SmallpoxPhase 2NCT01668537
A Phase II Trial to Compare a Liquid-frozen and a Freeze-dried Formulation of IMVAMUNE (MVA-BN®) Smallpox Vaccine in Vaccinia-naïve Healthy Subjects
A Phase 2 study testing LF formulation of IMVAMUNE® and FD formulation of IMVAMUNE® in people with Smallpox, run by Bavarian Nordic at 3 sites in United States.
Trial summary
A randomized, double-blind, multicenter Phase II trial to compare the immunogenicity and safety of a liquid-frozen and a freeze-dried formulation of IMVAMUNE (MVA-BN®) smallpox vaccine in vaccinia-naïve healthy subjects Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Smallpox
- What is being tested?
- LF formulation of IMVAMUNE® and FD formulation of IMVAMUNE®
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 651 participants
- Where
- 3 sitesUnited States
- Study dates
- Mar 2013to Jun 2014
- 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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male and female subjects, 18-55 years of age
- The subject has read, signed and dated 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 and has signed the Health Insurance Portability and Accountability Act (HIPAA) authorization form
- Body Mass Index (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 (SCR) and a negative urine pregnancy test within 24 hours prior to each vaccination
- White blood cells ≥ 2500/mm3 and < ULN
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- 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:
- 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
- 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 (PVC) in a row, ST elevation consistent with ischemia
Who cannot join
- Typical vaccinia scar
- Known or suspected history of smallpox vaccination
- History of vaccination with any poxvirus-based vaccine
- US Military service before 1991 or after January 2003
- Pregnant or breast-feeding women
- Uncontrolled serious infection, i.e. not responding to antimicrobial therapy
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- 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 in the opinion of the investigator
- History of or active autoimmune disease, persons with vitiligo or thyroid disease taking thyroid hormone 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 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, 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 has had onset of ischemic heart disease before the age of 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 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 known allergy to egg or aminoglycoside (gentamycin)
- History of anaphylaxis or severe allergic reaction to any vaccine
- Acute disease (illness with or without a fever) at the time of 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 or after trial vaccination
- Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior 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 (Visit 5)
- 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 (Visit 5)
- 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 (with the day of the FU call being considered the last day of the trial period).
- Trial personnel
Trial locations and contacts
3 sites in 1 country.
United States3 sites
PRA
Lenexa, Kansas, 66219
University of Kentucky
Lexington, Kentucky, 40536
Miami Research Associates
South Miami, Florida, 33143
About this study
Official title: A Randomized, Double-blind, Multicenter Phase II Trial to Compare the Immunogenicity and Safety of a Liquid-frozen and a Freeze-dried Formulation of IMVAMUNE® (MVA-BN®) Smallpox Vaccine in Vaccinia-naïve Healthy Subjects
A randomized, double-blind, multicenter Phase II trial to compare the immunogenicity and safety of a liquid-frozen and a freeze-dried formulation of IMVAMUNE (MVA-BN®) smallpox vaccine in vaccinia-naïve healthy subjects
- Conditions
- Smallpox
- Being tested
- LF formulation of IMVAMUNE®, FD formulation of IMVAMUNE®
- Medical subject headings
- Smallpox
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LF formulation of IMVAMUNE®Biological
FD formulation of IMVAMUNE®Biological
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | LF formulation of IMVAMUNE® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart Receives: Biological: LF formulation of IMVAMUNE® |
| Group 2 | Experimental | FD formulation of IMVAMUNE® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart Receives: Biological: FD formulation of IMVAMUNE® |
What is being measured
The primary outcome is the main question the study is designed to answer.
ELISA GMT
Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Titers below the detection limit are included with a value of '1'
Measured: Week 6
Secondary outcomes (17)
Number of Participants With Serious Adverse Events
Occurrence, relationship to the trial vaccine and intensity of any Serious Adverse Event (SAE).
Measured: up to 32 weeks
Number of Participants With Adverse Events of Special Interest (AESI)
Occurrence, relationship to the trial vaccine and intensity of any Adverse Event of Special Interest (AESI). AESIs were defined as any cardiac symptoms and ECG changes determined to be clinically significant or cardiac enzyme troponin I elevated above 2 x the Upper Limit of Normal
Measured: up to 32 weeks
Number of Participants With Related Grade >=3 Adverse Events
Occurrence of any Grade >=3 Adverse Events related to the trial vaccine.
Measured: within 29 days after vaccination
Number of Participants With Unsolicited Adverse Events
Occurrence, relationship to the trial vaccine and intensity of unsolicited treatment-emergent AEs (TEAEs).
Measured: within 29 days after vaccination
Number of Participants With Solicited Local Averse Events
Occurrence and intensity of solicited local AEs (redness, swelling, induration, pruritus and pain) during the 8-day period (day of vaccination and the following 7 days) after any vaccination. Events were graded by intensity (1 = mild, 2 = moderate, 3 = severe).
Measured: 8 days after any vaccination
Number of Participants With Solicited General Adverse Events
Occurrence, intensity and relationship to the trial vaccines of solicited general AEs (pyrexia, headache, myalgia, nausea, fatigue and chills) during the 8-day period (day of vaccination and the following 7 days) after any vaccination. Events were graded by intensity (1 = mild, 2 = moderate, 3 = severe).
Measured: within 8 days after any vaccination
ELISA GMTs
Geometric Mean Titers (GMT) at all immunogenicity sampling time points based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). For the calculation of GMTs all measurements are included as they provide meaningful information even if below the detection limit (DL). Disregarding these measurements would highly bias the reported GMTs. We imputed values <DL as a value of '1' and the GMT and corresponding 95% confidence intervals were calculated.
Measured: within 8 weeks
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'
Measured: Week 6
PRNT GMTs
Geometric Mean Titers (GMT) at all immunogenicity sampling time points based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). For the calculation of GMTs all measurements are included as they provide meaningful information even if below the detection limit (DL). Disregarding these measurements would highly bias the reported GMTs. We imputed values <DL as a value of '1' and the GMT and corresponding 95% confidence intervals were calculated.
Measured: within 8 weeks
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.
Measured: Week 6
Percentage of Participants With Seroconversion by ELISA
Seroconversion rates at all post-baseline immunogenicity sampling time points 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.
Measured: within 8 weeks
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 (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects.
Measured: Week 6
Percentage of Participants With Seroconversion by PRNT
Seroconversion rates at all post-baseline immunogenicity sampling time points based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (2) 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.
Measured: within 8 weeks
ELISPOT Magnitudes of Response
Magnitudes of response of IFNγ producing T-cells measured by vaccinica-specific ELISPOT. Spot Forming Units below the detection limit are included as a value of '1'.
Measured: within 8 weeks
Percentage of Participants With Response by ELISPOT
Response rates regarding IFNγ producing T-cells measured by vaccinia-specific ELISPOT. A response to the vaccine was defined as either the appearance of a positive signal for participants without a positive signal at Baseline or an increase by a factor of at least 1.7 of the SFU/1 x 10E6 PBMC compared to the Baseline SFU/1 x 10E6 PBMC for participants with a positive signal at Baseline.
Measured: within 8 weeks
Percentage of Responders by ELISPOT
Responder rate measured by vaccinia specific ELISPOT. A participant was defined as a responder to the vaccine determined by ELISPOT if the participant had at least 1 post-baseline visit determined to be a response. A response to the vaccine was defined as either the appearance of a positive signal for participants without a positive signal at Baseline or an increase by a factor of at least 1.7 of the SFU/1 x 10E6 PBMC compared to the Baseline SFU/1 x 10E6 PBMC for participants with a positive signal at Baseline.
Measured: within 8 weeks
Correlation ELISA vs PRNT Titers
Pearson Correlation Coefficient between the ELISA titers and the PRNT titers at weeks 4, 6 and 8 based on the log10 transformed titer values
Measured: within 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2012 (estimated)
- Study startMar 2013
- Primary completionJan 2014
- Study completionJun 2014
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.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 651 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
- NCT01668537
- Sponsor's protocol ID
- POX-MVA-027
- Status last verified
- Oct 2020
- First submitted
- 14 Aug 2012
- Last updated
- 12 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Multicenter Phase II Trial to Compare the Immunogenicity and Safety of a Liquid-frozen and a Freeze-dried Formulation of IMVAMUNE® (MVA-BN®) Smallpox Vaccine in Vaccinia-naïve Healthy Subjects
- ClinicalTrials.gov ID
- NCT01668537
- Acronym / sponsor ID
- POX-MVA-027
- Conditions
- Smallpox
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 651 participants (actual)
- Lead sponsor
- Bavarian NordicIndustry (pharma, biotech, devices)
- Study start
- Mar 2013
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 20 Aug 2012 (estimated)
- Results
- Posted 12 Oct 2020
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, multicenter Phase II trial to compare the immunogenicity and safety of a liquid-frozen and a freeze-dried formulation of IMVAMUNE (MVA-BN®) smallpox vaccine in vaccinia-naïve healthy subjects
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Biological: LF formulation of IMVAMUNE®LF formulation of IMVAMUNE® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart |
| Group 2 | Experimental | Biological: FD formulation of IMVAMUNE®FD formulation of IMVAMUNE® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- Male and female subjects, 18-55 years of age
- The subject has read, signed and dated 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 and has signed the Health Insurance Portability and Accountability Act (HIPAA) authorization form
- Body Mass Index (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 (SCR) and a negative urine pregnancy test within 24 hours prior to each vaccination
Key exclusion criteria (27 listed)
- Typical vaccinia scar
- Known or suspected history of smallpox vaccination
- History of vaccination with any poxvirus-based vaccine
- US Military service before 1991 or after January 2003
- Pregnant or breast-feeding women
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 |
|---|---|---|
| LF formulation of IMVAMUNE® | Biological | Group 1 |
| FD formulation of IMVAMUNE® | Biological | Group 2 |
Primary outcome
ELISA GMT
Time frame: Week 6
Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Titers below the detection limit are included with a value of '1'
17 secondary outcomes
Number of Participants With Serious Adverse Events
Time frame: up to 32 weeks
Number of Participants With Adverse Events of Special Interest (AESI)
Time frame: up to 32 weeks
Number of Participants With Related Grade >=3 Adverse Events
Time frame: within 29 days after vaccination
Number of Participants With Unsolicited Adverse Events
Time frame: within 29 days after vaccination
Number of Participants With Solicited Local Averse Events
Time frame: 8 days after any vaccination
Number of Participants With Solicited General Adverse Events
Time frame: within 8 days after any vaccination
ELISA GMTs
Time frame: within 8 weeks
PRNT GMT
Time frame: Week 6
PRNT GMTs
Time frame: within 8 weeks
Percentage of Participants With Seroconversion by ELISA
Time frame: Week 6
Percentage of Participants With Seroconversion by ELISA
Time frame: within 8 weeks
Percentage of Participants With Seroconversion by PRNT
Time frame: Week 6
Percentage of Participants With Seroconversion by PRNT
Time frame: within 8 weeks
ELISPOT Magnitudes of Response
Time frame: within 8 weeks
Percentage of Participants With Response by ELISPOT
Time frame: within 8 weeks
Percentage of Responders by ELISPOT
Time frame: within 8 weeks
Correlation ELISA vs PRNT Titers
Time frame: within 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Smallpox
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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
3 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 LF formulation of IMVAMUNE® and FD formulation of IMVAMUNE® in people with Smallpox, run by Bavarian Nordic at 3 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 17 inclusion and 27 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 12 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 12 Oct 2020). 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?
ELISA GMT (time frame: Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Oct 2020.