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SmallpoxPhase 3NCT01144637

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

A Phase 3 study testing IMVAMUNE® in people with Smallpox, run by Bavarian Nordic at 34 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

A randomized, double-blind, placebo-controlled Phase III trial to evaluate immunogenicity and safety of three consecutive production lots of IMVAMUNE® (MVA-BN®) smallpox vaccine in healthy, vaccinia-naïve subjects. Read more about this study

Who is it for?
Ages 18 to 40 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?
Yes, some participants may receive a placebo
How many people
4,005 participants
Where
34 sitesUnited States
Study dates
Feb 2013to Jun 2014
Phase
Phase 3
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 40 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Male and female subjects, 18 to 40 years of age
  • The subject has read, signed and dated the informed consent form, having been advised of the risks and benefits of the trial in a language understood by the subject and prior to performance of any trial specific procedures
  • BMI ≥ 18.5 and < 35
  • Women of childbearing potential (WOCBP) must have used an acceptable method of contraception for 30 days prior to the first vaccination, must agree to use an acceptable method of contraception during the trial, and must avoid becoming pregnant for at least 28 days after the last vaccination. A woman is considered of childbearing potential unless post-menopausal or with a history of hysterectomy (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products)
  • WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to each vaccination
  • White blood cells ≥ 2,500/mm3 < ULN
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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:
  • a. Total bilirubin ≤ 1.5 x ULN in the absence of other evidence of significant liver disease
  • b. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 1.5 x ULN
  • 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 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 prior to 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
  • History of or active autoimmune disease, persons with vitiligo or thyroid disease taking thyroid replacement are not excluded
  • Known or suspected impairment of immunologic function including, but not limited to, HIV Infection, clinically significant liver disease (including chronic active HBV or HCV), diabetes mellitus, moderate to severe kidney impairment
  • History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure. Subjects with history of skin cancer must not be vaccinated at the previous tumor site
  • History or clinical manifestation of clinically significant and severe hematological, pulmonary, central nervous, cardiovascular or gastrointestinal disorders
  • Clinically significant mental disorder not adequately controlled by medical treatment
  • History of coronary heart disease, myocardial infarction, angina pectoris, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, or any other heart condition under the care of a doctor
  • Known history of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before age 50 years
  • Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's risk assessment tool (http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof) NOTE: This criterion applies only to subjects 20 years of age and older
  • 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 know allergy to egg or aminoglycosides
  • History of anaphylaxis or severe allergic reaction to any vaccine
  • Acute disease (illness with or without a fever) at the time 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 to or after trial vaccination
  • Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior to 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 (V5)
  • 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 (V5)
  • 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
  • Trial personnel

Trial locations and contacts

34 sites in 1 country.

34 sites in 1 country

United States34 sites

  • Anaheim Clinical Trials

    Anaheim, California, 92801

  • Heartland Research Associates

    Augusta, Kansas, 67010

  • Alabama Vaccine Research Clinic

    Birmingham, Alabama, 35294

  • Holston Medical Group

    Bristol, Tennessee, 37620

  • Rapid Medical Research, Inc.

    Cleveland, Ohio, 44122

  • Lynn Institute of the Rockies

    Colorado Springs, Colorado, 80907

  • Avail Clinical Research, LLC

    DeLand, Florida, 32720

  • Benchmark Research

    Fort Worth, Texas, 76135

  • Broward Research Group

    Hollywood, Florida, 33024

  • University Physicians Internal Medicine University Physicians & Surgeons, Inc.

    Huntington, West Virginia, 25701

  • Volunteer Research Group

    Knoxville, Tennessee, 37920

  • Clinical Research Center of Nevada, LLC

    Las Vegas, Nevada, 89104

  • Tanner Clinic

    Layton, Utah, 84041

  • National Research Institute

    Los Angeles, California, 90057

  • Accelovance Melbourne

    Melbourne, Florida, 32935

  • Advanced Clinical Research, Inc.

    Meridian, Idaho, 83642

  • Benchmark Research

    Metairie, Louisiana, 70006

  • PMG Research of Charleston

    Mt. Pleasant, South Carolina, 29464

  • Clinical Research Associates of Tidewater

    Norfolk, Virginia, 23507

  • Lynn Health Science Institute

    Oklahoma City, Oklahoma, 73112

  • Meridian Clinical Research, LLC

    Omaha, Nebraska, 68134

  • Accelovance Peoria

    Peoria, Illinois, 61602

  • Columbia Research Group, Inc.

    Portland, Oregon, 97239

  • Wake Research Associates

    Raleigh, North Carolina, 27612

  • Northern California Clinical Research Center (NCCRC)

    Redding, California, 96001

  • Rochester Clinical Research, Inc.

    Rochester, New York, 14609

  • Therapeutics Clinical Research

    San Diego, California, 92123

  • Southeast Regional Research Group

    Savannah, Georgia, 31405

  • QPS Bio-Kinetic

    Springfield, Missouri, 65802

  • Washington University in St. Louis, School of Medicine

    St Louis, Missouri, 63110

  • Omega Medical Research

    Warwick, Rhode Island, 02886

  • Advanced Clinical Research

    West Jordan, Utah, 84088

  • Heartland Research Associates, LLC

    Wichita, Kansas, 67207

  • Family Practice Center of Wooster

    Wooster, Ohio, 44691

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial to Evaluate Immunogenicity and Safety of Three Consecutive Production Lots of IMVAMUNE® (MVA-BN®) Smallpox Vaccine in Healthy, Vaccinia-Naïve Subjects

A randomized, double-blind, placebo-controlled Phase III trial to evaluate immunogenicity and safety of three consecutive production lots of IMVAMUNE® (MVA-BN®) smallpox vaccine in healthy, vaccinia-naïve subjects.

Conditions
Smallpox
Being tested
IMVAMUNE®, Placebo
Medical subject headings
Smallpox

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IMVAMUNE®Biological

    Also called IMVANEX, MVA-BN®

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

  • PlaceboOther

    Also called Tris-buffered-saline

    0.5 ml TBS

Study groups in NCT01144637
Study groupRoleWhat they receive
Group 1ExperimentalTwo vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1
Receives: Biological: IMVAMUNE®
Group 2ExperimentalTwo vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2
Receives: Biological: IMVAMUNE®
Group 3ExperimentalTwo vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3
Receives: Biological: IMVAMUNE®
Group 4Placebo comparatorTwo vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS)
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PRNT GMT

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

    Measured: 2 weeks following the second vaccination

Secondary outcomes (11)

  1. 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: 2 weeks following the second vaccination

  2. PRNT Seroconversion Rate

    Seroconversion rate based on 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: 2 weeks following the second vaccination

  3. ELISA Seroconversion Rate

    Seroconversion rate based on 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: 2 weeks following the second vaccination

  4. Correlation PRNT vs ELISA Titers

    Pearson Correlation Coefficient between the log10 transformed PRNT titers and the log10 transformed ELISA titers

    Measured: 2 weeks following the second vaccination

  5. Serious Adverse Events

    Incidence, relationship and intensity of any Serious Adverse Event (SAE)

    Measured: within 30 weeks

  6. Cardiac Signs or Symptoms

    Incidence, relationship and intensity of any cardiac sign or symptom indicating a case of myo-/pericarditis (Adverse Event of Special Interest (AESI)).

    An AESI was defined in this trial as:

    • Any cardiac sign or symptom developed since the first vaccination
    • ECG changes determined to be clinically significant
    • Cardiac enzyme Troponin I >= 2 x ULN (>= Grade 2)

    Measured: within 30 weeks

  7. Related Grade >=3 Adverse Events

    Incidence of any Grade >=3 Adverse Events probably, possibly or definitely related to the trial vaccine. Pooled solicited (general only) and unsolicited AEs

    Measured: within 29 days after any vaccination

  8. Unsolicited Non-serious AEs: Intensity

    Occurrence of unsolicited non-serious AEs by Intensity

    Measured: within 29 days after any vaccination

  9. 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

  10. Solicited Local AEs

    Incidence and intensity of solicited local AEs (redness, swelling, induration, pruritus and pain). Percentages based on subjects with at least one completed diary card.

    Measured: within 8 days after any vaccination

  11. Solicited General AEs

    Incidence of solicited general AEs (pyrexia, headache, myalgia, chills, nausea, and fatigue): Intensity and relationship to vaccination. Percentages based on subjects with at least one completed diary card.

    Measured: within 8 days after any vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2010 (estimated)
  2. Study startFeb 2013
  3. Primary completionNov 2013
  4. Study completionJun 2014

Resources

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 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
4,005 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01144637
Sponsor's protocol ID
POX-MVA-013
Status last verified
Dec 2018
First submitted
14 Jun 2010
Last updated
3 Jan 2019
Data monitoring committee
Yes

Publications

  • Overton ET, Lawrence SJ, Wagner E, Nopora K, Rosch S, Young P, Schmidt D, Kreusel C, De Carli S, Meyer TP, Weidenthaler H, Samy N, Chaplin P. Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial. PLoS One. 2018 Apr 13;13(4):e0195897. doi: 10.1371/journal.pone.0195897. eCollection 2018.

    PubMed 29652929

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing IMVAMUNE® in people with Smallpox, run by Bavarian Nordic at 34 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 3 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 34 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 3 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?

PRNT GMT (time frame: 2 weeks following the second vaccination). 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 NCT01144637, 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 3 Jan 2019.

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