Trial Outcomes & Findings for A Non-inferiority Trial to Compare MVA-BN® Smallpox Vaccine to ACAM2000® (NCT NCT01913353)
NCT ID: NCT01913353
Last Updated: 2019-12-05
Results Overview
GMT based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of 1.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
440 participants
Primary outcome timeframe
Day 42 for Group 1 and Day 28 for Group 2
Results posted on
2019-12-05
Participant Flow
Participant milestones
| Measure |
Group 1
Two vaccinations; MVA BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA BN® vaccination (Day 56).
MVA BN®: 0.5 ml MVA BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
|---|---|---|
|
Overall Study
STARTED
|
221
|
219
|
|
Overall Study
COMPLETED
|
189
|
204
|
|
Overall Study
NOT COMPLETED
|
32
|
15
|
Reasons for withdrawal
| Measure |
Group 1
Two vaccinations; MVA BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA BN® vaccination (Day 56).
MVA BN®: 0.5 ml MVA BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
0
|
|
Overall Study
Physician Decision
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
20
|
6
|
|
Overall Study
multiple reasons
|
10
|
7
|
Baseline Characteristics
A Non-inferiority Trial to Compare MVA-BN® Smallpox Vaccine to ACAM2000®
Baseline characteristics by cohort
| Measure |
Group 1
n=220 Participants
Two vaccinations; MVA BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA BN® vaccination (Day 56).
MVA BN®: 0.5 ml MVA BN® with a nominal titre of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=213 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Total
n=433 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
23.5 years
STANDARD_DEVIATION 4.77 • n=5 Participants
|
23.4 years
STANDARD_DEVIATION 4.58 • n=7 Participants
|
23.5 years
STANDARD_DEVIATION 4.67 • n=5 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
68 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
181 Participants
n=5 Participants
|
184 Participants
n=7 Participants
|
365 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
54 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
166 Participants
n=5 Participants
|
173 Participants
n=7 Participants
|
339 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
14 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
48 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
126 Participants
n=5 Participants
|
136 Participants
n=7 Participants
|
262 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
19 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Region of Enrollment
South Korea
|
220 participants
n=5 Participants
|
213 participants
n=7 Participants
|
433 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 42 for Group 1 and Day 28 for Group 2Population: Per-protocol Set for Immunogenicity
GMT based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of 1.
Outcome measures
| Measure |
Group 1
n=185 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=186 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT) at the Peak Visits
|
153.5 Titer
Interval 134.3 to 175.6
|
79.3 Titer
Interval 67.1 to 93.8
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 6-8, 13-15 after 3rd Vaccination for Group 1 and Day 6-8, 13-15 after 1st vaccination for Group 2Population: Per-protocol Set
The MLA was defined as the maximum of two measurements: the lesion area measured on Day 6-8 (after scarification) or the lesion area measured on Day 13-15 (after scarification). This was measured using the SilhouetteConnect camera system, and confirmed by the Independent Take Review Committee (ITRC).
Outcome measures
| Measure |
Group 1
n=165 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=161 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
Maximum Lesion Area (MLA) in mm2 After Scarification With ACAM2000®
|
0.0 mm2
Interval 0.0 to 2.0
|
76.0 mm2
Interval 70.0 to 87.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 6-8 and Day 13-15 after ACAM2000 scarificationPopulation: Per-protocol Set
The MLD was defined as the largest major diameter measured across the lesion on Day 6-8 (after scarification) or Day 13-15 (after scarification)
Outcome measures
| Measure |
Group 1
n=165 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=161 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
Investigator-measured Maximum Lesion Diameter (MLD) in mm After Scarification With ACAM2000
|
0.0 mm
Interval 0.0 to 2.0
|
11.0 mm
Interval 10.0 to 11.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 6-8 after ACAM2000 scarificationPopulation: Per-protocol Set
The lesion diameter at Day 6-8 was defined as the major lesion diameter measured on Day 6-8 (after scarification)
Outcome measures
| Measure |
Group 1
n=165 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=161 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
Investigator-measured Lesion Diameter in mm at Day 6-8 After Scarification With ACAM2000
|
0.0 mm
Interval 0.0 to 2.0
|
8.0 mm
Interval 8.0 to 9.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 13-15 after ACAM2000 scarificationPopulation: Per-protocol Set
The lesion diameter at Day 13-15 was defined as the major lesion diameter measured on Day 13-15 (after scarification)
Outcome measures
| Measure |
Group 1
n=165 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=161 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
Investigator-measured Lesion Diameter in mm at Day 13-15 After Scarification With ACAM2000
|
0.0 mm
Interval 0.0 to 0.0
|
10.0 mm
Interval 10.0 to 11.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 6-8 visit following ACAM2000 vaccinationPopulation: Per-protocol Set
Take was assessed as either full, partial, or absent take by the ITRC based on Day 6-8 evaluations following ACAM2000 vaccination using subject profiles that contained supportive data up to Day 14 following ACAM2000 vaccination (in accordance with the ITRC Charter).
Outcome measures
| Measure |
Group 1
n=165 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=161 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC)
Full Take
|
23.0 percentage of subjects
Interval 16.8 to 30.2
|
92.5 percentage of subjects
Interval 87.3 to 96.1
|
—
|
—
|
|
Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC)
Partial Take
|
23.0 percentage of subjects
Interval 16.8 to 30.2
|
4.3 percentage of subjects
Interval 1.8 to 8.8
|
—
|
—
|
|
Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC)
Absent Take
|
53.9 percentage of subjects
Interval 46.0 to 61.7
|
1.9 percentage of subjects
Interval 0.4 to 5.3
|
—
|
—
|
|
Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC)
Missing
|
0 percentage of subjects
Interval 0.0 to 2.2
|
1.2 percentage of subjects
Interval 0.2 to 4.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 6-8 after ACAM2000 scarificationPopulation: Per-protocol Set
Lesion area was measured by the Investigator using the SilhouetteConnect camera system and confirmed by the blinded ITRC.
Outcome measures
| Measure |
Group 1
n=165 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=161 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
Lesion Area in mm2 at Day 6-8 After Scarification With ACAM2000
|
0.0 mm2
Interval 0.0 to 1.0
|
37.0 mm2
Interval 33.0 to 42.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 13-15 after ACAM2000 scarificationPopulation: Per-protocol Set
Lesion area was measured by the Investigator using the SilhouetteConnect camera system and confirmed by the blinded ITRC.
Outcome measures
| Measure |
Group 1
n=165 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=161 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
Lesion Area in mm2 at Day 13-15 After Scarification With ACAM2000
|
0.0 mm2
Interval 0.0 to 0.0
|
75.0 mm2
Interval 69.0 to 85.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Within 38 weeks for Group 1 and 30 weeks for Group 2Population: Full Analysis Set
Presentation of SAEs by relationship to study vaccine
Outcome measures
| Measure |
Group 1
n=220 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=213 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
Relationship to Vaccine of Any Serious Adverse Event (SAE)
Unrelated/None
|
4 Events
|
2 Events
|
—
|
—
|
|
Relationship to Vaccine of Any Serious Adverse Event (SAE)
Unlikely
|
1 Events
|
1 Events
|
—
|
—
|
|
Relationship to Vaccine of Any Serious Adverse Event (SAE)
Possible
|
0 Events
|
0 Events
|
—
|
—
|
|
Relationship to Vaccine of Any Serious Adverse Event (SAE)
Probable
|
0 Events
|
0 Events
|
—
|
—
|
|
Relationship to Vaccine of Any Serious Adverse Event (SAE)
Definite
|
0 Events
|
0 Events
|
—
|
—
|
SECONDARY outcome
Timeframe: Within 38 weeks for Group 1 and 30 weeks for Group 2Population: Full Analysis Set
Presentation of SAEs by intensity
Outcome measures
| Measure |
Group 1
n=220 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=213 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
Intensity of Any Serious Adverse Event (SAE)
Mild: routine daily activity not impaired
|
0 participants
|
0 participants
|
—
|
—
|
|
Intensity of Any Serious Adverse Event (SAE)
Moderate: routine daily activity impaired
|
0 participants
|
0 participants
|
—
|
—
|
|
Intensity of Any Serious Adverse Event (SAE)
Severe: prevents routine daily activities
|
1 participants
|
1 participants
|
—
|
—
|
|
Intensity of Any Serious Adverse Event (SAE)
Life threatening
|
4 participants
|
2 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Within 38 weeks for Group 1 and 30 weeks for Group 2Population: Full Analysis Set
In this clinical trial, an AESI was defined as any cardiac sign or symptom developed since the first vaccination, any ECG changes determined to be clinically significant, or any cardiac enzyme results of Troponin I ≥ 2 x ULN.
Outcome measures
| Measure |
Group 1
n=220 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=208 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
n=196 Participants
after ACAM2000
|
Group 2
n=213 Participants
ACAM2000
|
|---|---|---|---|---|
|
Incidence of Any Cardiac Sign or Symptom Indicating a Case of Myo-/Pericarditis, i.e. Adverse Events of Special Interest (AESIs)
|
2 Participants
|
2 Participants
|
3 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: within 29 days after vaccinationPopulation: Full Analysis Set
Incidence of any Grade 3 or 4 adverse events (AEs) possibly, probably, or definitely related to the vaccine. Pooled solicited (general only) and unsolicited AEs.
Outcome measures
| Measure |
Group 1
n=220 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=208 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
n=196 Participants
after ACAM2000
|
Group 2
n=213 Participants
ACAM2000
|
|---|---|---|---|---|
|
Related Grade >=3 Adverse Events
|
3 Participants
|
2 Participants
|
3 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: within 29 days after vaccinationPopulation: Full Analysis Set
Presentation of non-serious AEs by relationship to study vaccine
Outcome measures
| Measure |
Group 1
n=220 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=208 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
n=196 Participants
after ACAM2000
|
Group 2
n=213 Participants
ACAM2000
|
|---|---|---|---|---|
|
Relationship to Vaccine of Any Non-serious AEs
Unrelated/None
|
94 Events
|
67 Events
|
110 Events
|
102 Events
|
|
Relationship to Vaccine of Any Non-serious AEs
Unlikely
|
24 Events
|
19 Events
|
29 Events
|
23 Events
|
|
Relationship to Vaccine of Any Non-serious AEs
Possible
|
27 Events
|
15 Events
|
18 Events
|
30 Events
|
|
Relationship to Vaccine of Any Non-serious AEs
Probable
|
5 Events
|
1 Events
|
0 Events
|
6 Events
|
|
Relationship to Vaccine of Any Non-serious AEs
Definite
|
107 Events
|
56 Events
|
9 Events
|
34 Events
|
SECONDARY outcome
Timeframe: within 29 days after vaccinationPopulation: Full Analysis Set
Presentation of non-serious AEs by intensity
Outcome measures
| Measure |
Group 1
n=220 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=208 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
n=196 Participants
after ACAM2000
|
Group 2
n=213 Participants
ACAM2000
|
|---|---|---|---|---|
|
Intensity of Any Non-serious AEs
Mild
|
233 Events
|
141 Events
|
143 Events
|
163 Events
|
|
Intensity of Any Non-serious AEs
Moderate
|
20 Events
|
16 Events
|
18 Events
|
25 Events
|
|
Intensity of Any Non-serious AEs
Severe
|
4 Events
|
1 Events
|
5 Events
|
7 Events
|
SECONDARY outcome
Timeframe: within 15 days after vaccinationPopulation: Full Analysis Set
Occurrence, intensity and relationship of solicited general AEs (body temperature \[fever\], headache, myalgia \[muscle pain\], chills, nausea, fatigue, malaise)
Outcome measures
| Measure |
Group 1
n=208 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=193 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
n=187 Participants
after ACAM2000
|
Group 2
n=200 Participants
ACAM2000
|
|---|---|---|---|---|
|
Solicited General AEs
Pyrexia, Grade 1, Related
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Solicited General AEs
Pyrexia, Grade 2, Related
|
2 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Solicited General AEs
Pyrexia, Grade 3, Related
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Solicited General AEs
Headache, Grade 1, Related
|
25 Participants
|
11 Participants
|
17 Participants
|
38 Participants
|
|
Solicited General AEs
Headache, Grade 2, Related
|
6 Participants
|
3 Participants
|
7 Participants
|
21 Participants
|
|
Solicited General AEs
Headache, Grade 3, Related
|
1 Participants
|
2 Participants
|
1 Participants
|
9 Participants
|
|
Solicited General AEs
Myalgia, Grade 1, Related
|
28 Participants
|
13 Participants
|
15 Participants
|
44 Participants
|
|
Solicited General AEs
Myalgia, Grade 2, Related
|
5 Participants
|
5 Participants
|
2 Participants
|
21 Participants
|
|
Solicited General AEs
Myalgia, Grade 3, Related
|
0 Participants
|
1 Participants
|
0 Participants
|
7 Participants
|
|
Solicited General AEs
Chills, Grade 1, Related
|
1 Participants
|
0 Participants
|
8 Participants
|
19 Participants
|
|
Solicited General AEs
Chills, Grade 2, Related
|
0 Participants
|
2 Participants
|
2 Participants
|
12 Participants
|
|
Solicited General AEs
Chills, Grade 3, Related
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Solicited General AEs
Nausea, Grade 1, Related
|
7 Participants
|
4 Participants
|
6 Participants
|
21 Participants
|
|
Solicited General AEs
Nausea, Grade 2, Related
|
0 Participants
|
2 Participants
|
4 Participants
|
12 Participants
|
|
Solicited General AEs
Nausea, Grade 3, Related
|
1 Participants
|
0 Participants
|
1 Participants
|
6 Participants
|
|
Solicited General AEs
Fatigue, Grade 1, Related
|
29 Participants
|
14 Participants
|
21 Participants
|
45 Participants
|
|
Solicited General AEs
Fatigue, Grade 2, Related
|
7 Participants
|
2 Participants
|
7 Participants
|
30 Participants
|
|
Solicited General AEs
Fatigue, Grade 3, Related
|
1 Participants
|
1 Participants
|
1 Participants
|
8 Participants
|
|
Solicited General AEs
Malaise, Grade 1, Related
|
16 Participants
|
6 Participants
|
12 Participants
|
30 Participants
|
|
Solicited General AEs
Malaise, Grade 2, Related
|
5 Participants
|
2 Participants
|
8 Participants
|
25 Participants
|
|
Solicited General AEs
Malaise, Grade 3, Related
|
2 Participants
|
1 Participants
|
2 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: within 29 days after vaccinationPopulation: Full Analysis Set
Incidence of events of Lymphadenopathy. Pooled solicited and unsolicited events.
Outcome measures
| Measure |
Group 1
n=220 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=208 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
n=196 Participants
after ACAM2000
|
Group 2
n=213 Participants
ACAM2000
|
|---|---|---|---|---|
|
Incidence of Lymphadenopathy
|
24 Participants
|
15 Participants
|
17 Participants
|
109 Participants
|
SECONDARY outcome
Timeframe: within 15 days after vaccinationPopulation: Full Analysis Set
Incidence of solicited local AEs (pain, redness \[erythema\], swelling, induration, itching \[pruritus\])
Outcome measures
| Measure |
Group 1
n=208 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=193 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
n=187 Participants
after ACAM2000
|
Group 2
n=200 Participants
ACAM2000
|
|---|---|---|---|---|
|
Solicited Local AEs: Intensity
Injection Site Induration, Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Pain, Grade 1
|
72 Participants
|
49 Participants
|
21 Participants
|
58 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Pain, Grade 2
|
21 Participants
|
22 Participants
|
6 Participants
|
44 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Pain, Grade 3
|
4 Participants
|
0 Participants
|
1 Participants
|
33 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Erythema, Grade 1
|
44 Participants
|
40 Participants
|
106 Participants
|
105 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Erythema, Grade 2
|
9 Participants
|
10 Participants
|
9 Participants
|
81 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Erythema, Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
5 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Swelling, Grade 1
|
14 Participants
|
16 Participants
|
46 Participants
|
120 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Swelling, Grade 2
|
5 Participants
|
6 Participants
|
0 Participants
|
17 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Swelling, Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Induration, Grade 1
|
23 Participants
|
11 Participants
|
44 Participants
|
125 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Induration, Grade 2
|
1 Participants
|
2 Participants
|
1 Participants
|
7 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Pruritus, Grade 1
|
24 Participants
|
19 Participants
|
99 Participants
|
101 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Pruritus, Grade 2
|
3 Participants
|
1 Participants
|
11 Participants
|
60 Participants
|
|
Solicited Local AEs: Intensity
Injection Site Pruritus, Grade 3
|
2 Participants
|
0 Participants
|
1 Participants
|
18 Participants
|
SECONDARY outcome
Timeframe: Within 15 days after scarification with ACAM2000Population: Full Analysis Set
Daily measurement of major lesion size, major erythema, and major induration diameter (mm) based on physical appearance of vaccination site as documented in the memory aid. If the shape of the lesion, erythema \[excludes lymphangitis\], and induration observed was not round but rather asymmetrical, then the largest \[or major\] cross-sectional measurement was recorded.
Outcome measures
| Measure |
Group 1
n=220 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=213 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
Major Lesion Size, Major Erythema, and Major Induration Diameter
Maximum Lesion Diameter
|
5.0 mm
Interval 4.0 to 5.0
|
11.5 mm
Interval 11.0 to 12.0
|
—
|
—
|
|
Major Lesion Size, Major Erythema, and Major Induration Diameter
Maximum Erythema
|
6.0 mm
Interval 5.0 to 7.0
|
26.0 mm
Interval 25.0 to 30.0
|
—
|
—
|
|
Major Lesion Size, Major Erythema, and Major Induration Diameter
Maximum Induration
|
5.0 mm
Interval 4.0 to 9.0
|
15.0 mm
Interval 13.0 to 16.0
|
—
|
—
|
SECONDARY outcome
Timeframe: within 8 weeks (for both groups)Population: Per-protocol Set for Immunogenicity
Peak Visit was defined as Day 42 for Group 1 and Day 28 for Group 2. Individual Peak was the maximum titer per subject from Visit 1 to Visit 7 (Week 8) in Group 1 and maximum titer from Visit 1 to Visit 6 (Week 8) in Group 2. Titers below the detection limit are included with a value of 1.
Outcome measures
| Measure |
Group 1
n=185 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=186 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
GMTs at the Peak Visits and Individual Peak Measured by Vaccinia-specific ELISA
Peak Visit
|
1076.9 Titer
Interval 956.8 to 1212.0
|
194.6 Titer
Interval 162.6 to 232.9
|
—
|
—
|
|
GMTs at the Peak Visits and Individual Peak Measured by Vaccinia-specific ELISA
Individual Peak
|
1105.2 Titer
Interval 983.4 to 1242.0
|
214.0 Titer
Interval 177.8 to 257.6
|
—
|
—
|
SECONDARY outcome
Timeframe: within 8 weeks (for both groups)Population: Per-protocol Set for Immunogenicity
Individual Peak was the maximum titer per subject from Visit 1 to Visit 7 (Week 8) in Group 1 and maximum titer from Visit 1 to Visit 6 (Week 8) in Group 2. Titers below the detection limit are included with a value of 1.
Outcome measures
| Measure |
Group 1
n=185 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=186 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
GMTs at the Individual Peak Measured by Vaccinia-specific PRNT
|
201.5 Titer
Interval 178.5 to 227.5
|
117.8 Titer
Interval 102.3 to 135.7
|
—
|
—
|
SECONDARY outcome
Timeframe: within 12 weeksPopulation: Per-protocol Set for Immunogenicity
GMT based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.
Outcome measures
| Measure |
Group 1
n=185 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=186 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
GMTs as Measured by Vaccinia-specific ELISA
Week 0
|
1.2 Titer
Interval 1.1 to 1.3
|
1.2 Titer
Interval 1.0 to 1.3
|
—
|
—
|
|
GMTs as Measured by Vaccinia-specific ELISA
Week 1
|
1.6 Titer
Interval 1.3 to 2.0
|
1.2 Titer
Interval 1.0 to 1.3
|
—
|
—
|
|
GMTs as Measured by Vaccinia-specific ELISA
Week 2
|
104.9 Titer
Interval 84.0 to 131.0
|
21.9 Titer
Interval 15.9 to 30.2
|
—
|
—
|
|
GMTs as Measured by Vaccinia-specific ELISA
Week 4
|
129.8 Titer
Interval 107.1 to 157.2
|
194.6 Titer
Interval 162.6 to 232.9
|
—
|
—
|
|
GMTs as Measured by Vaccinia-specific ELISA
Week 6
|
1076.9 Titer
Interval 956.8 to 1212.0
|
149.2 Titer
Interval 123.6 to 180.1
|
—
|
—
|
|
GMTs as Measured by Vaccinia-specific ELISA
Week 8
|
671.9 Titer
Interval 597.2 to 755.8
|
113.7 Titer
Interval 93.2 to 138.7
|
—
|
—
|
|
GMTs as Measured by Vaccinia-specific ELISA
Week 12
|
550.5 Titer
Interval 482.2 to 628.4
|
NA Titer
No week 12 visit for Group 2
|
—
|
—
|
SECONDARY outcome
Timeframe: within 12 weeksPopulation: Per-protocol Set for Immunogenicity
GMT based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.
Outcome measures
| Measure |
Group 1
n=185 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=186 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
GMTs as Measured by Vaccinia-specific PRNT
Week 0
|
1.0 Titer
Interval 1.0 to 1.1
|
1.0 Titer
Interval 1.0 to 1.0
|
—
|
—
|
|
GMTs as Measured by Vaccinia-specific PRNT
Week 1
|
1.1 Titer
Interval 1.0 to 1.3
|
1.0 Titer
Interval 1.0 to 1.0
|
—
|
—
|
|
GMTs as Measured by Vaccinia-specific PRNT
Week 2
|
16.2 Titer
Interval 13.0 to 20.1
|
16.2 Titer
Interval 13.1 to 20.0
|
—
|
—
|
|
GMTs as Measured by Vaccinia-specific PRNT
Week 4
|
16.9 Titer
Interval 13.7 to 20.8
|
79.3 Titer
Interval 67.1 to 93.8
|
—
|
—
|
|
GMTs as Measured by Vaccinia-specific PRNT
Week 6
|
153.5 Titer
Interval 134.3 to 175.6
|
64.7 Titer
Interval 54.9 to 76.2
|
—
|
—
|
|
GMTs as Measured by Vaccinia-specific PRNT
Week 8
|
118.2 Titer
Interval 102.9 to 135.8
|
67.1 Titer
Interval 56.9 to 79.0
|
—
|
—
|
|
GMTs as Measured by Vaccinia-specific PRNT
Week 12
|
96.5 Titer
Interval 80.1 to 116.2
|
NA Titer
No week 12 visit for Group 2
|
—
|
—
|
SECONDARY outcome
Timeframe: Group 1 at Week 6; Group 2 at Week 4Population: Per-protocol Set for Immunogenicity
Seroconversion rate based on PRNT. Seroconversion is defined as the appearance of antibody titers "greater than or equal" 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.
Outcome measures
| Measure |
Group 1
n=185 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=186 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
PRNT Seroconversion Rates at Peak Visits
|
100.0 percentage of subjects
Interval 98.0 to 100.0
|
97.3 percentage of subjects
Interval 93.8 to 99.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Group 1 at Week 6; Group 2 at Week 4Population: Per-protocol Set for Immunogenicity
Seroconversion rate based on ELISA. Seroconversion is defined as the appearance of antibody titers "greater than or equal" 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.
Outcome measures
| Measure |
Group 1
n=185 Participants
Two vaccinations; MVA-BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA-BN® vaccination (Day 56).
MVA-BN®: 0.5 ml MVA-BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 2
n=186 Participants
A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
|
Group 1, Period 3
after ACAM2000
|
Group 2
ACAM2000
|
|---|---|---|---|---|
|
ELISA Seroconversion Rates at Peak Visits
|
100 percentage of subjects
Interval 98.0 to 100.0
|
96.8 percentage of subjects
Interval 93.1 to 98.8
|
—
|
—
|
Adverse Events
Group 1, Period 1
Serious events: 2 serious events
Other events: 95 other events
Deaths: 0 deaths
Group 1, Period 2
Serious events: 0 serious events
Other events: 63 other events
Deaths: 0 deaths
Group 1, Period 3
Serious events: 3 serious events
Other events: 79 other events
Deaths: 0 deaths
Group 2
Serious events: 3 serious events
Other events: 88 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group 1, Period 1
n=220 participants at risk
after 1st dose of MVA-BN
|
Group 1, Period 2
n=208 participants at risk
after 2nd dose of MVA-BN
|
Group 1, Period 3
n=196 participants at risk
after ACAM2000
|
Group 2
n=213 participants at risk
ACAM2000
|
|---|---|---|---|---|
|
Infections and infestations
Appendicitis
|
0.45%
1/220 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/208 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/196 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/213 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Psychiatric disorders
Suicidal Ideation
|
0.00%
0/220 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/208 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.51%
1/196 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/213 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Injury, poisoning and procedural complications
Alcohol Poisoning
|
0.00%
0/220 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/208 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.51%
1/196 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/213 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Infections and infestations
Peritonsillar Abscess
|
0.00%
0/220 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/208 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.51%
1/196 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/213 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Injury, poisoning and procedural complications
Road Traffic Accident
|
0.00%
0/220 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/208 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/196 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.47%
1/213 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/220 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/208 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/196 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.47%
1/213 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/220 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/208 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/196 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.47%
1/213 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Injury, poisoning and procedural complications
Tibia Fracture
|
0.45%
1/220 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/208 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/196 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/213 • 38 weeks for Group 1 and 30 weeks for Group 2
|
Other adverse events
| Measure |
Group 1, Period 1
n=220 participants at risk
after 1st dose of MVA-BN
|
Group 1, Period 2
n=208 participants at risk
after 2nd dose of MVA-BN
|
Group 1, Period 3
n=196 participants at risk
after ACAM2000
|
Group 2
n=213 participants at risk
ACAM2000
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
4.5%
10/220 • Number of events 11 • 38 weeks for Group 1 and 30 weeks for Group 2
|
2.9%
6/208 • Number of events 6 • 38 weeks for Group 1 and 30 weeks for Group 2
|
1.5%
3/196 • Number of events 3 • 38 weeks for Group 1 and 30 weeks for Group 2
|
10.8%
23/213 • Number of events 27 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
General disorders
Axillary Pain
|
0.00%
0/220 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/208 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/196 • 38 weeks for Group 1 and 30 weeks for Group 2
|
2.3%
5/213 • Number of events 5 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
General disorders
Injection Site Erythema
|
13.6%
30/220 • Number of events 30 • 38 weeks for Group 1 and 30 weeks for Group 2
|
11.1%
23/208 • Number of events 23 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.51%
1/196 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/213 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
General disorders
Injection Site Nodule
|
14.5%
32/220 • Number of events 38 • 38 weeks for Group 1 and 30 weeks for Group 2
|
6.2%
13/208 • Number of events 13 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.51%
1/196 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/213 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
General disorders
Vaccination Site Erythema
|
4.5%
10/220 • Number of events 10 • 38 weeks for Group 1 and 30 weeks for Group 2
|
3.4%
7/208 • Number of events 7 • 38 weeks for Group 1 and 30 weeks for Group 2
|
1.0%
2/196 • Number of events 2 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/213 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
General disorders
Vaccination Site Nodule
|
5.0%
11/220 • Number of events 11 • 38 weeks for Group 1 and 30 weeks for Group 2
|
1.4%
3/208 • Number of events 3 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/196 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.94%
2/213 • Number of events 2 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
General disorders
Vaccination Site Warmth
|
5.9%
13/220 • Number of events 13 • 38 weeks for Group 1 and 30 weeks for Group 2
|
4.8%
10/208 • Number of events 10 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.51%
1/196 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/213 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Infections and infestations
Nasopharyngitis
|
3.2%
7/220 • Number of events 7 • 38 weeks for Group 1 and 30 weeks for Group 2
|
1.9%
4/208 • Number of events 4 • 38 weeks for Group 1 and 30 weeks for Group 2
|
3.1%
6/196 • Number of events 6 • 38 weeks for Group 1 and 30 weeks for Group 2
|
2.3%
5/213 • Number of events 5 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
6.4%
14/220 • Number of events 14 • 38 weeks for Group 1 and 30 weeks for Group 2
|
6.7%
14/208 • Number of events 14 • 38 weeks for Group 1 and 30 weeks for Group 2
|
7.1%
14/196 • Number of events 14 • 38 weeks for Group 1 and 30 weeks for Group 2
|
6.6%
14/213 • Number of events 14 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Injury, poisoning and procedural complications
Laceration
|
2.3%
5/220 • Number of events 5 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.48%
1/208 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
2.0%
4/196 • Number of events 4 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.47%
1/213 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.8%
4/220 • Number of events 5 • 38 weeks for Group 1 and 30 weeks for Group 2
|
1.9%
4/208 • Number of events 4 • 38 weeks for Group 1 and 30 weeks for Group 2
|
1.0%
2/196 • Number of events 2 • 38 weeks for Group 1 and 30 weeks for Group 2
|
2.8%
6/213 • Number of events 6 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
3.2%
7/220 • Number of events 7 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/208 • 38 weeks for Group 1 and 30 weeks for Group 2
|
2.0%
4/196 • Number of events 4 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.47%
1/213 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Nervous system disorders
Headache
|
1.8%
4/220 • Number of events 4 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.96%
2/208 • Number of events 2 • 38 weeks for Group 1 and 30 weeks for Group 2
|
3.1%
6/196 • Number of events 6 • 38 weeks for Group 1 and 30 weeks for Group 2
|
2.3%
5/213 • Number of events 5 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/220 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/208 • 38 weeks for Group 1 and 30 weeks for Group 2
|
2.0%
4/196 • Number of events 4 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.47%
1/213 • Number of events 1 • 38 weeks for Group 1 and 30 weeks for Group 2
|
|
Skin and subcutaneous tissue disorders
Dermatitis Contact
|
0.00%
0/220 • 38 weeks for Group 1 and 30 weeks for Group 2
|
0.00%
0/208 • 38 weeks for Group 1 and 30 weeks for Group 2
|
22.4%
44/196 • Number of events 44 • 38 weeks for Group 1 and 30 weeks for Group 2
|
23.0%
49/213 • Number of events 49 • 38 weeks for Group 1 and 30 weeks for Group 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place