A Trial to Evaluate Immunogenicity and Safety of Three Co... | NCT01144637

Label	Type	Description	Intervention Names
Group 1	Experimental	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1	Biological: IMVAMUNE®
Group 2	Experimental	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2	Biological: IMVAMUNE®
Group 3	Experimental	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3	Biological: IMVAMUNE®
Group 4	Placebo Comparator	Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS)	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
IMVAMUNE®	Biological	0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)	Group 1 Group 2 Group 3

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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
PRNT Seroconversion Rate

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Turner Overton, MD	Division of Infectious Diseases University of Alabama at Birmingham	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Alabama Vaccine Research Clinic		Birmingham	Alabama	35294	United States
Anaheim Clinical Trials

PubMed Identifier	Type	Citation	Retractions
29652929	Derived	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.

ID	Title	Description
FG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
FG001	Group 2

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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'.

Per-protocol Set

Posted

Geometric Mean

95% Confidence Interval

Titer

2 weeks following the second vaccination

ID	Title	Description
OG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG003	Group 4	Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS) Placebo: 0.5 ml TBS

Units	Counts
Participants	OG000637 OG001628 OG002641 OG003

Title

Denominators

Categories

Title	Measurements
	OG000110.7(103.4 to 118.4) OG001100.5(93.7 to 107.8) OG002117.2(109.0 to 126.0) OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						GMT ratio (Group 1 / Group 2)	1.1012			2-Sided	95	0.9992	1.2136					Equivalence	The equivalence margins to show that the 3 vaccine lots are equivalent in terms of PRNT GMTs at Week 6 was predefined as [0.5; 2] for the GMT ratios (pairwise)
OG000 OG002

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'.

Per-protocol Set

Posted

Geometric Mean

95% Confidence Interval

Titer

2 weeks following the second vaccination

ID	Title	Description
OG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG003	Group 4	Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS) Placebo: 0.5 ml TBS

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.

Per-protocol Set

Posted

Number

95% Confidence Interval

percentage of subjects

2 weeks following the second vaccination

ID	Title	Description
OG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG003

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.

Per-protocol Set

Posted

Number

95% Confidence Interval

percentage of subjects

2 weeks following the second vaccination

ID	Title	Description
OG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG003

Secondary

Correlation PRNT vs ELISA Titers

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

Per-protocol Set

Posted

Number

95% Confidence Interval

Pearson correlation coefficient

2 weeks following the second vaccination

ID	Title	Description
OG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG003	Group 4	Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS) Placebo: 0.5 ml TBS

Secondary

Serious Adverse Events

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

Full Analysis Set

Posted

Count of Participants

Participants

within 30 weeks

ID	Title	Description
OG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG003	Group 4	Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS) Placebo: 0.5 ml TBS

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)

Full Analysis Set

Posted

Count of Participants

Participants

within 30 weeks

ID	Title	Description
OG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG003

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

Full Analysis Set

Posted

Count of Participants

Participants

within 29 days after any vaccination

ID	Title	Description
OG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG003	Group 4	Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS) Placebo: 0.5 ml TBS

Secondary

Unsolicited Non-serious AEs: Intensity

Occurrence of unsolicited non-serious AEs by Intensity

Full Analysis Set

Posted

Number

events

within 29 days after any vaccination

ID	Title	Description
OG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG003	Group 4	Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS) Placebo: 0.5 ml TBS

Secondary

Unsolicited Non-serious AEs: Relationship to Vaccination

Occurrence of unsolicited non-serious AEs by relationship to study vaccine

Full Analysis Set

Posted

Number

events

within 29 days after any vaccination

ID	Title	Description
OG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG003	Group 4	Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS) Placebo: 0.5 ml TBS

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.

Full Analysis Set

Posted

Count of Participants

Participants

within 8 days after any vaccination

ID	Title	Description
OG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG003	Group 4	Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS) Placebo: 0.5 ml TBS

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.

Full Analysis Set

Posted

Count of Participants

Participants

within 8 days after any vaccination

ID	Title	Description
OG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OG003	Group 4	Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS) Placebo: 0.5 ml TBS

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Colitis	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0010 affected1,005 at risk EG0021 affected999 at risk EG0030 affected1,002 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0010 affected1,005 at risk EG0021 affected999 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Hiatus hernia	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0011 affected1,005 at risk EG0020 affected999 at risk EG003
Chest pain	General disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Abscess limb	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0010 affected1,005 at risk EG0021 affected999 at risk EG003
Appendicitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0012 affected1,005 at risk EG0021 affected999 at risk EG003
Appendicitis perforated	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Meningitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0010 affected1,005 at risk EG0021 affected999 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Concussion	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0001 affected999 at risk EG0011 affected1,005 at risk EG0020 affected999 at risk EG003
Excoriation	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0011 affected1,005 at risk EG0020 affected999 at risk EG003
Hodgkin's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0001 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Ataxia	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0011 affected1,005 at risk EG0020 affected999 at risk EG003
Convulsion	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Headache	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Neurological symptom	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Syncope	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0010 affected1,005 at risk EG0021 affected999 at risk EG003
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0010 affected1,005 at risk EG0021 affected999 at risk EG003
Foetal death	Pregnancy, puerperium and perinatal conditions	MedDRA 15.1	Systematic Assessment	EG0001 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Completed suicide	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Depression	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0011 affected1,005 at risk EG0020 affected999 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected999 at risk EG0010 affected1,005 at risk EG0021 affected999 at risk EG003
Thrombophlebitis superficial	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected999 at risk EG0010 affected1,005 at risk EG0020 affected999 at risk EG003

ID	Term
D011213	Poxviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D007239	Infections

ID	Title	Description
BG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
BG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
BG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
BG003	Group 4	Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS) Placebo: 0.5 ml TBS
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group 1	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)	1	999	11	999	53	999
EG001	Group 2	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)	0	1,005	7	1,005	70	1,005
EG002	Group 3	Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3 IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)	0	999	7	999	65	999
EG003	Group 4	Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS) Placebo: 0.5 ml TBS	0	1,002	8	1,002	48	1,002

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Injection site haematoma	General disorders	MedDRA 15.1	Systematic Assessment	EG0005 affected999 at risk EG00111 affected1,005 at risk EG0028 affected999 at risk EG0035 affected1,002 at risk
Injection site induration	General disorders	MedDRA 15.1	Systematic Assessment	EG00014 affected999 at risk EG00115 affected1,005 at risk EG00221 affected999 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG00011 affected999 at risk EG00114 affected1,005 at risk EG00211 affected999 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG00017 affected999 at risk EG00121 affected1,005 at risk EG00220 affected999 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0009 affected999 at risk EG0019 affected1,005 at risk EG0026 affected999 at risk EG003