Randomized, Open-label Phase II Trial to Assess the Safet... | NCT02038881

Label	Type	Description	Intervention Names
Group 1 (standard regimen)	Experimental	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®)	Biological: IMVAMUNE®
Group 2 (double dose regimen)	Experimental	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®)	Biological: IMVAMUNE®
Group 3 (booster regimen)	Experimental	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®)	Biological: IMVAMUNE®

Name	Type	Description	Arm Group Labels	Other Names
IMVAMUNE®	Biological	0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml	Group 1 (standard regimen)

Measure	Description	Time Frame
Number of Participants With SAEs	Occurrence, relationship and intensity of any serious AE (SAE)	within 75 weeks

Measure	Description	Time Frame
Number of Participants With AESIs	Occurrence, relationship to the trial vaccine, and intensity of any adverse event of special interest (AESI)	within 75 weeks
Number of Participants With Related Grade >=3 Adverse Events

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male and female subjects aged between 18-45 years, vaccinia-naïve.
HIV-1 infection documented by ELISA and confirmed by Western blot at any time prior to study entry. HIV-1 deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), HIV-1 culture, HIV-1 antigen, plasma HIV-1 ribonucleic acid (RNA), or a second antibody test other than ELISA is acceptable as an alternative test at any time prior to study entry.
On stable antiretroviral therapy (ART) i.e. Combination ART for at least 6 months. Subject must be on the same ART regimen for at least 12 weeks with no change prior to enrollment in this clinical trial.
Screening HIV-1 RNA < 200 copies/ml by US Food and Drug Administration (FDA) approved PCR assay within 45 days prior to study entry.
Current CD4 counts ≥ 100 cells/µl ≤ 500 cells/µl.
Documented nadir CD4 count < 200 cells/µl at any time prior to enrollment.
Hemoglobin ≥ 9.0 g/dl for female subjects, ≥ 10.0 g/dl or male subjects.
Platelets ≥ 100,000/mm3.
Ability and willingness of subject to provide written informed consent.
Body Mass Index (BMI) ≥ 18.5 and < 35 kg/m2.
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 (SCR) and a negative urine pregnancy test within 24 hours prior to each vaccination.
Absolute neutrophil count cells ≥ 750/mm3.
Adequate renal function defined as a calculated Creatinine Clearance (CrCl) > 60 ml/min as estimated by the Cockcroft-Gault equation.
1. For men: (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dl x 72) = CrCl (ml/min)
2. For women: multiply the result by 0.85 = CrCl (ml/min).Adequate hepatic function defined as: Total bilirubin ≤ 2 x upper limit normal (ULN) in the absence of other evidence of significant liver disease
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 2.5 x ULN.
Troponin I < 2 x ULN at entry in the clinical trial.
Electrocardiogram (ECG) without clinically significant findings (e.g. any kind of atrioventricular or intraventricular conditions or blocks such as complete left or right bundle branch block, AV node block, QTc or PR prolongation, premature atrial contractions or other atrial arrhythmia, sustained ventricular arrhythmia, two premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia).

Exclusion Criteria:

Pregnant or breast-feeding women.
Typical vaccinia scar.
Known or suspected history of smallpox vaccination.
History of vaccination with any poxvirus-based vaccine.
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 including uncontrolled diabetes as according to the 'Division of Acquired Immune Deficiency Syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events' Version 1.0, December 2004, Clarification August 2009.
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 except those defined in the inclusion criteria, including, but not limited to clinically significant liver disease, diabetes mellitus type I and 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 (except HIV infection, chronic or active Hepatitis-B-Virus or Hepatitis-C-Virus infection).
Clinically significant psychiatric 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.
Current alcohol abuse (40 g/day for at least 6 month) and/or intravenous and/or intranasal 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 of enrollment.
Body temperature ≥ 100.4°F (≥ 38.0°C) at the time of enrollment.
Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior 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.
Use of immunosuppressant or immunomodulatory agents including systemic glucocorticoids (excluding nasal or inhaled steroids), tacrolimus, sirolimus, rapamycin, mycophenolate, cyclosporine, TNF-alpha blockers or antagonists, azathioprine, interferon, growth factors, or intravenous immunoglobulin in the 60 days prior to enrollment in this clinical trial.
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.
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
Edgar T Overton, MD	University of Alabama at Birmingham	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35294	United States
Health for Life Clinic Little Rock

PubMed Identifier	Type	Citation	Retractions
32057574	Derived	Overton ET, Lawrence SJ, Stapleton JT, Weidenthaler H, Schmidt D, Koenen B, Silbernagl G, Nopora K, Chaplin P. A randomized phase II trial to compare safety and immunogenicity of the MVA-BN smallpox vaccine at various doses in adults with a history of AIDS. Vaccine. 2020 Mar 4;38(11):2600-2607. doi: 10.1016/j.vaccine.2020.01.058. Epub 2020 Feb 11.

ID	Title	Description
FG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
FG001	Group 2 (Double Dose Regimen)

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 18, 2014	Jan 22, 2020

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

Number of Participants With SAEs

Occurrence, relationship and intensity of any serious AE (SAE)

Full Analysis Set

Posted

Count of Participants

Participants

within 75 weeks

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Units	Counts
Participants	OG00027 OG00129 OG00231

Title

Denominators

Categories

Any SAE

Title	Measurements
	OG0000 OG0010 OG0022

Any SAE with intensity >= Grade 3

Secondary

Number of Participants With AESIs

Occurrence, relationship to the trial vaccine, and intensity of any adverse event of special interest (AESI)

Full Analysis Set

Posted

Count of Participants

Participants

within 75 weeks

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

Number of Participants With Related Grade >=3 Adverse Events

Number of Participants with any Grade >=3 Adverse Event probably, possibly, or definitely related to the study vaccine. Pooled solicited and unsolicited AEs.

Full Analysis Set

Posted

Count of Participants

Participants

within 29 days after any vaccination

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

Number of Unsolicited Non-serious Adverse Events: 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 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

Number of Unsolicited Non-serious Adverse Events: 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 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

Number of Participants With Solicited Local Adverse Events

Number of participants with solicited local AEs (redness, swelling, induration, pruritus, and pain) by intensity. Percentages based on subjects with at least one completed diary card. [Injection site erythema, injection site swelling and injection site induration--all sizes measured in diameter with max severity of: 0=0, 1 = <30 mm, 2 = ≥30 - <100 mm, 3 = ≥100 mm. Injection site pruritus: 0=absent, 1=mild, 2=moderate, 3=severe. Injection site pain: 0=absent, 1=painful to touch, 2=painful when limb is moved, 3=spontaneously painful/prevents normal activity.]

Full Analysis Set

Posted

Count of Participants

Participants

within 8 days after any vaccination

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)

Secondary

Number of Participants With Solicited General AEs

Number of Participants with solicited systemic/general AEs (pyrexia, headache, myalgia, nausea, fatigue, and chills) by intensity. Percentages based on subjects with at least one completed diary card. [Body temperature: 0 = <99.5 F (<37.5 C), 1 = ≥99.5 - <100.4 F (≥37.5 - <38.0 C), 2= ≥100.4 - <102.2 F (≥38.0 - <39.0 C), 3= ≥102.2 - <104.0 F (≥39.0 - <40.0 C), 4= ≥ 104.0 F (≥40.0 C); pyrexia is defined as oral temperature ≥ 100.4 F (≥ 38.0 C).] [Headache, myalgia, nausea, chills and fatigue: 0 = none, 1 = mild: easily tolerated, minimal discomfort and no interference with daily activity, 2 = moderate: some interference with daily activity, 3 = severe: prevents daily activity.]

Full Analysis Set

Posted

Count of Participants

Participants

within 8 days after any vaccination

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

CD4+ T Cell Counts

Mean CD4+ T-cell counts over time

Full Analysis Set

Posted

Mean

Standard Deviation

CD4 count (cells/µL)

within 15 days after each vaccination

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Units

Secondary

Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points

GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.

Per-protocol Set

Posted

Geometric Mean

95% Confidence Interval

Titer

within 64 weeks

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

ELISA GMT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined))

GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.

Per-protocol Set

Posted

Geometric Mean

95% Confidence Interval

Titer

Week 6

ID	Title	Description
OG000	Group 1 and 3 Combined	Pooling of Groups 1 and 3 (same dose/regimen before booster vaccination in Group 3)
OG001	Group 2	Double dose regimen

Units	Counts
Participants	OG000

Secondary

ELISA GMT 2 Weeks Following the Last Vaccination

GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.

Per-protocol Set

Posted

Geometric Mean

95% Confidence Interval

Titer

Week 6 (Groups 1 and 2), Week 14 (Group 3)

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

ELISA GMT During Follow-up

GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'. Participants discontinued prior to the follow-up visits are excluded.

Per-protocol Set

Posted

Geometric Mean

95% Confidence Interval

Titer

Weeks 30 and 56 (Groups 1 and 2), Weeks 38 and 64 (Group 3)

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points

GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.

Per-protocol Set

Posted

Geometric Mean

95% Confidence Interval

Titer

within 64 weeks

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

PRNT GMT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined))

GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.

Per-protocol Set

Posted

Geometric Mean

95% Confidence Interval

Titer

Week 6

ID	Title	Description
OG000	Group 1 and 3 Combined	Pooling of Groups 1 and 3 (same dose/regimen before booster vaccination in Group 3)
OG001	Group 2	Double dose regimen

Units	Counts
Participants	OG000

Secondary

PRNT GMT 2 Weeks Following the Last Vaccination

GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.

Per-protocol Set

Posted

Geometric Mean

95% Confidence Interval

Titer

Week 6 (Groups 1 and 2), Week 14 (Group 3)

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

PRNT GMT During Follow-up

GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'. Participants discontinued prior to the follow-up visits are excluded.

Per-protocol Set

Posted

Geometric Mean

95% Confidence Interval

Titer

Weeks 30 and 56 (Groups 1 and 2), Weeks 38 and 64 (Group 3)

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

Percentage of Participants With Seroconversion by ELISA

SC rate based on ELISA. SC 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

within 64 weeks

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined))

Per-protocol Set

Posted

Number

95% Confidence Interval

percentage of subjects

Week 6

ID	Title	Description
OG000	Group 1 and 3 Combined	Pooling of Groups 1 and 3 (same dose/regimen before booster vaccination in Group 3)
OG001	Group 2	Double dose regimen

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Last Vaccination

Per-protocol Set

Posted

Number

95% Confidence Interval

percentage of subjects

Week 6 (Groups 1 and 2), Week 14 (Group 3)

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

Percentage of Participants With Seroconversion by ELISA During Follow-up

Per-protocol Set

Posted

Number

95% Confidence Interval

percentage of subjects

Weeks 30 and 56 (Groups 1 and 2), Weeks 38 and 64 (Group 3)

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

Percentage of Participants With Seroconversion by PRNT

SC rate based on PRNT. SC 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

within 64 weeks

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined))

Per-protocol Set

Posted

Number

95% Confidence Interval

percentage of subjects

Week 6

ID	Title	Description
OG000	Group 1 and 3 Combined	Pooling of Groups 1 and 3 (same dose/regimen before booster vaccination in Group 3)
OG001	Group 2	Double dose regimen

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Last Vaccination

Per-protocol Set

Posted

Number

95% Confidence Interval

percentage of subjects

Week 6 (Groups 1 and 2), Week 14 (Group 3)

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Secondary

Percentage of Participants With Seroconversion by PRNT During Follow-up

Per-protocol Set

Posted

Number

95% Confidence Interval

percentage of subjects

Weeks 30 and 56 (Groups 1 and 2), Weeks 38 and 64 (Group 3)

ID	Title	Description
OG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
OG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Inguinal hernia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Influenza like illness	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Non-cardiac chest pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected31 at risk
Furuncle	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected31 at risk
Herpes zoster	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected31 at risk
Influenza	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Rhinitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0011 events1 affected29 at risk EG0020 events0 affected31 at risk
Skin bacterial infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0011 events1 affected29 at risk EG0020 events0 affected31 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected31 at risk
Human bite	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Ulna fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Blood creatinine increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0011 events1 affected29 at risk EG0021 events1 affected31 at risk
Troponin I increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0011 events1 affected29 at risk EG0020 events0 affected31 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0011 events1 affected29 at risk EG0021 events1 affected31 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected31 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0011 events1 affected29 at risk EG0021 events1 affected31 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected31 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected27 at risk EG0011 events1 affected29 at risk EG0020 events0 affected31 at risk

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

ID	Title	Description
BG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
BG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
BG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group 1 (Standard Regimen)	One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml	27	0	27	5	27
EG001	Group 2 (Double Dose Regimen)	Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml	29	0	29	6	29
EG002	Group 3 (Booster Regimen)	One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml	31	2	31	10	31

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Pancreatitis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk
Depression	Psychiatric disorders	MedDRA 20.0	Systematic Assessment		EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected31 at risk