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

Smallpox Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01144637
• Other study ID #: POX-MVA-013
• Status: Completed
• Phase: Phase 3
• Start date: February 2013
• Est. completion date: June 2014

Study information

• Verified date: December 2018
• Source: Bavarian Nordic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4005
• Est. completion date: June 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• 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

• 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)

Exclusion criteria

• 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

• 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

Related Conditions & MeSH terms

• Smallpox
• Vaccinia

Intervention

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

Other:
• Placebo
0.5 ml TBS

Locations

Country	Name	City	State
United States	Anaheim Clinical Trials	Anaheim	California
United States	Heartland Research Associates	Augusta	Kansas
United States	Alabama Vaccine Research Clinic	Birmingham	Alabama
United States	Holston Medical Group	Bristol	Tennessee
United States	Rapid Medical Research, Inc.	Cleveland	Ohio
United States	Lynn Institute of the Rockies	Colorado Springs	Colorado
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Benchmark Research	Fort Worth	Texas
United States	Broward Research Group	Hollywood	Florida
United States	University Physicians Internal Medicine University Physicians & Surgeons, Inc.	Huntington	West Virginia
United States	Volunteer Research Group	Knoxville	Tennessee
United States	Clinical Research Center of Nevada, LLC	Las Vegas	Nevada
United States	Tanner Clinic	Layton	Utah
United States	National Research Institute	Los Angeles	California
United States	Accelovance Melbourne	Melbourne	Florida
United States	Advanced Clinical Research, Inc.	Meridian	Idaho
United States	Benchmark Research	Metairie	Louisiana
United States	PMG Research of Charleston	Mount Pleasant	South Carolina
United States	Clinical Research Associates of Tidewater	Norfolk	Virginia
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Meridian Clinical Research, LLC	Omaha	Nebraska
United States	Accelovance Peoria	Peoria	Illinois
United States	Columbia Research Group, Inc.	Portland	Oregon
United States	Wake Research Associates	Raleigh	North Carolina
United States	Northern California Clinical Research Center (NCCRC)	Redding	California
United States	Rochester Clinical Research, Inc.	Rochester	New York
United States	Washington University in St. Louis, School of Medicine	Saint Louis	Missouri
United States	Therapeutics Clinical Research	San Diego	California
United States	Southeast Regional Research Group	Savannah	Georgia
United States	QPS Bio-Kinetic	Springfield	Missouri
United States	Omega Medical Research	Warwick	Rhode Island
United States	Advanced Clinical Research	West Jordan	Utah
United States	Heartland Research Associates, LLC	Wichita	Kansas
United States	Family Practice Center of Wooster	Wooster	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Bavarian Nordic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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'.	2 weeks following the second vaccination
Secondary	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'.	2 weeks following the second vaccination
Secondary	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.	2 weeks following the second vaccination
Secondary	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.	2 weeks following the second vaccination
Secondary	Correlation PRNT vs ELISA Titers	Pearson Correlation Coefficient between the log10 transformed PRNT titers and the log10 transformed ELISA titers	2 weeks following the second vaccination
Secondary	Serious Adverse Events	Incidence, relationship and intensity of any Serious Adverse Event (SAE)	within 30 weeks
Secondary	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)	within 30 weeks
Secondary	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	within 29 days after any vaccination
Secondary	Unsolicited Non-serious AEs: Intensity	Occurrence of unsolicited non-serious AEs by Intensity	within 29 days after any vaccination
Secondary	Unsolicited Non-serious AEs: Relationship to Vaccination	Occurrence of unsolicited non-serious AEs by relationship to study vaccine	within 29 days after any vaccination
Secondary	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.	within 8 days after any vaccination
Secondary	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.	within 8 days after any vaccination