Trial Outcomes & Findings for A Phase II Trial to Compare a Liquid-frozen and a Freeze-dried Formulation of IMVAMUNE (MVA-BN®) Smallpox Vaccine in Vaccinia-naïve Healthy Subjects (NCT NCT01668537)
NCT ID: NCT01668537
Last Updated: 2020-10-12
Results Overview
Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Titers below the detection limit are included with a value of '1'
COMPLETED
PHASE2
651 participants
Week 6
2020-10-12
Participant Flow
Participant milestones
| Measure |
LF Formulation
Liquid Frozen (LF) formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, subcutaneous (s.c.), 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
Freeze Dried (FD) formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Overall Study
STARTED
|
327
|
324
|
|
Overall Study
COMPLETED
|
305
|
314
|
|
Overall Study
NOT COMPLETED
|
22
|
10
|
Reasons for withdrawal
| Measure |
LF Formulation
Liquid Frozen (LF) formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, subcutaneous (s.c.), 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
Freeze Dried (FD) formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Overall Study
Request to Discontinue Prematurely
|
1
|
1
|
|
Overall Study
Subject unwilling/unable to comply
|
5
|
0
|
|
Overall Study
Reason Precludes Participation
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
13
|
6
|
|
Overall Study
Other
|
2
|
3
|
Baseline Characteristics
A Phase II Trial to Compare a Liquid-frozen and a Freeze-dried Formulation of IMVAMUNE (MVA-BN®) Smallpox Vaccine in Vaccinia-naïve Healthy Subjects
Baseline characteristics by cohort
| Measure |
LF Formulation
n=327 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=324 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
Total
n=651 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
27.8 years
STANDARD_DEVIATION 6.36 • n=5 Participants
|
27.6 years
STANDARD_DEVIATION 6.21 • n=7 Participants
|
27.7 years
STANDARD_DEVIATION 6.28 • n=5 Participants
|
|
Sex: Female, Male
Female
|
178 Participants
n=5 Participants
|
170 Participants
n=7 Participants
|
348 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
149 Participants
n=5 Participants
|
154 Participants
n=7 Participants
|
303 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
95 Participants
n=5 Participants
|
95 Participants
n=7 Participants
|
190 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
232 Participants
n=5 Participants
|
229 Participants
n=7 Participants
|
461 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
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
78 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
145 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
239 Participants
n=5 Participants
|
247 Participants
n=7 Participants
|
486 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
327 participants
n=5 Participants
|
324 participants
n=7 Participants
|
651 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 6Population: Per Protocol Analysis Set
Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Titers below the detection limit are included with a value of '1'
Outcome measures
| Measure |
LF Formulation
n=297 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=306 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
ELISA GMT
|
875.1 Titer
Interval 801.3 to 955.7
|
1099.6 Titer
Interval 1014.8 to 1191.6
|
SECONDARY outcome
Timeframe: up to 32 weeksPopulation: Full Analysis Set
Occurrence, relationship to the trial vaccine and intensity of any Serious Adverse Event (SAE).
Outcome measures
| Measure |
LF Formulation
n=327 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=324 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Number of Participants With Serious Adverse Events
SAE
|
5 Participants
|
2 Participants
|
|
Number of Participants With Serious Adverse Events
SAE related to vaccine
|
0 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events
SAE Grade >=3
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: up to 32 weeksPopulation: Full Analysis Set
Occurrence, relationship to the trial vaccine and intensity of any Adverse Event of Special Interest (AESI). AESIs were defined as any cardiac symptoms and ECG changes determined to be clinically significant or cardiac enzyme troponin I elevated above 2 x the Upper Limit of Normal
Outcome measures
| Measure |
LF Formulation
n=327 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=324 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Number of Participants With Adverse Events of Special Interest (AESI)
AESI
|
1 Participants
|
4 Participants
|
|
Number of Participants With Adverse Events of Special Interest (AESI)
Drug-related AESI
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events of Special Interest (AESI)
AESI Grade >=3
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: within 29 days after vaccinationPopulation: Full Analysis Set
Occurrence of any Grade \>=3 Adverse Events related to the trial vaccine.
Outcome measures
| Measure |
LF Formulation
n=327 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=324 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Number of Participants With Related Grade >=3 Adverse Events
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: within 29 days after vaccinationPopulation: Full Analysis Set
Occurrence, relationship to the trial vaccine and intensity of unsolicited treatment-emergent AEs (TEAEs).
Outcome measures
| Measure |
LF Formulation
n=327 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=324 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Number of Participants With Unsolicited Adverse Events
TEAE
|
313 Participants
|
310 Participants
|
|
Number of Participants With Unsolicited Adverse Events
Drug-Related TEAE
|
207 Participants
|
207 Participants
|
|
Number of Participants With Unsolicited Adverse Events
TEAE Grade >=3
|
6 Participants
|
5 Participants
|
|
Number of Participants With Unsolicited Adverse Events
Drug-Related TEAE Grade >=3
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 8 days after any vaccinationPopulation: Subjects of the Full Analysis Set with at least one completed diary card
Occurrence and intensity of solicited local AEs (redness, swelling, induration, pruritus and pain) during the 8-day period (day of vaccination and the following 7 days) after any vaccination. Events were graded by intensity (1 = mild, 2 = moderate, 3 = severe).
Outcome measures
| Measure |
LF Formulation
n=322 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=321 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Number of Participants With Solicited Local Averse Events
Injection site pain : All
|
274 participants
|
290 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site pain : Grade >=2
|
138 participants
|
167 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site pain : Grade =3
|
22 participants
|
35 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site erythema : All
|
247 participants
|
255 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site erythema : Grade >=2
|
140 participants
|
181 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site erythema : Grade =3
|
16 participants
|
47 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site swelling : All
|
210 participants
|
223 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site swelling : Grade >=2
|
94 participants
|
125 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site swelling : Grade =3
|
10 participants
|
23 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site induration : All
|
211 participants
|
213 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site induration : Grade >=2
|
73 participants
|
96 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site induration : Grade =3
|
5 participants
|
6 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site pruritus : All
|
177 participants
|
189 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site pruritus : Grade >=2
|
38 participants
|
47 participants
|
|
Number of Participants With Solicited Local Averse Events
Injection site pruritus : Grade =3
|
7 participants
|
11 participants
|
SECONDARY outcome
Timeframe: within 8 days after any vaccinationPopulation: Subjects of the Full Analysis Set with at least one completed diary card
Occurrence, intensity and relationship to the trial vaccines of solicited general AEs (pyrexia, headache, myalgia, nausea, fatigue and chills) during the 8-day period (day of vaccination and the following 7 days) after any vaccination. Events were graded by intensity (1 = mild, 2 = moderate, 3 = severe).
Outcome measures
| Measure |
LF Formulation
n=322 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=321 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Number of Participants With Solicited General Adverse Events
Fatigue : Related Grade =3
|
14 participants
|
9 participants
|
|
Number of Participants With Solicited General Adverse Events
Body Temperature increased : All
|
23 participants
|
33 participants
|
|
Number of Participants With Solicited General Adverse Events
Body Temperature increased : Grade >=2
|
7 participants
|
8 participants
|
|
Number of Participants With Solicited General Adverse Events
Body Temperature increased : Grade =3
|
3 participants
|
2 participants
|
|
Number of Participants With Solicited General Adverse Events
Body Temperature increased : Related
|
22 participants
|
30 participants
|
|
Number of Participants With Solicited General Adverse Events
Body Temperature increased : Related Grade =3
|
3 participants
|
2 participants
|
|
Number of Participants With Solicited General Adverse Events
Headache : All
|
125 participants
|
112 participants
|
|
Number of Participants With Solicited General Adverse Events
Headache : Grade >=2
|
37 participants
|
27 participants
|
|
Number of Participants With Solicited General Adverse Events
Headache : Grade =3
|
8 participants
|
7 participants
|
|
Number of Participants With Solicited General Adverse Events
Headache : Related
|
110 participants
|
94 participants
|
|
Number of Participants With Solicited General Adverse Events
Headache : Related Grade =3
|
6 participants
|
6 participants
|
|
Number of Participants With Solicited General Adverse Events
Myalgia : All
|
68 participants
|
59 participants
|
|
Number of Participants With Solicited General Adverse Events
Myalgia : Grade >=2
|
24 participants
|
18 participants
|
|
Number of Participants With Solicited General Adverse Events
Myalgia : Grade =3
|
1 participants
|
5 participants
|
|
Number of Participants With Solicited General Adverse Events
Myalgia : Related
|
59 participants
|
47 participants
|
|
Number of Participants With Solicited General Adverse Events
Myalgia : Related Grade =3
|
1 participants
|
3 participants
|
|
Number of Participants With Solicited General Adverse Events
Chills : All
|
38 participants
|
35 participants
|
|
Number of Participants With Solicited General Adverse Events
Chills : Grade >=2
|
14 participants
|
10 participants
|
|
Number of Participants With Solicited General Adverse Events
Chills : Grade =3
|
2 participants
|
5 participants
|
|
Number of Participants With Solicited General Adverse Events
Chills : Related
|
34 participants
|
33 participants
|
|
Number of Participants With Solicited General Adverse Events
Chills : Related Grade =3
|
2 participants
|
4 participants
|
|
Number of Participants With Solicited General Adverse Events
Nausea : All
|
57 participants
|
51 participants
|
|
Number of Participants With Solicited General Adverse Events
Nausea : Grade >=2
|
19 participants
|
18 participants
|
|
Number of Participants With Solicited General Adverse Events
Nausea : Grade =3
|
4 participants
|
2 participants
|
|
Number of Participants With Solicited General Adverse Events
Nausea : Related
|
53 participants
|
44 participants
|
|
Number of Participants With Solicited General Adverse Events
Nausea : Related Grade =3
|
4 participants
|
2 participants
|
|
Number of Participants With Solicited General Adverse Events
Fatigue : All
|
113 participants
|
102 participants
|
|
Number of Participants With Solicited General Adverse Events
Fatigue : Grade >=2
|
39 participants
|
39 participants
|
|
Number of Participants With Solicited General Adverse Events
Fatigue : Grade =3
|
15 participants
|
9 participants
|
|
Number of Participants With Solicited General Adverse Events
Fatigue : Related
|
106 participants
|
95 participants
|
SECONDARY outcome
Timeframe: within 8 weeksPopulation: Per Protocol Analysis Set. Number Analyzed refers to the number of participants with measurements at the respective sampling time point.
Geometric Mean Titers (GMT) at all immunogenicity sampling time points based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). For the calculation of GMTs all measurements are included as they provide meaningful information even if below the detection limit (DL). Disregarding these measurements would highly bias the reported GMTs. We imputed values \<DL as a value of '1' and the GMT and corresponding 95% confidence intervals were calculated.
Outcome measures
| Measure |
LF Formulation
n=297 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=306 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
ELISA GMTs
Week 0
|
1.1 Titer
Interval 1.0 to 1.2
|
1.1 Titer
Interval 1.0 to 1.2
|
|
ELISA GMTs
Week 2
|
56.0 Titer
Interval 44.8 to 69.9
|
90.4 Titer
Interval 75.9 to 107.7
|
|
ELISA GMTs
Week 4
|
89.6 Titer
Interval 75.0 to 107.0
|
131.3 Titer
Interval 115.8 to 148.9
|
|
ELISA GMTs
Week 6
|
875.1 Titer
Interval 801.3 to 955.7
|
1099.6 Titer
Interval 1014.8 to 1191.6
|
|
ELISA GMTs
Week 8
|
546.4 Titer
Interval 499.4 to 597.8
|
689.0 Titer
Interval 635.2 to 747.4
|
SECONDARY outcome
Timeframe: Week 6Population: Per Protocol Analysis Set
Geometric Mean Titers (GMT) based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Titers below the detection limit are included with a value of '1'
Outcome measures
| Measure |
LF Formulation
n=297 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=306 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
PRNT GMT
|
81.8 Titer
Interval 73.0 to 91.6
|
101.2 Titer
Interval 91.0 to 112.5
|
SECONDARY outcome
Timeframe: within 8 weeksPopulation: Per Protocol Analysis Set. Number Analyzed refers to the number of participants with measurements at the respective sampling time point.
Geometric Mean Titers (GMT) at all immunogenicity sampling time points based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). For the calculation of GMTs all measurements are included as they provide meaningful information even if below the detection limit (DL). Disregarding these measurements would highly bias the reported GMTs. We imputed values \<DL as a value of '1' and the GMT and corresponding 95% confidence intervals were calculated.
Outcome measures
| Measure |
LF Formulation
n=297 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=306 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
PRNT GMTs
Week 0
|
1.1 Titer
Interval 1.0 to 1.1
|
1.0 Titer
Interval 1.0 to 1.1
|
|
PRNT GMTs
Week 2
|
7.1 Titer
Interval 6.0 to 8.6
|
10.4 Titer
Interval 8.7 to 12.3
|
|
PRNT GMTs
Week 4
|
9.3 Titer
Interval 7.9 to 11.1
|
12.5 Titer
Interval 10.6 to 14.7
|
|
PRNT GMTs
Week 6
|
81.8 Titer
Interval 73.0 to 91.6
|
101.2 Titer
Interval 91.0 to 112.5
|
|
PRNT GMTs
Week 8
|
59.7 Titer
Interval 54.0 to 66.0
|
76.1 Titer
Interval 69.6 to 83.2
|
SECONDARY outcome
Timeframe: Week 6Population: Per Protocol 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.
Outcome measures
| Measure |
LF Formulation
n=297 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=306 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Percentage of Participants With Seroconversion by ELISA
|
100.0 percentage of subjects
|
100.0 percentage of subjects
|
SECONDARY outcome
Timeframe: within 8 weeksPopulation: Per Protocol Analysis Set. Number Analyzed refers to the number of participants with measurements at the respective sampling time point.
Seroconversion rates at all post-baseline immunogenicity sampling time points 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 |
LF Formulation
n=297 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=306 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Percentage of Participants With Seroconversion by ELISA
Week 2
|
83.5 percentage of subjects
|
91.5 percentage of subjects
|
|
Percentage of Participants With Seroconversion by ELISA
Week 4
|
91.9 percentage of subjects
|
97.0 percentage of subjects
|
|
Percentage of Participants With Seroconversion by ELISA
Week 6
|
100.0 percentage of subjects
|
100.0 percentage of subjects
|
|
Percentage of Participants With Seroconversion by ELISA
Week 8
|
100.0 percentage of subjects
|
100.0 percentage of subjects
|
SECONDARY outcome
Timeframe: Week 6Population: Per Protocol Analysis Set
Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects.
Outcome measures
| Measure |
LF Formulation
n=297 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=306 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Percentage of Participants With Seroconversion by PRNT
|
99.0 percentage of subjects
|
100.0 percentage of subjects
|
SECONDARY outcome
Timeframe: within 8 weeksPopulation: Per Protocol Analysis Set. Number Analyzed refers to the number of participants with measurements at the respective sampling time point.
Seroconversion rates at all post-baseline immunogenicity sampling time points based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Outcome measures
| Measure |
LF Formulation
n=297 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=306 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Percentage of Participants With Seroconversion by PRNT
Week 2
|
80.1 percentage of subjects
|
87.3 percentage of subjects
|
|
Percentage of Participants With Seroconversion by PRNT
Week 4
|
84.8 percentage of subjects
|
91.5 percentage of subjects
|
|
Percentage of Participants With Seroconversion by PRNT
Week 6
|
99.0 percentage of subjects
|
100.0 percentage of subjects
|
|
Percentage of Participants With Seroconversion by PRNT
Week 8
|
100.0 percentage of subjects
|
99.7 percentage of subjects
|
SECONDARY outcome
Timeframe: within 8 weeksPopulation: ELISPOT Analysis Set
Magnitudes of response of IFNγ producing T-cells measured by vaccinica-specific ELISPOT. Spot Forming Units below the detection limit are included as a value of '1'.
Outcome measures
| Measure |
LF Formulation
n=101 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=94 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
ELISPOT Magnitudes of Response
Week 0
|
1.0 Spot Forming Units
Interval 1.0 to 1.0
|
1.0 Spot Forming Units
Interval 1.0 to 1.0
|
|
ELISPOT Magnitudes of Response
Week 2
|
393.0 Spot Forming Units
Interval 318.0 to 506.0
|
581.5 Spot Forming Units
Interval 416.0 to 718.0
|
|
ELISPOT Magnitudes of Response
Week 4
|
88.0 Spot Forming Units
Interval 70.0 to 107.0
|
133.0 Spot Forming Units
Interval 100.0 to 170.0
|
|
ELISPOT Magnitudes of Response
Week 6
|
235.0 Spot Forming Units
Interval 185.0 to 343.0
|
315.0 Spot Forming Units
Interval 232.0 to 412.0
|
|
ELISPOT Magnitudes of Response
Week 8
|
145.5 Spot Forming Units
Interval 115.0 to 174.0
|
240.0 Spot Forming Units
Interval 146.0 to 284.0
|
SECONDARY outcome
Timeframe: within 8 weeksPopulation: ELISPOT Analysis Set
Response rates regarding IFNγ producing T-cells measured by vaccinia-specific ELISPOT. A response to the vaccine was defined as either the appearance of a positive signal for participants without a positive signal at Baseline or an increase by a factor of at least 1.7 of the SFU/1 x 10E6 PBMC compared to the Baseline SFU/1 x 10E6 PBMC for participants with a positive signal at Baseline.
Outcome measures
| Measure |
LF Formulation
n=101 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=94 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Percentage of Participants With Response by ELISPOT
Week 2
|
95.0 percentage of subjects
|
97.9 percentage of subjects
|
|
Percentage of Participants With Response by ELISPOT
Week 4
|
66.0 percentage of subjects
|
80.2 percentage of subjects
|
|
Percentage of Participants With Response by ELISPOT
Week 6
|
88.0 percentage of subjects
|
94.4 percentage of subjects
|
|
Percentage of Participants With Response by ELISPOT
Week 8
|
84.0 percentage of subjects
|
92.3 percentage of subjects
|
SECONDARY outcome
Timeframe: within 8 weeksPopulation: ELISPOT Analysis Set
Responder rate measured by vaccinia specific ELISPOT. A participant was defined as a responder to the vaccine determined by ELISPOT if the participant had at least 1 post-baseline visit determined to be a response. A response to the vaccine was defined as either the appearance of a positive signal for participants without a positive signal at Baseline or an increase by a factor of at least 1.7 of the SFU/1 x 10E6 PBMC compared to the Baseline SFU/1 x 10E6 PBMC for participants with a positive signal at Baseline.
Outcome measures
| Measure |
LF Formulation
n=101 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=94 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Percentage of Responders by ELISPOT
|
100 percentage of subjects
|
100 percentage of subjects
|
SECONDARY outcome
Timeframe: within 8 weeksPopulation: Per Protocol Analysis Set
Pearson Correlation Coefficient between the ELISA titers and the PRNT titers at weeks 4, 6 and 8 based on the log10 transformed titer values
Outcome measures
| Measure |
LF Formulation
n=297 Participants
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=306 Participants
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Correlation ELISA vs PRNT Titers
Week 8
|
0.567 Pearson Correlation Coefficient
Interval 0.484 to 0.64
|
0.565 Pearson Correlation Coefficient
Interval 0.484 to 0.637
|
|
Correlation ELISA vs PRNT Titers
Week 4
|
0.597 Pearson Correlation Coefficient
Interval 0.518 to 0.665
|
0.492 Pearson Correlation Coefficient
Interval 0.401 to 0.572
|
|
Correlation ELISA vs PRNT Titers
Week 6
|
0.646 Pearson Correlation Coefficient
Interval 0.574 to 0.708
|
0.553 Pearson Correlation Coefficient
Interval 0.47 to 0.627
|
Adverse Events
LF Formulation
FD Formulation
Serious adverse events
| Measure |
LF Formulation
n=327 participants at risk
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=324 participants at risk
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
Blood and lymphatic system disorders
Haemolytic Anaemia
|
0.31%
1/327 • Number of events 1 • 32 weeks
|
0.00%
0/324 • 32 weeks
|
|
Infections and infestations
Subcutaneous Abscess
|
0.00%
0/327 • 32 weeks
|
0.31%
1/324 • Number of events 1 • 32 weeks
|
|
Injury, poisoning and procedural complications
Limb Injury
|
0.31%
1/327 • Number of events 1 • 32 weeks
|
0.00%
0/324 • 32 weeks
|
|
Metabolism and nutrition disorders
Diabetic Ketoacidosis
|
0.31%
1/327 • Number of events 1 • 32 weeks
|
0.00%
0/324 • 32 weeks
|
|
Nervous system disorders
Presyncope
|
0.31%
1/327 • Number of events 1 • 32 weeks
|
0.00%
0/324 • 32 weeks
|
|
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous
|
0.31%
1/327 • Number of events 1 • 32 weeks
|
0.00%
0/324 • 32 weeks
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/327 • 32 weeks
|
0.31%
1/324 • Number of events 1 • 32 weeks
|
Other adverse events
| Measure |
LF Formulation
n=327 participants at risk
Liquid Frozen formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
LF formulation of MVA-BN®
|
FD Formulation
n=324 participants at risk
Freeze Dried formulation of MVA-BN® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
FD formulation of MVA-BN®
|
|---|---|---|
|
General disorders
Injection site induration
|
23.5%
77/327 • 32 weeks
|
22.8%
74/324 • 32 weeks
|
|
General disorders
Injection site hemorrhage
|
0.61%
2/327 • 32 weeks
|
5.2%
17/324 • 32 weeks
|
|
General disorders
Injection site pain
|
1.8%
6/327 • 32 weeks
|
2.2%
7/324 • 32 weeks
|
|
General disorders
Injection site discoloration
|
1.5%
5/327 • 32 weeks
|
2.8%
9/324 • 32 weeks
|
|
General disorders
Injection site hematoma
|
1.5%
5/327 • 32 weeks
|
1.5%
5/324 • 32 weeks
|
|
General disorders
Fatigue
|
1.2%
4/327 • 32 weeks
|
0.00%
0/324 • 32 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
4.9%
16/327 • 32 weeks
|
5.9%
19/324 • 32 weeks
|
|
Infections and infestations
Viral upper respiratory tract infection
|
3.7%
12/327 • 32 weeks
|
2.5%
8/324 • 32 weeks
|
|
Nervous system disorders
Headache
|
2.4%
8/327 • 32 weeks
|
1.5%
5/324 • 32 weeks
|
|
Gastrointestinal disorders
Vomiting
|
1.2%
4/327 • 32 weeks
|
1.2%
4/324 • 32 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
1.8%
6/327 • 32 weeks
|
2.5%
8/324 • 32 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place