Trial Outcomes & Findings for A Randomized, Double-blind, Placebo-controlled Study on Immunogenicity and Safety of MVA-BN (IMVAMUNE™) Smallpox Vaccine in Healthy Subjects (NCT NCT00316524)
NCT ID: NCT00316524
Last Updated: 2019-03-06
Results Overview
Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
745 participants
Primary outcome timeframe
2 weeks following the last vaccination (Week 6 for Groups 1-3, Week 2 for Group 4)
Results posted on
2019-03-06
Participant Flow
Participant milestones
| Measure |
Group 1: 2 x MVA-BN® s.c., Vaccinia Naive
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5mL MVA-BN® IMVAMUNE (1x10E08 TCID50)
|
Group 2: 1x MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5mL MVA-BN® IMVAMUNE (1x10E08 TCID50), followed by one vaccination Placebo (0.5mL Tris Buffer)
|
Group 3: Two x Placebo, s.c., Vaccinia Naive
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5mL Tris Buffer).
Placebo: Tris-Buffer
|
Group 4: 1x MVA-BN®, s.c., Vaccinia Experienced
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID50).
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
183
|
181
|
181
|
200
|
|
Overall Study
COMPLETED
|
175
|
173
|
175
|
200
|
|
Overall Study
NOT COMPLETED
|
8
|
8
|
6
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Randomized, Double-blind, Placebo-controlled Study on Immunogenicity and Safety of MVA-BN (IMVAMUNE™) Smallpox Vaccine in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Group 1: 2x MVA-BN® s.c., Vaccinia Naive
n=183 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5mL MVA-BN® IMVAMUNE (1x10E08 TCID50)
|
Group 2: 1x MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=181 Participants
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5mL MVA-BN® IMVAMUNE (1x10E08 TCID50), followed by one vaccination Placebo (0.5mL Tris Buffer)
|
Group 3: 2x Placebo, s.c., Vaccinia Naive
n=181 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5mL Tris Buffer)
Placebo: Tris-Buffer
|
Group 4: 1x MVA-BN®, s.c., Vaccinia Experienced
n=200 Participants
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5mL MVA-BN® IMVAMUNE (1x10E08 TCID50)
|
Total
n=745 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
25.3 years
STANDARD_DEVIATION 4.98 • n=5 Participants
|
25.4 years
STANDARD_DEVIATION 4.38 • n=7 Participants
|
26.0 years
STANDARD_DEVIATION 5.1 • n=5 Participants
|
41.5 years
STANDARD_DEVIATION 7.59 • n=4 Participants
|
29.8 years
STANDARD_DEVIATION 9.07 • n=21 Participants
|
|
Sex: Female, Male
Female
|
97 Participants
n=5 Participants
|
112 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
115 Participants
n=4 Participants
|
431 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
86 Participants
n=5 Participants
|
69 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
85 Participants
n=4 Participants
|
314 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Ethnic group · Caucasian
|
178 Participants
n=5 Participants
|
176 Participants
n=7 Participants
|
177 Participants
n=5 Participants
|
198 Participants
n=4 Participants
|
729 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Ethnic group · Asian
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Ethnic group · Black
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Ethnic group · Arabic
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Ethnic group · Other
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Region of Enrollment
Germany
|
183 participants
n=5 Participants
|
181 participants
n=7 Participants
|
181 participants
n=5 Participants
|
200 participants
n=4 Participants
|
745 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 2 weeks following the last vaccination (Week 6 for Groups 1-3, Week 2 for Group 4)Population: Full Analysis Set
Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Outcome measures
| Measure |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=176 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=174 Participants
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID), followed by one subcutaneous vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=175 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer)
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=200 Participants
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Percentage of Participants With Seroconversion by ELISA
|
98.9 percentage of subjects
Interval 96.0 to 99.9
|
82.2 percentage of subjects
Interval 75.7 to 87.6
|
3.4 percentage of subjects
Interval 1.3 to 7.3
|
95.5 percentage of subjects
Interval 91.6 to 97.9
|
PRIMARY outcome
Timeframe: within 2 weeks after each vaccinationPopulation: Safety dataset
Occurrence of any specific or unspecific ECG change. Assessments at Screening (SCR), Visit 2 (Week 2) and Visit 4 (Week 6).
Outcome measures
| Measure |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=183 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=181 Participants
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID), followed by one subcutaneous vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=181 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer)
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=200 Participants
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Number of Participants With ECG Changes
SCR : Supraventricular arrhytmia
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Changes
SCR : Ventricular arrhythmia
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Changes
SCR : AV block (PQ time >0.20 sec) 1st degree
|
0 participants
|
0 participants
|
1 participants
|
1 participants
|
|
Number of Participants With ECG Changes
SCR : Right bundle branch block - incomplete
|
10 participants
|
18 participants
|
4 participants
|
1 participants
|
|
Number of Participants With ECG Changes
SCR : ST elevation
|
5 participants
|
1 participants
|
4 participants
|
1 participants
|
|
Number of Participants With ECG Changes
SCR : ST depression
|
0 participants
|
1 participants
|
0 participants
|
1 participants
|
|
Number of Participants With ECG Changes
SCR : T inversion - pathological
|
42 participants
|
54 participants
|
50 participants
|
48 participants
|
|
Number of Participants With ECG Changes
SCR : T inversion - other
|
14 participants
|
19 participants
|
22 participants
|
16 participants
|
|
Number of Participants With ECG Changes
SCR : Low voltage
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With ECG Changes
SCR : Other non-specific changes
|
23 participants
|
23 participants
|
26 participants
|
5 participants
|
|
Number of Participants With ECG Changes
SCR : Bradycardia
|
30 participants
|
28 participants
|
30 participants
|
6 participants
|
|
Number of Participants With ECG Changes
SCR : Arrhythmia
|
4 participants
|
3 participants
|
8 participants
|
1 participants
|
|
Number of Participants With ECG Changes
SCR : Repolarisation
|
3 participants
|
3 participants
|
3 participants
|
0 participants
|
|
Number of Participants With ECG Changes
SCR : Q-Abnormalities
|
1 participants
|
1 participants
|
0 participants
|
4 participants
|
|
Number of Participants With ECG Changes
SCR : Tall T-waves
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Changes
Week 2 : Supraventricular arrhytmia
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Changes
Week 2 : Ventricular arrhythmia
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With ECG Changes
Week 2 : AV block (PQ time >0.20 sec) 1st degree
|
0 participants
|
0 participants
|
1 participants
|
1 participants
|
|
Number of Participants With ECG Changes
Week 2 : Right bundle branch block - incomplete
|
9 participants
|
17 participants
|
15 participants
|
15 participants
|
|
Number of Participants With ECG Changes
Week 2 : ST elevation
|
3 participants
|
1 participants
|
2 participants
|
0 participants
|
|
Number of Participants With ECG Changes
Week 2 : ST depression
|
0 participants
|
1 participants
|
1 participants
|
1 participants
|
|
Number of Participants With ECG Changes
Week 2 : T inversion - pathological
|
34 participants
|
46 participants
|
40 participants
|
31 participants
|
|
Number of Participants With ECG Changes
Week 2 : T inversion - other
|
11 participants
|
9 participants
|
10 participants
|
7 participants
|
|
Number of Participants With ECG Changes
Week 2 : Low voltage
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Changes
Week 2 : Other non-specific changes
|
34 participants
|
29 participants
|
34 participants
|
14 participants
|
|
Number of Participants With ECG Changes
Week 2 : Bradycardia
|
31 participants
|
25 participants
|
33 participants
|
6 participants
|
|
Number of Participants With ECG Changes
Week 2 : Arrhythmia
|
4 participants
|
4 participants
|
2 participants
|
5 participants
|
|
Number of Participants With ECG Changes
Week 2 : Repolarisation
|
1 participants
|
3 participants
|
2 participants
|
1 participants
|
|
Number of Participants With ECG Changes
Week 2 : Q-Abnormalities
|
0 participants
|
3 participants
|
1 participants
|
4 participants
|
|
Number of Participants With ECG Changes
Week 2 : Tall T-waves
|
1 participants
|
3 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Changes
Week 6 : Supraventricular arrhytmia
|
1 participants
|
1 participants
|
0 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : Ventricular arrhythmia
|
0 participants
|
0 participants
|
0 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : AV block (PQ time >0.20 sec) 1st degree
|
2 participants
|
0 participants
|
1 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : Right bundle branch block - incomplete
|
10 participants
|
20 participants
|
12 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : ST elevation
|
1 participants
|
3 participants
|
1 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : ST depression
|
1 participants
|
0 participants
|
0 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : T inversion - pathological
|
28 participants
|
37 participants
|
39 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : T inversion - other
|
3 participants
|
5 participants
|
4 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : Low voltage
|
0 participants
|
0 participants
|
0 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : Other non-specific changes
|
35 participants
|
35 participants
|
33 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : Bradycardia
|
30 participants
|
23 participants
|
28 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : Arrhythmia
|
4 participants
|
4 participants
|
2 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : Repolarisation
|
2 participants
|
3 participants
|
7 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : Q-Abnormalities
|
1 participants
|
0 participants
|
1 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
|
Number of Participants With ECG Changes
Week 6 : Tall T-waves
|
1 participants
|
1 participants
|
2 participants
|
NA participants
Visit not applicable to Group 4 subjects
|
PRIMARY outcome
Timeframe: within 32 weeksPopulation: Safety dataset
Occurrence and relationship of any other cardiac symptom at any time during the study
Outcome measures
| Measure |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=183 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=181 Participants
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID), followed by one subcutaneous vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=181 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer)
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=200 Participants
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])
Sinus tachycardia : related
|
0 events
|
0 events
|
0 events
|
0 events
|
|
Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])
Sinus tachycardia : unrelated
|
1 events
|
1 events
|
0 events
|
0 events
|
|
Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])
Tachycardia : related
|
0 events
|
1 events
|
0 events
|
1 events
|
|
Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])
Tachycardia : unrelated
|
1 events
|
0 events
|
0 events
|
1 events
|
|
Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])
Palpitations : related
|
0 events
|
1 events
|
0 events
|
2 events
|
|
Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])
Palpitations : unrelated
|
1 events
|
1 events
|
1 events
|
3 events
|
|
Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])
Mild pericardial effusion : related
|
0 events
|
0 events
|
0 events
|
0 events
|
|
Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])
Mild pericardial effusion : unrelated
|
0 events
|
0 events
|
0 events
|
1 events
|
SECONDARY outcome
Timeframe: 4 weeks following the last vaccination (Week 8 for Groups 1-3, Week 4 for Group 4)Population: Full Analysis Set (includes subjects with data available 4 weeks following the last vaccination)
Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Outcome measures
| Measure |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=178 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=175 Participants
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID), followed by one subcutaneous vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=177 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer)
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=199 Participants
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Percentage of Participants With Seroconversion by ELISA
|
98.9 percentage of subjects
|
72.0 percentage of subjects
|
2.8 percentage of subjects
|
93.0 percentage of subjects
|
SECONDARY outcome
Timeframe: 2 weeks following the last vaccination (Week 6 for Groups 1-3, Week 2 for Group 4)Population: Full Analysis Set
Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (6) 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 |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=176 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=174 Participants
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID), followed by one subcutaneous vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=175 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer)
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=200 Participants
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Percentage of Participants With Seroconversion by PRNT
|
89.2 percentage of subjects
|
56.3 percentage of subjects
|
0.0 percentage of subjects
|
78.5 percentage of subjects
|
SECONDARY outcome
Timeframe: 4 weeks following the last vaccination (Week 8 for Groups 1-3, Week 4 for Group 4)Population: Full Analysis Set (includes subjects with data available 4 weeks following the last vaccination)
Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (6) 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 |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=178 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=175 Participants
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID), followed by one subcutaneous vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=177 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer)
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=199 Participants
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Percentage of Participants With Seroconversion by PRNT
|
86.0 percentage of subjects
|
47.4 percentage of subjects
|
0.0 percentage of subjects
|
69.8 percentage of subjects
|
SECONDARY outcome
Timeframe: within 32 weeksPopulation: Safety dataset
Number of participants with any serious adverse event possibly, probably or definitely related to the study vaccine at any time during the study
Outcome measures
| Measure |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=183 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=181 Participants
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID), followed by one subcutaneous vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=181 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer)
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=200 Participants
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Number of Participants With Related Serious Adverse Events
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: within 8 days after any vaccinationPopulation: Safety dataset
Number of participants with solicited local AEs (pain, erythema, swelling and induration) within 8 days after any vaccination (vaccinations for Groups 1-3: Days 0 and 28; Group 4: Day 0). Percentages based on subjects with at least one completed diary card.
Outcome measures
| Measure |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=182 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=179 Participants
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID), followed by one subcutaneous vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=179 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer)
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=200 Participants
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Number of Participants With Solicited Local Adverse Events
Injection site pain
|
166 Participants
|
155 Participants
|
37 Participants
|
167 Participants
|
|
Number of Participants With Solicited Local Adverse Events
Injection site erythema
|
166 Participants
|
146 Participants
|
39 Participants
|
169 Participants
|
|
Number of Participants With Solicited Local Adverse Events
Injection site swelling
|
149 Participants
|
103 Participants
|
10 Participants
|
149 Participants
|
|
Number of Participants With Solicited Local Adverse Events
Injection site induration
|
162 Participants
|
146 Participants
|
5 Participants
|
155 Participants
|
SECONDARY outcome
Timeframe: within 8 days after any vaccinationPopulation: Safety dataset
Number of participants with solicited systemic/general AEs (body temperature increased, headache, myalgia, nausea, and fatigue) within 8 days after any vaccination (vaccinations for Groups 1-3: Days 0 and 28; Group 4: Day 0). Percentages based on subjects with at least one completed diary card.
Outcome measures
| Measure |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=182 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=179 Participants
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID), followed by one subcutaneous vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=179 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer)
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=200 Participants
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Number of Participants With Solicited General Adverse Events
Body temperature increased
|
18 Participants
|
21 Participants
|
10 Participants
|
10 Participants
|
|
Number of Participants With Solicited General Adverse Events
Headache
|
60 Participants
|
84 Participants
|
49 Participants
|
53 Participants
|
|
Number of Participants With Solicited General Adverse Events
Myalgia
|
29 Participants
|
22 Participants
|
20 Participants
|
42 Participants
|
|
Number of Participants With Solicited General Adverse Events
Nausea
|
17 Participants
|
22 Participants
|
13 Participants
|
18 Participants
|
|
Number of Participants With Solicited General Adverse Events
Fatigue
|
68 Participants
|
59 Participants
|
55 Participants
|
78 Participants
|
SECONDARY outcome
Timeframe: within 4 weeks after any vaccinationPopulation: Safety dataset
Number of participants with any Grade \>=3 AE probably, possibly, or definitely related to the study vaccine within 4 weeks after any vaccination (vaccinations for Groups 1-3: Days 0 and 28; Group 4: Day 0). Pooled solicited (local and general) and unsolicited AEs.
Outcome measures
| Measure |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=183 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=181 Participants
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID), followed by one subcutaneous vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=181 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer)
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=200 Participants
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Number of Participants With Related Grade>=3 Adverse Events
|
10 Participants
|
5 Participants
|
5 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: within 4 weeks after any vaccinationPopulation: Safety dataset
Number of participants with non-serious unsolicited AEs within 4 weeks after any vaccination (vaccinations for Groups 1-3: Days 0 and 28; Group 4: Day 0).
Outcome measures
| Measure |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=183 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=181 Participants
vaccinia naive subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID), followed by one subcutaneous vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=181 Participants
vaccinia naive subjects receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer)
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=200 Participants
vaccinia experienced subjects receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Number of Participants With Unsolicited Non-serious Adverse Events
|
113 Participants
|
106 Participants
|
78 Participants
|
99 Participants
|
Adverse Events
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
Serious events: 3 serious events
Other events: 91 other events
Deaths: 0 deaths
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
Serious events: 3 serious events
Other events: 88 other events
Deaths: 0 deaths
GP 3: Two x Placebo, s.c., Vaccinia Naive
Serious events: 5 serious events
Other events: 54 other events
Deaths: 0 deaths
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
Serious events: 1 serious events
Other events: 73 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=183 participants at risk
vaccinia naive subjects receiving two subcutanenous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=181 participants at risk
vaccinica naive subjects receiving one vaccination with 0.5ml MVA-BN® IMVAMUNE(1x10E08 TCID), followed by one vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=181 participants at risk
vaccinia naive subjects, receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer).
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=200 participants at risk
vaccinia experienced subjects, receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID).
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Immune system disorders
Sarcoidosis
|
0.55%
1/183 • Number of events 1 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Infections and infestations
Gastroenteritis salmonella
|
0.00%
0/183 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/183 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Injury, poisoning and procedural complications
Tendon injury
|
0.00%
0/183 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/183 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.50%
1/200 • Number of events 1 • 32 weeks
|
|
Endocrine disorders
Thyroid cyst
|
0.00%
0/183 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of thyroid gland
|
0.00%
0/183 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/183 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/183 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.00%
0/183 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Psychiatric disorders
Depression
|
0.00%
0/183 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Psychiatric disorders
Mental disorder
|
0.55%
1/183 • Number of events 1 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Surgical and medical procedures
Thyroidectomy
|
0.00%
0/183 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Surgical and medical procedures
Tonsillectomy
|
0.55%
1/183 • Number of events 1 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
Other adverse events
| Measure |
GP 1: Two x 1x10E08 TCID, MVA-BN® s.c., Vaccinia Naive
n=183 participants at risk
vaccinia naive subjects receiving two subcutanenous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., Vaccinia Naive
n=181 participants at risk
vaccinica naive subjects receiving one vaccination with 0.5ml MVA-BN® IMVAMUNE(1x10E08 TCID), followed by one vaccination Placebo (0.5ml Tris Buffer)
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
Placebo: Tris-Buffer
|
GP 3: Two x Placebo, s.c., Vaccinia Naive
n=181 participants at risk
vaccinia naive subjects, receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer).
Placebo: Tris-Buffer
|
GP 4: 1x10E08 TCID, MVA-BN®, s.c., Vaccinia Experienced
n=200 participants at risk
vaccinia experienced subjects, receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID).
MVA-BN® (IMVAMUNE): 1x 10E8\_TCID50
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
5.5%
10/183 • Number of events 11 • 32 weeks
|
8.8%
16/181 • Number of events 17 • 32 weeks
|
6.1%
11/181 • Number of events 11 • 32 weeks
|
3.0%
6/200 • Number of events 6 • 32 weeks
|
|
General disorders
Injection site pruritus
|
23.5%
43/183 • Number of events 61 • 32 weeks
|
19.9%
36/181 • Number of events 37 • 32 weeks
|
2.2%
4/181 • Number of events 4 • 32 weeks
|
24.5%
49/200 • Number of events 49 • 32 weeks
|
|
General disorders
Injection site hematoma
|
3.3%
6/183 • Number of events 6 • 32 weeks
|
5.0%
9/181 • Number of events 9 • 32 weeks
|
2.8%
5/181 • Number of events 5 • 32 weeks
|
2.0%
4/200 • Number of events 4 • 32 weeks
|
|
General disorders
Injection site warmth
|
4.9%
9/183 • Number of events 10 • 32 weeks
|
2.8%
5/181 • Number of events 5 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
4.0%
8/200 • Number of events 8 • 32 weeks
|
|
General disorders
Injection site discoloration
|
0.55%
1/183 • Number of events 1 • 32 weeks
|
2.2%
4/181 • Number of events 4 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Nervous system disorders
Dizziness
|
1.1%
2/183 • Number of events 3 • 32 weeks
|
3.9%
7/181 • Number of events 7 • 32 weeks
|
1.1%
2/181 • Number of events 3 • 32 weeks
|
2.0%
4/200 • Number of events 4 • 32 weeks
|
|
Blood and lymphatic system disorders
Lymphadenopaty
|
2.2%
4/183 • Number of events 5 • 32 weeks
|
2.2%
4/181 • Number of events 4 • 32 weeks
|
1.1%
2/181 • Number of events 2 • 32 weeks
|
2.0%
4/200 • Number of events 4 • 32 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.55%
1/183 • Number of events 1 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
2.2%
4/181 • Number of events 4 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
1.6%
3/183 • Number of events 3 • 32 weeks
|
2.2%
4/181 • Number of events 4 • 32 weeks
|
1.7%
3/181 • Number of events 3 • 32 weeks
|
3.0%
6/200 • Number of events 6 • 32 weeks
|
|
Infections and infestations
Bronchitis
|
1.6%
3/183 • Number of events 3 • 32 weeks
|
2.2%
4/181 • Number of events 4 • 32 weeks
|
1.1%
2/181 • Number of events 2 • 32 weeks
|
0.50%
1/200 • Number of events 1 • 32 weeks
|
|
Infections and infestations
Nasopharyngitis
|
23.0%
42/183 • Number of events 45 • 32 weeks
|
11.0%
20/181 • Number of events 20 • 32 weeks
|
14.4%
26/181 • Number of events 28 • 32 weeks
|
2.0%
4/200 • Number of events 4 • 32 weeks
|
|
Infections and infestations
Rhinitis
|
1.6%
3/183 • Number of events 3 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
2.2%
4/181 • Number of events 4 • 32 weeks
|
0.50%
1/200 • Number of events 1 • 32 weeks
|
|
Infections and infestations
Tonsilitis
|
2.2%
4/183 • Number of events 4 • 32 weeks
|
2.8%
5/181 • Number of events 5 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.2%
4/183 • Number of events 4 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
2.8%
5/181 • Number of events 5 • 32 weeks
|
1.0%
2/200 • Number of events 2 • 32 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.7%
5/183 • Number of events 5 • 32 weeks
|
0.55%
1/181 • Number of events 1 • 32 weeks
|
1.7%
3/181 • Number of events 3 • 32 weeks
|
0.00%
0/200 • 32 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
6.0%
11/183 • Number of events 11 • 32 weeks
|
5.0%
9/181 • Number of events 9 • 32 weeks
|
4.4%
8/181 • Number of events 9 • 32 weeks
|
2.0%
4/200 • Number of events 4 • 32 weeks
|
|
Vascular disorders
Hot flush
|
0.00%
0/183 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
0.00%
0/181 • 32 weeks
|
2.0%
4/200 • Number of events 4 • 32 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place