Freeze-Dried MVA-BN® Lot Consistency Smallpox Trial

• Sponsor: Bavarian Nordic (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03699124
• Collaborator: Biomedical Advanced Research and Development Authority (U.S. Fed)
• Enrollment: 1,129
• Locations: 12
• Arms: 3
• Actual Duration (Months): 12.1
• Patients Per Site: 94.1
• Patients Per Site Per Month: 7.8

Study Details

Study Description

Brief Summary

This is a Phase 3 multicenter trial to evaluate safety and immune response of three consecutive production lots of freeze-dried (FD) MVA-BN smallpox vaccine. The vaccine will be given to healthy subjects who do not have a smallpox scar.

Approximately 1110 subjects will be randomly enrolled into one of three groups:

Group 1 will include 370 subjects, who will receive two separate injections (shot) with a short needle, given below the skin of the upper arm with 0.5 mL FD MVA-BN (Lot 1).

Group 2 will include 370 subjects, who will receive two separate injections (shot) with a short needle, given below the skin of the upper arm with 0.5 mL FD MVA-BN (Lot 2).

Group 3 will include 370 subjects, who will receive two separate injections (shot) with a short needle, given below the skin of the upper arm with 0.5 mL FD MVA-BN (Lot 3).

The primary objective of the trial is to show that the immune response elicited (produced) by three consecutively produced MVA-BN lots are statistically (numerically) comparable.

Condition or Disease	Intervention/Treatment	Phase
Smallpox	Biological: FD MVA-BN	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-blind, Multicenter Phase III Trial to Evaluate Immunogenicity and Safety of Three Consecutive Production Lots of a Freeze-dried Formulation of MVA-BN® Smallpox Vaccine in Healthy, Vaccinia-naïve Subjects
• Actual Study Start Date: Jun 19, 2019
• Actual Primary Completion Date: Jan 6, 2020
• Actual Study Completion Date: Jun 22, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: GP 1: two doses of FD MVA-BN--Lot 1 Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1	Biological: FD MVA-BN; Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Active Comparator: GP 2: two doses of FD MVA-BN--Lot 2 Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2	Biological: FD MVA-BN; Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Active Comparator: GP 3: two doses of FD MVA-BN--Lot 3 Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3	Biological: FD MVA-BN; Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)

Outcome Measures

Primary Outcome Measures

1. Vaccinia-Specific Neutralizing Antibodies Measured by Plaque Reduction Neutralization Test (PRNT) [Two weeks post second vaccination; approximately Week 6.]

   Vaccinia-specific neutralizing antibody titers below the lower limit of quantitation are given a value 10, i.e., half of the PRNT lower limit of quantitation of 20.

Secondary Outcome Measures

1. Vaccinia-Specific Total Antibodies Measured by Enzyme-Linked Immunosorbant Assay (ELISA) [Two weeks post second vaccination; approximately Week 6.]

   Vaccinia-specific total antibody titers below the lower limit of quantitation are given a value 100, i.e., half of the ELISA lower limit of quantitation of 200.

2. Seroconversion Rates for Vaccinia-Specific Neutralizing Antibodies by PRNT [Two weeks post second vaccination; approximately Week 6.]

   Seroconversion is defined as either the appearance of antibody titers >= LLOQ for subjects with a titer below LLOQ at baseline, or a doubling (or more) of the antibody titer compared to the baseline titer for subjects with a titer equal or above the LLOQ at baseline. The LLOQ for PRNT is 20.

3. Seroconversion Rates for Vaccinia-Specific Total Antibodies by ELISA [Two weeks post second vaccination; approximately Week 6.]

   Seroconversion is defined as either the appearance of antibody titers >= LLOQ for subjects with a titer below LLOQ at baseline, or a doubling (or more) of the antibody titer compared to the baseline titer for subjects with a titer equal or above the LLOQ at baseline. The LLOQ for ELISA is 200.

4. Pearson Correlation Coefficient Between the log10 Transformed PRNT Titers and the log10 Transformed ELISA Titers [Two weeks post second vaccination; approximately Week 6.]

   Pearson correlation coefficient calculated on the log10 PRNT vs. ELISA titers at 2 weeks post second vaccination.

5. Occurrence, Relationship and Intensity of Any Serious Adverse Event (SAE) at Any Time During the Trial [Overall study, ie from first vaccination at Visit 1 through the Follow-up Visit approximately 32 weeks post first vaccination.]

   Occurrence is defined as the number of participants who experienced an SAE. Related SAEs are defined as those for which causality to trial vaccine was considered possible, probable, definite, or was missing. Intensity is defined per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, published September 2007, where >= Grade 3 is either Severe or Potentially Life Threatening.

6. Occurrence, Relationship and Intensity of Any Cardiac Sign or Symptom Indicating a Case of Myo-/Pericarditis at Any Time During the Trial. [Overall study, ie from first vaccination at Visit 1 through the Follow-up Visit approximately 32 weeks post first vaccination.]

   Occurrence is defined as the number of participants who experienced an event falling in the system organ class of "Cardiac disorders" per MedDRA version 22.0. Related cardiac signs and symptoms are defined as those for which causality to trial vaccine was considered possible, probable, definite, or was missing. Intensity is defined per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, published September 2007, where >= Grade 3 is either Severe or Potentially Life Threatening.

7. Occurrence of Any Grade 3 or 4 Unsolicited AEs Probably, Possibly or Definitely Related to the Trial Vaccine [Within 28 days (and up to 35 days) after each vaccination, ie, from Visit 1 to Visit 3 for the first vaccination and from Visit 3 to Visit 5 for the second vaccination based on the protocol scheduled visits.]

   Related AEs are defined as those for which causality to trial vaccine was considered possible, probable, definite, or was missing. Intensity is defined per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, published September 2007, where Grade 3 is Severe and Grade 4 is Potentially Life Threatening.

8. Occurrence, Relationship and Intensity of Unsolicited AEs [Within 28 days (and up to 35 days) after each vaccination, ie, from Visit 1 to Visit 3 for the first vaccination and from Visit 3 to Visit 5 for the second vaccination based on the protocol scheduled visits.]

   Occurrence is defined as the number of participants who experienced an unsolicited AE. Related unsolicited AEs are defined as those for which causality to trial vaccine was considered possible, probable, definite, or was missing. Intensity is defined per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, published September 2007, where >= Grade 3 is either Severe or Potentially Life Threatening.

9. 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 each vaccination, ie Days 1-8 for the first vaccination and Days 28-35 for the second vaccination based on the protocol scheduled visits.]

   Occurrence is defined as the number of participants who experienced a solicited local AE. Intensity is defined per the protocol for each local event type. For injection site erythema, swelling, and induration the intensity is graded based on the maximum diameter as Grade 1: < 30mm, Grade 2: >= 30 - < 100mm, Grade 3: >= 100mm. Intensity for pruritis is defined as Grade 1: mild, Grade 2: moderate, Grade 3: severe. Intensity for injection site pain is defined as Grade 1: Painful on touch, Grade 2: Painful when moving the limb, Grade 3: Spontaneously painful/prevents normal activity. If a participant experienced the local event after both vaccinations, the maximum intensity is presented.

10. Duration of Solicited Local AEs (Redness, Swelling, Induration, Pruritus and Pain). [Starting during the 8 day period (day of vaccination and the following 7 days) after each vaccination, ie, Days 1-8 for the first vaccination and Days 28-35 for the second vaccination based on the protocol scheduled visits, through resolution.]

    Number of days from the start of the local event to resolution. If a participant experienced the local event after both vaccinations, the longer duration is presented. Subjects who had a missing resolution date for the event are not included in the analysis.

11. Occurrence, Relationship, and Intensity 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 each vaccination, ie Days 1-8 for the first vaccination and Days 28-35 for the second vaccination based on the protocol scheduled visits.]

    Occurrence is defined as the number of participants who experienced a solicited general AE. Related solicited general AEs are defined as those for which causality to trial vaccine was considered possible, probable, definite, or was missing. Intensity is defined per the protocol for each general event type. For pyrexia (increased body temperature) grading is defined as Grade 1: ≥ 99.5 - < 100.4°F (≥ 37.5 - < 38.0°C), Grade 2:≥ 100.4 - < 102.2°F (≥ 38.0 - < 39.0°C), Grade 3:≥ 102.2 - < 104°F (≥ 39.0 - < 40.0°C), and Grade 4: ≥ 104°F (≥ 40.0°C). Intensity for headache, myalgia, nausea, fatigue and chills is defined as Grade 1: mild, Grade 2: moderate, Grade 3: severe. If a participant experienced the general event after both vaccinations, the maximum intensity is presented.

12. Duration of Solicited General AEs (Pyrexia [Body Temperature Increase], Headache, Myalgia, Nausea, Fatigue and Chills) [Starting during the 8 day period (day of vaccination and the following 7 days) after each vaccination, ie, Days 1-8 for the first vaccination and Days 28-35 for the second vaccination based on the protocol scheduled visits, through resolution.]

    Number of days from the start of the general event to resolution. If a participant experienced the general event after both vaccinations, the longer duration is presented. Subjects who had a missing resolution date for the event are not included in the analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• The subject has read, signed and dated the ICF

• Body Mass Index ≥ 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 (defined as ≥ 12 months without a menstrual period) or surgically sterilized. 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 (please note: a negative urine pregnancy test is required within 24 hours prior to each vaccination)

• White blood cells ≥ 2500/mm3 < ULN (Upper Limit of Normal)

• 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: (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72) = CrCl (mL/min). For women the result, calculated with the above formula, has to be multiplied by 0.85 = CrCl (mL/min)

• Adequate hepatic function defined as: Total bilirubin ≤ 1.5 x ULN in the absence of other evidence of significant liver disease Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 1.5 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, human immunodeficiency virus (HIV) Infection, clinically significant liver disease (including chronic active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection), diabetes mellitus

• 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

• Abnormal Troponin I level > ULN

• Known history of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before age 50 years

• Active or history of chronic alcohol abuse and/or intravenous and/or nasal drug abuse (within the past 6 months)

• Known allergy to MVA-BN vaccine or any of its constituents, e.g. tris (hydroxymethyl)-amino methane, including known 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/inactivated 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 (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 product within 30 days preceding the first dose of the trial vaccine, or planned administration of such a drug during the trial period

• Trial personnel

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Optimal Research, LLC (Synexus)	Melbourne	Florida	United States	32934
3	Optimal Research, LLC (Synexus)	Peoria	Illinois	United States	61614
4	University of Iowa	Iowa City	Iowa	United States	52242
5	University of Kentucky Healthcare Chandler Hospital	Lexington	Kentucky	United States	40536
6	Optimal Research, LLC (Synexus)	Rockville	Maryland	United States	20850
7	Saint Louis University	Saint Louis	Missouri	United States	63104
8	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
9	Rochester Clinical Research, Inc.	Rochester	New York	United States	14609
10	M3 Wake Research, Inc.	Raleigh	North Carolina	United States	27612
11	Lynn Health Science Institute	Oklahoma City	Oklahoma	United States	73112
12	Omega Medical Research	Warwick	Rhode Island	United States	02886

Sponsors and Collaborators

• Bavarian Nordic
• Biomedical Advanced Research and Development Authority

Investigators

• Principal Investigator: Edgar T Overton, MD, University of Alabama at Birmingham

Study Documents (Full-Text)

• Study Protocol - Nov 22, 2019
• Statistical Analysis Plan - Nov 22, 2019

More Information

Publications

None provided.

• Responsible Party: Bavarian Nordic
• ClinicalTrials.gov Identifier: NCT03699124
• Other Study ID Numbers: POX-MVA-031
• First Posted: Oct 9, 2018
• Last Update Posted: May 27, 2021
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Smallpox

Study Results

Participant Flow

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Period Title: Overall Study
STARTED	377	375	377
COMPLETED	332	335	337
NOT COMPLETED	45	40	40

Baseline Characteristics

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3	Total
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Total of all reporting groups
Overall Participants	377	375	377	1129
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	377 100%	375 100%	377 100%	1129 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.7 (7.31)	30.6 (7.29)	30.7 (7.50)	30.7 (7.36)
Sex: Female, Male (Count of Participants)
Female	210 55.7%	213 56.8%	207 54.9%	630 55.8%
Male	167 44.3%	162 43.2%	170 45.1%	499 44.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	28 7.4%	20 5.3%	25 6.6%	73 6.5%
Not Hispanic or Latino	348 92.3%	354 94.4%	349 92.6%	1051 93.1%
Unknown or Not Reported	1 0.3%	1 0.3%	3 0.8%	5 0.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.5%	2 0.5%	4 1.1%	8 0.7%
Asian	17 4.5%	13 3.5%	13 3.4%	43 3.8%
Native Hawaiian or Other Pacific Islander	1 0.3%	1 0.3%	0 0%	2 0.2%
Black or African American	58 15.4%	55 14.7%	59 15.6%	172 15.2%
White	292 77.5%	295 78.7%	293 77.7%	880 77.9%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	7 1.9%	9 2.4%	8 2.1%	24 2.1%
Region of Enrollment (participants) [Number]
United States	377 100%	375 100%	377 100%	1129 100%

Outcome Measures

1. Primary Outcome

Title	Vaccinia-Specific Neutralizing Antibodies Measured by Plaque Reduction Neutralization Test (PRNT)
Description	Vaccinia-specific neutralizing antibody titers below the lower limit of quantitation are given a value 10, i.e., half of the PRNT lower limit of quantitation of 20.
Time Frame	Two weeks post second vaccination; approximately Week 6.

Outcome Measure Data

Analysis Population Description

The Per Protocol Set includes all randomized subjects who received at least one vaccination and had no major protocol deviations that might have a substantial impact on the immunogenicity results.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	327	331	330
Geometric Mean (95% Confidence Interval) [Titer]	252.7	269.9	242.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GP 1: Two Doses of FD MVA-BN--Lot 1, GP 2: Two Doses of FD MVA-BN--Lot 2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence between two lot groups is demonstrated if the confidence interval of the ratio of the GMTs lies within the interval [½, 2]. For the trial to be successful, all three lot group comparisons must be equivalent by this definition.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.936
	Confidence Interval	(2-Sided) 95%; 0.816 to 1.073
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GP 2: Two Doses of FD MVA-BN--Lot 2, GP 3: Two Doses of FD MVA-BN--Lot 3
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence between two lot groups is demonstrated if the confidence interval of the ratio of the GMTs lies within the interval [½, 2]. For the trial to be successful, all three lot group comparisons must be equivalent by this definition.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.115
	Confidence Interval	(2-Sided) 95%; 0.967 to 1.287
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GP 1: Two Doses of FD MVA-BN--Lot 1, GP 3: Two Doses of FD MVA-BN--Lot 3
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence between two lot groups is demonstrated if the confidence interval of the ratio of the GMTs lies within the interval [½, 2]. For the trial to be successful, all three lot group comparisons must be equivalent by this definition.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.044
	Confidence Interval	(2-Sided) 95%; 0.915 to 1.191
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Vaccinia-Specific Total Antibodies Measured by Enzyme-Linked Immunosorbant Assay (ELISA)
Description	Vaccinia-specific total antibody titers below the lower limit of quantitation are given a value 100, i.e., half of the ELISA lower limit of quantitation of 200.
Time Frame	Two weeks post second vaccination; approximately Week 6.

Outcome Measure Data

Analysis Population Description

The Per Protocol Set includes all randomized subjects who received at least one vaccination and had no major protocol deviations that might have a substantial impact on the immunogenicity results.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	327	331	330
Geometric Mean (95% Confidence Interval) [Titer]	1222	1311	1226.1

3. Secondary Outcome

Title	Seroconversion Rates for Vaccinia-Specific Neutralizing Antibodies by PRNT
Description	Seroconversion is defined as either the appearance of antibody titers >= LLOQ for subjects with a titer below LLOQ at baseline, or a doubling (or more) of the antibody titer compared to the baseline titer for subjects with a titer equal or above the LLOQ at baseline. The LLOQ for PRNT is 20.
Time Frame	Two weeks post second vaccination; approximately Week 6.

Outcome Measure Data

Analysis Population Description

The Per Protocol Set includes all randomized subjects who received at least one vaccination and had no major protocol deviations that might have a substantial impact on the immunogenicity results. Only subjects who had both a baseline and two weeks post second vaccination titer results are included.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	326	331	330
Count of Participants [Participants]	325 86.2%	328 87.5%	327 86.7%

4. Secondary Outcome

Title	Seroconversion Rates for Vaccinia-Specific Total Antibodies by ELISA
Description	Seroconversion is defined as either the appearance of antibody titers >= LLOQ for subjects with a titer below LLOQ at baseline, or a doubling (or more) of the antibody titer compared to the baseline titer for subjects with a titer equal or above the LLOQ at baseline. The LLOQ for ELISA is 200.
Time Frame	Two weeks post second vaccination; approximately Week 6.

Outcome Measure Data

Analysis Population Description

The Per Protocol Set includes all randomized subjects who received at least one vaccination and had no major protocol deviations that might have a substantial impact on the immunogenicity results. Only subjects who had both a baseline and two weeks post second vaccination titer results are included.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	326	331	330
Count of Participants [Participants]	323 85.7%	325 86.7%	326 86.5%

5. Secondary Outcome

Title	Pearson Correlation Coefficient Between the log10 Transformed PRNT Titers and the log10 Transformed ELISA Titers
Description	Pearson correlation coefficient calculated on the log10 PRNT vs. ELISA titers at 2 weeks post second vaccination.
Time Frame	Two weeks post second vaccination; approximately Week 6.

Outcome Measure Data

Analysis Population Description

The Per Protocol Set includes all randomized subjects who received at least one vaccination and had no major protocol deviations that might have a substantial impact on the immunogenicity results.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	327	331	330
Number (95% Confidence Interval) [Correlation Coefficient]	0.657	0.657	0.656

6. Secondary Outcome

Title	Occurrence, Relationship and Intensity of Any Serious Adverse Event (SAE) at Any Time During the Trial
Description	Occurrence is defined as the number of participants who experienced an SAE. Related SAEs are defined as those for which causality to trial vaccine was considered possible, probable, definite, or was missing. Intensity is defined per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, published September 2007, where >= Grade 3 is either Severe or Potentially Life Threatening.
Time Frame	Overall study, ie from first vaccination at Visit 1 through the Follow-up Visit approximately 32 weeks post first vaccination.

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all subjects who were randomized and received at least one dose of trial vaccine, regardless of the occurrence of protocol deviations.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	377	375	377
Any Serious Adverse Event	1 0.3%	7 1.9%	1 0.3%
Related Serious Adverse Event	0 0%	0 0%	0 0%
Serious Adverse Event >= Grade 3	0 0%	5 1.3%	1 0.3%

7. Secondary Outcome

Title	Occurrence, Relationship and Intensity of Any Cardiac Sign or Symptom Indicating a Case of Myo-/Pericarditis at Any Time During the Trial.
Description	Occurrence is defined as the number of participants who experienced an event falling in the system organ class of "Cardiac disorders" per MedDRA version 22.0. Related cardiac signs and symptoms are defined as those for which causality to trial vaccine was considered possible, probable, definite, or was missing. Intensity is defined per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, published September 2007, where >= Grade 3 is either Severe or Potentially Life Threatening.
Time Frame	Overall study, ie from first vaccination at Visit 1 through the Follow-up Visit approximately 32 weeks post first vaccination.

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all subjects who were randomized and received at least one dose of trial vaccine, regardless of the occurrence of protocol deviations.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	377	375	377
Any Cardiac Sign or Symptom	1 0.3%	2 0.5%	1 0.3%
Any Related Cardiac Sign or Symptom	0 0%	0 0%	0 0%
Any Cardiac Sign or Symptom >=Grade 3	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Occurrence of Any Grade 3 or 4 Unsolicited AEs Probably, Possibly or Definitely Related to the Trial Vaccine
Description	Related AEs are defined as those for which causality to trial vaccine was considered possible, probable, definite, or was missing. Intensity is defined per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, published September 2007, where Grade 3 is Severe and Grade 4 is Potentially Life Threatening.
Time Frame	Within 28 days (and up to 35 days) after each vaccination, ie, from Visit 1 to Visit 3 for the first vaccination and from Visit 3 to Visit 5 for the second vaccination based on the protocol scheduled visits.

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all subjects who were randomized and received at least one dose of trial vaccine, regardless of the occurrence of protocol deviations.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	377	375	377
Count of Participants [Participants]	2 0.5%	0 0%	1 0.3%

9. Secondary Outcome

Title	Occurrence, Relationship and Intensity of Unsolicited AEs
Description	Occurrence is defined as the number of participants who experienced an unsolicited AE. Related unsolicited AEs are defined as those for which causality to trial vaccine was considered possible, probable, definite, or was missing. Intensity is defined per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, published September 2007, where >= Grade 3 is either Severe or Potentially Life Threatening.
Time Frame	Within 28 days (and up to 35 days) after each vaccination, ie, from Visit 1 to Visit 3 for the first vaccination and from Visit 3 to Visit 5 for the second vaccination based on the protocol scheduled visits.

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all subjects who were randomized and received at least one dose of trial vaccine, regardless of the occurrence of protocol deviations.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	377	375	377
Any Unsolicited AE	88 23.3%	110 29.3%	98 26%
Any Related Unsolicited AE	33 8.8%	38 10.1%	37 9.8%
Any Unsolicited AE >= Grade 3	6 1.6%	8 2.1%	7 1.9%

10. Secondary Outcome

Title	Occurrence and Intensity of Solicited Local AEs (Redness, Swelling, Induration, Pruritus and Pain).
Description	Occurrence is defined as the number of participants who experienced a solicited local AE. Intensity is defined per the protocol for each local event type. For injection site erythema, swelling, and induration the intensity is graded based on the maximum diameter as Grade 1: < 30mm, Grade 2: >= 30 - < 100mm, Grade 3: >= 100mm. Intensity for pruritis is defined as Grade 1: mild, Grade 2: moderate, Grade 3: severe. Intensity for injection site pain is defined as Grade 1: Painful on touch, Grade 2: Painful when moving the limb, Grade 3: Spontaneously painful/prevents normal activity. If a participant experienced the local event after both vaccinations, the maximum intensity is presented.
Time Frame	During the 8 day period (day of vaccination and the following 7 days) after each vaccination, ie Days 1-8 for the first vaccination and Days 28-35 for the second vaccination based on the protocol scheduled visits.

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all subjects who were randomized and received at least one dose of trial vaccine, regardless of the occurrence of protocol deviations.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	377	375	377
Any Solicited Local AEs	338 89.7%	348 92.8%	344 91.2%
Any Redness	271 71.9%	283 75.5%	272 72.1%
Redness Grade 1	84 22.3%	110 29.3%	87 23.1%
Redness Grade 2	143 37.9%	131 34.9%	156 41.4%
Redness Grade 3	44 11.7%	42 11.2%	29 7.7%
Any Swelling	215 57%	233 62.1%	236 62.6%
Swelling Grade 1	88 23.3%	121 32.3%	118 31.3%
Swelling Grade 2	110 29.2%	87 23.2%	106 28.1%
Swelling Grade 3	17 4.5%	25 6.7%	12 3.2%
Any Induration	215 57%	226 60.3%	229 60.7%
Induration Grade 1	98 26%	126 33.6%	123 32.6%
Induration Grade 2	106 28.1%	92 24.5%	100 26.5%
Induration Grade 3	11 2.9%	8 2.1%	6 1.6%
Any Pruritis	210 55.7%	230 61.3%	198 52.5%
Pruritis Grade 1	160 42.4%	181 48.3%	159 42.2%
Pruritis Grade 2	40 10.6%	42 11.2%	29 7.7%
Pruritis Grade 3	10 2.7%	7 1.9%	10 2.7%
Any Injection Site Pain	325 86.2%	330 88%	329 87.3%
Injection Site Pain Grade 1	118 31.3%	112 29.9%	124 32.9%
Injection Site Pain Grade 2	161 42.7%	173 46.1%	162 43%
Injection Site Pain Grade 3	46 12.2%	45 12%	43 11.4%

11. Secondary Outcome

Title	Duration of Solicited Local AEs (Redness, Swelling, Induration, Pruritus and Pain).
Description	Number of days from the start of the local event to resolution. If a participant experienced the local event after both vaccinations, the longer duration is presented. Subjects who had a missing resolution date for the event are not included in the analysis.
Time Frame	Starting during the 8 day period (day of vaccination and the following 7 days) after each vaccination, ie, Days 1-8 for the first vaccination and Days 28-35 for the second vaccination based on the protocol scheduled visits, through resolution.

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all subjects who were randomized and received at least one dose of trial vaccine, regardless of the occurrence of protocol deviations.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	377	375	377
Redness	7.1 (6.53)	6.5 (5.06)	6.6 (5.39)
Swelling	6.7 (6.47)	6 (5.04)	5.9 (4.52)
Induration	18 (24.04)	13.9 (13.12)	15 (15.01)
Pruritis	5 (5.7)	4.4 (3.24)	4.4 (3.87)
Pain	6.9 (4.41)	7.1 (4.44)	6.7 (3.64)

12. Secondary Outcome

Title	Occurrence, Relationship, and Intensity of Solicited General AEs (Pyrexia, Headache, Myalgia, Nausea, Fatigue and Chills).
Description	Occurrence is defined as the number of participants who experienced a solicited general AE. Related solicited general AEs are defined as those for which causality to trial vaccine was considered possible, probable, definite, or was missing. Intensity is defined per the protocol for each general event type. For pyrexia (increased body temperature) grading is defined as Grade 1: ≥ 99.5 - < 100.4°F (≥ 37.5 - < 38.0°C), Grade 2:≥ 100.4 - < 102.2°F (≥ 38.0 - < 39.0°C), Grade 3:≥ 102.2 - < 104°F (≥ 39.0 - < 40.0°C), and Grade 4: ≥ 104°F (≥ 40.0°C). Intensity for headache, myalgia, nausea, fatigue and chills is defined as Grade 1: mild, Grade 2: moderate, Grade 3: severe. If a participant experienced the general event after both vaccinations, the maximum intensity is presented.
Time Frame	During the 8 day period (day of vaccination and the following 7 days) after each vaccination, ie Days 1-8 for the first vaccination and Days 28-35 for the second vaccination based on the protocol scheduled visits.

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all subjects who were randomized and received at least one dose of trial vaccine, regardless of the occurrence of protocol deviations.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	377	375	377
Any Solicited General AEs	253 67.1%	267 71.2%	266 70.6%
Any Related Solicited General AEs	246 65.3%	256 68.3%	252 66.8%
Any Pyrexia	47 12.5%	60 16%	63 16.7%
Pyrexia Grade 1	39 10.3%	48 12.8%	49 13%
Pyrexia Grade 2	7 1.9%	8 2.1%	13 3.4%
Pyrexia Grade 3	1 0.3%	4 1.1%	1 0.3%
Pyrexia Grade 4	0 0%	0 0%	0 0%
Any Related Pyrexia	47 12.5%	57 15.2%	55 14.6%
Any Headache	146 38.7%	157 41.9%	155 41.1%
Headache Grade 1	96 25.5%	102 27.2%	120 31.8%
Headache Grade 2	36 9.5%	44 11.7%	25 6.6%
Headache Grade 3	14 3.7%	11 2.9%	10 2.7%
Any Related Headache	140 37.1%	145 38.7%	145 38.5%
Any Myalgia	166 44%	173 46.1%	175 46.4%
Myalgia Grade 1	115 30.5%	116 30.9%	116 30.8%
Myalgia Grade 2	38 10.1%	47 12.5%	39 10.3%
Myalgia Grade 3	13 3.4%	10 2.7%	20 5.3%
Any Related Myalgia	159 42.2%	167 44.5%	167 44.3%
Any Nausea	75 19.9%	81 21.6%	78 20.7%
Nausea Grade 1	53 14.1%	56 14.9%	54 14.3%
Nausea Grade 2	16 4.2%	19 5.1%	18 4.8%
Nausea Grade 3	6 1.6%	6 1.6%	6 1.6%
Any Related Nausea	73 19.4%	73 19.5%	67 17.8%
Any Fatigue	140 37.1%	171 45.6%	171 45.4%
Fatigue Grade 1	82 21.8%	111 29.6%	99 26.3%
Fatigue Grade 2	43 11.4%	47 12.5%	58 15.4%
Fatigue Grade 3	15 4%	13 3.5%	14 3.7%
Any Related Fatigue	135 35.8%	163 43.5%	161 42.7%
Any Chills	58 15.4%	54 14.4%	57 15.1%
Chills Grade 1	43 11.4%	28 7.5%	38 10.1%
Chills Grade 2	10 2.7%	22 5.9%	13 3.4%
Chills Grade 3	5 1.3%	4 1.1%	6 1.6%
Any Related Chills	55 14.6%	50 13.3%	53 14.1%

13. Secondary Outcome

Title	Duration of Solicited General AEs (Pyrexia [Body Temperature Increase], Headache, Myalgia, Nausea, Fatigue and Chills)
Description	Number of days from the start of the general event to resolution. If a participant experienced the general event after both vaccinations, the longer duration is presented. Subjects who had a missing resolution date for the event are not included in the analysis.
Time Frame	Starting during the 8 day period (day of vaccination and the following 7 days) after each vaccination, ie, Days 1-8 for the first vaccination and Days 28-35 for the second vaccination based on the protocol scheduled visits, through resolution.

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all subjects who were randomized and received at least one dose of trial vaccine, regardless of the occurrence of protocol deviations.

Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1	GP 2: Two Doses of FD MVA-BN--Lot 2	GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
Measure Participants	377	375	377
Pyrexia	2.3 (1.87)	1.9 (1.91)	1.9 (1.92)
Headache	3.2 (2.85)	3.1 (2.49)	3.2 (3.59)
Myalgia	4.1 (2.8)	4 (3.27)	4.1 (3.3)
Nausea	2.6 (2.98)	2.7 (2.76)	2.7 (2.5)
Fatigue	3.9 (5.16)	3.1 (2.7)	3.6 (3.57)
Chills	2.3 (2.01)	2.3 (2.71)	2.3 (2.19)

Adverse Events

Time Frame	Overall study, ie, from first vaccination at Visit 1 through the Follow-up Visit approximately 32 weeks post first vaccination.
Adverse Event Reporting Description	Non-systematic assessments include unsolicited adverse events collected at each visit. Systematic events include solicited adverse events collected in a memory aid for 8 days after the vaccinations at Visit 1 (Days 1-8) and Visit 3 (Days 28-35).
Arm/Group Title	GP 1: Two Doses of FD MVA-BN--Lot 1		GP 2: Two Doses of FD MVA-BN--Lot 2		GP 3: Two Doses of FD MVA-BN--Lot 3
Arm/Group Description	Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)		Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)		Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3 FD MVA-BN: Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)
All Cause Mortality
	GP 1: Two Doses of FD MVA-BN--Lot 1		GP 2: Two Doses of FD MVA-BN--Lot 2		GP 3: Two Doses of FD MVA-BN--Lot 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/377 (0%)		2/375 (0.5%)		0/377 (0%)
Serious Adverse Events
	GP 1: Two Doses of FD MVA-BN--Lot 1		GP 2: Two Doses of FD MVA-BN--Lot 2		GP 3: Two Doses of FD MVA-BN--Lot 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/377 (0.3%)		7/375 (1.9%)		1/377 (0.3%)
Gastrointestinal disorders
Alcoholic pancreatitis	0/377 (0%)	0	0/375 (0%)	0	1/377 (0.3%)	1
Colitis	0/377 (0%)	0	1/375 (0.3%)	1	0/377 (0%)	0
General disorders
Death	0/377 (0%)	0	2/375 (0.5%)	2	0/377 (0%)	0
Infections and infestations
Groin abscess	0/377 (0%)	0	1/375 (0.3%)	1	0/377 (0%)	0
Musculoskeletal and connective tissue disorders
Foot deformity	0/377 (0%)	0	1/375 (0.3%)	1	0/377 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/377 (0%)	0	1/375 (0.3%)	1	0/377 (0%)	0
Psychiatric disorders
Depression	1/377 (0.3%)	1	0/375 (0%)	0	0/377 (0%)	0
Panic attack	0/377 (0%)	0	1/375 (0.3%)	1	0/377 (0%)	0
Other (Not Including Serious) Adverse Events
	GP 1: Two Doses of FD MVA-BN--Lot 1		GP 2: Two Doses of FD MVA-BN--Lot 2		GP 3: Two Doses of FD MVA-BN--Lot 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	347/377 (92%)		353/375 (94.1%)		349/377 (92.6%)
Gastrointestinal disorders
Nausea	75/377 (19.9%)	90	81/375 (21.6%)	104	78/377 (20.7%)	96
General disorders
Chills	58/377 (15.4%)	65	54/375 (14.4%)	62	57/377 (15.1%)	63
Fatigue	140/377 (37.1%)	186	171/375 (45.6%)	225	171/377 (45.4%)	235
Injection site erythema	271/377 (71.9%)	439	283/375 (75.5%)	465	272/377 (72.1%)	459
Injection site induration	215/377 (57%)	328	226/375 (60.3%)	355	229/377 (60.7%)	346
Injection site pain	325/377 (86.2%)	573	330/375 (88%)	581	329/377 (87.3%)	576
Injection site pruritis	210/377 (55.7%)	303	230/375 (61.3%)	338	198/377 (52.5%)	284
Injection site swelling	215/377 (57%)	324	233/375 (62.1%)	343	236/377 (62.6%)	360
Pyrexia	47/377 (12.5%)	56	60/375 (16%)	75	63/377 (16.7%)	72
Infections and infestations
Upper respiratory tract infection	19/377 (5%)	19	25/375 (6.7%)	26	21/377 (5.6%)	23
Musculoskeletal and connective tissue disorders
Myalgia	166/377 (44%)	225	173/375 (46.1%)	238	175/377 (46.4%)	241
Nervous system disorders
Headache	146/377 (38.7%)	189	157/375 (41.9%)	208	155/377 (41.1%)	208

Limitations/Caveats

There were no limitations on the trial.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The agreement entitles Bavarian Nordic to request the Institution(s) to delay their publication for a period of up to six (6) months from the date of the first submission to Bavarian Nordic.