SmallpoxPhase 2NCT00857493
A Study to Evaluate Safety and Immunogenicity of One and Two Doses of IMVAMUNE® Smallpox Vaccine in 56-80 Year Old Vaccinia-experienced Subjects
A Phase 2 study testing IMVAMUNE in people with Smallpox, run by Bavarian Nordic at 4 sites in United States.
Trial summary
A Randomized, Double-Blind, Placebo-Controlled Phase II Study to Evaluate Safety and Immunogenicity of One and Two Doses of IMVAMUNE® Smallpox Vaccine in 56-80 Year Old Vaccinia-Experienced Subjects Read more about this study
- Who is it for?
- Ages 56 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Smallpox
- What is being tested?
- IMVAMUNE
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 4 sitesUnited States
- Study dates
- Jun 2009to Aug 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 56 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and female subjects 56-70 years of age. If no safety concerns are identified upon review of the safety data from the first 30 subjects enrolled, the age range is extended up to 80 years.
- Time since most current smallpox vaccination > 10 years.
- The subject has read, signed and dated the Informed Consent Form (ICF), successfully completed (at least 90% correct [no more than 3 attempts allowed]) the test of understanding and has signed the Health Insurance Portability and Accountability Act (HIPAA) authorization form.
- Women must have a negative serum pregnancy test at screening and negative urine pregnancy test within 24 hours prior to vaccination.
- 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 study and must not plan to become pregnant for at least 28 days after the last vaccination. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products).
- Weight: ≥ 100 pounds (45.5 kg) and ≤ 330 pounds (150 kg).
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- White blood cells ≥ 2500/mm3 and < 11,000/mm3.
- Absolute neutrophil count within normal limits.
- Hemoglobin within normal limits.
- Platelets within normal limits.
- Adequate renal function defined as:
- Urine protein ≤ +1 (by dip stick)
- Serum creatinine within normal limits
- 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.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 1.5 x ULN.
- Cardiac 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, sustained atrial arrhythmias, sustained ventricular arrhythmia, 2 premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia.
Who cannot join
- History of or active immunodeficiency or immuno-suppression caused by acquired or congenital diseases or caused by treatments such as chronic administration (> 14 days) of systemic, i.e. parenteral or oral, corticosteroids (> 5 mg prednisone [or equivalent] per day), radiation or immune-modifying drugs.
- Periodic steroid injections, e.g. intraarticular, are not allowed within 30 days prior to the first vaccination and throughout the study until Visit 5 (V5).
- Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy.
- 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 prevent the subject from complying with study requirements.
- History of or active autoimmune disease, e.g. Type I diabetes. Persons with vitiligo or thyroid disease taking thyroid hormone replacement are not excluded.
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- Skin cancer in the past six months. If treatment for skin cancer was successfully completed more than six months ago and the malignancy is considered to be cured, the subject may be enrolled. Subjects with history of skin cancer must not be vaccinated at the previous site of cancer.
- Any other malignancy in the past five years. If treatment for cancer was successfully completed more than 5 years ago and the malignancy is considered to be cured, the subject may be enrolled.
- Clinically significant hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders which are not adequately controlled by medical treatment within the last 12 weeks before vaccination as judged by the site's Principal Investigator.
- History of myocardial infarction, congestive heart failure with marked limitation of activity due to symptoms, e.g. walking short distances [20 100 m] (i.e. > Grade II according to the New York Heart Association), cardiomyopathy and stroke or transient ischemic attack in the past two years.
- Uncontrolled high blood pressure defined as systolic blood pressure ≥ 150 mm Hg and/or ≥ diastolic blood pressure ≥ 100 mm Hg within the last six months.
- Subjects with active coronary heart disease manifested by angina, even if on medication.
- 25 % 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
- Clinically significant mental disorder not adequately controlled by medical treatment.
- History of chronic alcohol abuse (40 g/day, e.g. 3 glasses of beer or 2 glasses of wine for at least six months) and/or intravenous drug abuse (within the last six months). Subjects with a history of other substance and/or alcohol abuse are also excluded if - in the opinion of the investigator - the abuse could prevent the subject from complying with study requirements.
- History of allergic disease or reactions likely to be exacerbated by IMVAMUNE® or any component of the vaccine, e.g. tris(hydroxymethyl)-amino methane, chicken embryo fibroblast proteins, aminoglycosides (gentamycin).
- History of anaphylactic shock or any severe allergic reaction to a vaccine requiring immediate treatment.
- Subjects undergoing treatment for tuberculosis infection or disease.
- Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior to or after study vaccination.
- Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior to or after study vaccination.
- Administration or planned administration of immuno-globulins and/or any blood products during a period starting from three 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 the first dose of the study vaccine or planned administration of such a drug during the study period.
- Temperature ≥ 100.4°F (38.0°C) at the time of enrollment.
- Any condition which might interfere with study objectives or would limit the subject's ability to complete the study in the opinion of the investigator.
- Study personnel.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Iowa
Iowa City, Iowa, 52242
University of Kentucky, School of Medicine, Department of Medicine
Lexington, Kentucky, 40536-0084
Orlando Clinical Research Center
Orlando, Florida, 32809
University of Rochester, Medical Center
Rochester, New York, 16462
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Phase II Study to Evaluate Safety and Immunogenicity of One and Two Doses of IMVAMUNE® Smallpox Vaccine in 56-80 Year Old Vaccinia-experienced Subjects
A Randomized, Double-Blind, Placebo-Controlled Phase II Study to Evaluate Safety and Immunogenicity of One and Two Doses of IMVAMUNE® Smallpox Vaccine in 56-80 Year Old Vaccinia-Experienced Subjects
- Conditions
- Smallpox
- Being tested
- IMVAMUNE
- Medical subject headings
- Smallpox
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMVAMUNEBiological
Two s.c. vaccinations with 0.5 ml IMVAMUNE® vaccine containing 1 x 10E8 TCID50 / dose
IMVAMUNEBiological
One s.c. vaccination with placebo (0.5 ml saline), followed by a second s.c. vaccination with 0.5 ml IMVAMUNE® vaccine containing 1 x 10E8 TCID50
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Not described Receives: Biological: IMVAMUNE |
| Group 2 | Experimental | Not described Receives: Biological: IMVAMUNE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Related Serious Adverse Events
Incidence of Serious Adverse Events (SAEs) probably, possibly or definitely related to the trial vaccine
Measured: within 8 weeks
Secondary outcomes (13)
Unsolicited Non-serious AEs: Intensity
Occurrence of unsolicited non-serious AEs by Intensity
Measured: within 29 days after any vaccination
Unsolicited Non-serious AEs: Relationship to Vaccination
Occurrence of unsolicited non-serious AEs by relationship to study vaccine
Measured: within 29 days after any vaccination
Related Grade >=3 Adverse Events
Incidence of any Grade >=3 Adverse Events probably, possibly or definitely related to the trial vaccine. Pooled solicited (general) and unsolicited AEs
Measured: within 29 days after any vaccination
Cardiac Signs or Symptoms
Incidence, relationship and intensity of any cardiac sign or symptom indicating a case of myo-/pericarditis (AESI). AESIs were defined as any cardiac symptoms and ECG changes determined to be clinically significant or cardiac enzymes elevated above 2 x upper limit of normal range (ULN).
Measured: within 32 weeks
Solicited Local Adverse Events
Incidence and intensity of solicited local AEs (pain, erythema, swelling, induration, and pruritus). Percentages based on subjects with at least one completed diary card.
Measured: within 8 days after any vaccination
Solicited General Adverse Events
Incidence of solicited general AEs (body temperature increased, headache, myalgia, chills, nausea, and fatigue): Intensity and relationship tovaccination. Percentages based on subjects with at least one completed diary card.
Measured: within 8 days after any vaccination
ELISA Response Rate
Response rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Response is defined as the 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 response rate is based on the maximum post-Baseline antibody titer within 8 weeks (end of active trial phase). Percentages based on number of subjects with data available.
Measured: within 32 weeks
ELISA Seroconversion Rate
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. Individual peak seroconversion rate is based on the maximum post-Baseline antibody titer within 8 weeks (end of active trial phase). Percentages based on number of subjects with data available.
Measured: within 32 weeks
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 8 weeks (end of active trial phase). Titers below the detection limit are included with a value of '1'.
Measured: within 32 weeks
PRNT Response Rate
Response rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Response is defined as the appearance of antibody titers ≥ detection limit (15) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual peak response rate is based on the maximum post-Baseline antibody titer within 8 weeks (end of active trial phase). Percentages based on number of subjects with data available.
Measured: within 32 weeks
PRNT Seroconversion Rate
Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (15) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual peak seroconversion rate is based on the maximum post-Baseline antibody titer within 8 weeks (end of active trial phase). Percentages based on number of subjects with data available.
Measured: within 32 weeks
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 8 weeks (end of active trial phase). Titers below the detection limit are included with a value of '1'.
Measured: within 32 weeks
Correlation PRNT vs ELISA Titers
Pearson Correlation Coefficient between the log10 transformed PRNT titers and the log10 transformed ELISA titers
Measured: within 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2009 (estimated)
- Study startJun 2009
- Primary completionAug 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SmallpoxStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bavarian Nordic
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Richard N Greenberg, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00857493
- Sponsor's protocol ID
- POX-MVA-024
- Status last verified
- Jan 2019
- First submitted
- 5 Mar 2009
- Last updated
- 10 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Greenberg RN, Hay CM, Stapleton JT, Marbury TC, Wagner E, Kreitmeir E, Roesch S, von Krempelhuber A, Young P, Nichols R, Meyer TP, Schmidt D, Weigl J, Virgin G, Arndtz-Wiedemann N, Chaplin P. A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN(R)) in 56-80-Year-Old Subjects. PLoS One. 2016 Jun 21;11(6):e0157335. doi: 10.1371/journal.pone.0157335. eCollection 2016.
PubMed 27327616
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Phase II Study to Evaluate Safety and Immunogenicity of One and Two Doses of IMVAMUNE® Smallpox Vaccine in 56-80 Year Old Vaccinia-experienced Subjects
- ClinicalTrials.gov ID
- NCT00857493
- Acronym / sponsor ID
- POX-MVA-024
- Conditions
- Smallpox
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Bavarian NordicIndustry (pharma, biotech, devices)
- Study start
- Jun 2009
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 6 Mar 2009 (estimated)
- Results
- Posted 10 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Randomized, Double-Blind, Placebo-Controlled Phase II Study to Evaluate Safety and Immunogenicity of One and Two Doses of IMVAMUNE® Smallpox Vaccine in 56-80 Year Old Vaccinia-Experienced Subjects
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Biological: IMVAMUNE |
| Group 2 | Experimental | Biological: IMVAMUNE |
Who may qualify
- Ages
- 56 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Male and female subjects 56-70 years of age. If no safety concerns are identified upon review of the safety data from the first 30 subjects enrolled, the age range is extended up to 80 years.
- Time since most current smallpox vaccination > 10 years.
- The subject has read, signed and dated the Informed Consent Form (ICF), successfully completed (at least 90% correct [no more than 3 attempts allowed]) the test of understanding and has signed the Health Insurance Portability and Accountability Act (HIPAA) authorization form.
- Women must have a negative serum pregnancy test at screening and negative urine pregnancy test within 24 hours prior to vaccination.
- 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 study and must not plan to become pregnant for at least 28 days after the last vaccination. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products).
Key exclusion criteria (25 listed)
- History of or active immunodeficiency or immuno-suppression caused by acquired or congenital diseases or caused by treatments such as chronic administration (> 14 days) of systemic, i.e. parenteral or oral, corticosteroids (> 5 mg prednisone [or equivalent] per day), radiation or immune-modifying drugs.
- Periodic steroid injections, e.g. intraarticular, are not allowed within 30 days prior to the first vaccination and throughout the study until Visit 5 (V5).
- Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy.
- 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 prevent the subject from complying with study requirements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IMVAMUNETwo s.c. vaccinations with 0.5 ml IMVAMUNE® vaccine containing 1 x 10E8 TCID50 / dose | Biological | Group 1 |
| IMVAMUNEOne s.c. vaccination with placebo (0.5 ml saline), followed by a second s.c. vaccination with 0.5 ml IMVAMUNE® vaccine containing 1 x 10E8 TCID50 | Biological | Group 2 |
Primary outcome
Related Serious Adverse Events
Time frame: within 8 weeks
Incidence of Serious Adverse Events (SAEs) probably, possibly or definitely related to the trial vaccine
13 secondary outcomes
Unsolicited Non-serious AEs: Intensity
Time frame: within 29 days after any vaccination
Unsolicited Non-serious AEs: Relationship to Vaccination
Time frame: within 29 days after any vaccination
Related Grade >=3 Adverse Events
Time frame: within 29 days after any vaccination
Cardiac Signs or Symptoms
Time frame: within 32 weeks
Solicited Local Adverse Events
Time frame: within 8 days after any vaccination
Solicited General Adverse Events
Time frame: within 8 days after any vaccination
ELISA Response Rate
Time frame: within 32 weeks
ELISA Seroconversion Rate
Time frame: within 32 weeks
ELISA GMT
Time frame: within 32 weeks
PRNT Response Rate
Time frame: within 32 weeks
PRNT Seroconversion Rate
Time frame: within 32 weeks
PRNT GMT
Time frame: within 32 weeks
Correlation PRNT vs ELISA Titers
Time frame: within 32 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27327616Greenberg RN, Hay CM, Stapleton JT, Marbury TC, Wagner E, Kreitmeir E, Roesch S, von Krempelhuber A, Young P, Nichols R, Meyer TP, Schmidt D, Weigl J, Virgin G, Arndtz-Wiedemann N, Chaplin P. A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN(R)) in 56-80-Year-Old Subjects. PLoS One. 2016 Jun 21;11(6):e0157335. doi: 10.1371/journal.pone.0157335. eCollection 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard N Greenberg, MD principal investigator
University of Kentucky
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IMVAMUNE in people with Smallpox, run by Bavarian Nordic at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Related Serious Adverse Events (time frame: within 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00857493, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2019.