Time Frame
within 26 weeks
Title
Correlation PRNT vs ELISA Titers
Description
Pearson Correlation Coefficient between the log10 transformed PRNT titers and the log10 transformed ELISA titers
Time Frame
within 26 weeks
Title
Number of Participants With Related Serious Adverse Events
Description
Number of participants with Serious Adverse Events (SAEs) probably, possibly or definitely related to the trial vaccine
Time Frame
within 26 weeks
Title
Number of Participants With Unsolicited Non-serious Adverse Events
Description
Number of participants with any, grade >=3, and related non-serious unsolicited adverse events
Time Frame
within 29 days after any vaccination
Title
Number of Participants With Related Grade >= 3 Unsolicited Adverse Events
Description
Number of participants with Grade >=3 Unsolicited Adverse Event probably, possibly, or definitely related to the study vaccine
Time Frame
within 29 days after vaccination
Title
Number of Participants With Solicited Local Adverse Events
Description
Number of participants with and intensity of solicited local AEs (pain, erythema, swelling, induration, and pruritis). Percentages based on subjects with a completed diary card.
Time Frame
within 8 days after vaccination
Title
Number of Participants With Solicited General Adverse Events
Description
Number of participants with solicited general AEs (body temperature increased, headache, myalgia, nausea, and fatigue): Intensity and relationship to vaccination. Percentages based on subjects with a completed diary card.
Time Frame
within 8 days after 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: Groups 1 and 2 (first consenting 75 subjects in each group to be vaccinated) Male and female subjects having participated in Group 1 or 2 of the study POX-MVA-005 who completed the trial according to protocol. Women of childbearing potential 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 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 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.) Read, signed and dated informed consent document after being advised of the risks and benefits of the study in a language understood by the subject signed, and prior to performance of any study specific procedure. Troponin I within normal institutional limits. White blood cells ≥ 2,500/mm3 and <= 11,000/mm3. Absolute neutrophil count within normal limits. Negative urine glucose by dipstick or urinalysis. Hemoglobin within the laboratory reference ranges (unless the investigator considers the deviation to be not clinically significant). Platelets 100 - 440/nL. Adequate renal function defined as: Serum creatinine without clinically significant findings. Urine protein <= 30 mg/dL or none or trace proteinuria (by urinalysis or dip stick). Adequate hepatic function defined as: Total bilirubin <= 1.5 x upper limit of normal (ULN) in the absence of other evidence of significant liver disease (healthy subjects without clinical disease; Morbus Meulengracht can be included). AST (SGOT), ALT (SGPT), alkaline phosphatase without clinically significant findings. Electrocardiogram (ECG) without clinically relevant 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, two premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia). Group 4 (all subjects) and Groups 1 and 2 (subjects N > 75): blood draw only Male and female subjects having participated in the study POX-MVA-005 who completed the trial according to protocol. Read, signed and dated informed consent document after being advised of the risks and benefits of the blood draw in a language understood by the subject signed, and prior to performance of the blood draw. Exclusion Criteria: Groups 1 and 2 (first consenting 75 subjects in each group to be vaccinated) Participation in another study with a smallpox vaccine after the POX-MVA-005 study. 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. 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 must not be vaccinated at the previous site of cancer. History or clinical manifestation of clinically significant and severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders. Clinically significant mental disorder not adequately controlled by medical treatment. Any condition which might interfere with study objectives or would limit the subject's ability to complete the study or to be compliant in the opinion of the investigator. 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. Twenty 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). History of intravenous drug abuse. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. tris (hydroxymethyl)-amino methane, chicken embryo fibroblast proteins, aminoglycosides (gentamycin). History of any anaphylactic shock or severe allergic reaction requiring immediate treatment. Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior or after study vaccination. Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior or after study vaccination. Chronic administration (defined as more than 14 days) of > 5 mg prednisone (or equivalent) per day or any other immune-modifying drugs during a period starting from three months prior to administration of the vaccine and ending at study conclusion (Visit 4). 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 3 months prior to administration of the vaccine and ending at study conclusion. Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding administration of the study vaccine, or planned administration of such a drug during the study period. Group 4 (all subjects) and Groups 1 and 2 (subjects N > 75): blood draw only Participation in another study with a smallpox vaccine after the POX-MVA-005 study. Any condition which might interfere with a blood draw.
Facility Information:
Facility Name
Harrison Clinical Research Deutschland GmbH
City
München
ZIP/Postal Code
80636
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

An Open-Label Phase II Study to Evaluate Immunogenicity and Safety of a Single IMVAMUNE Booster Vaccination Two Years After the Last IMVAMUNE Vaccination in Former POX-MVA-005 Vaccinees

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