Trial Outcomes & Findings for Safety and Immunogenicity of IMVAMUNE® (MVA-BN®) Smallpox Vaccine in HIV Infected Patients (NCT NCT00316589)
NCT ID: NCT00316589
Last Updated: 2019-01-03
Results Overview
Incidence, relationship and intensity of any Serious Adverse Event (SAE)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
581 participants
Primary outcome timeframe
within 32 weeks
Results posted on
2019-01-03
Participant Flow
Participant milestones
| Measure |
Healthy naïve
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
88
|
352
|
9
|
132
|
|
Overall Study
COMPLETED
|
87
|
328
|
8
|
127
|
|
Overall Study
NOT COMPLETED
|
1
|
24
|
1
|
5
|
Reasons for withdrawal
| Measure |
Healthy naïve
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
5
|
0
|
1
|
|
Overall Study
Subject unwilling/unable to comply
|
0
|
6
|
0
|
2
|
|
Overall Study
Adverse Event
|
1
|
0
|
0
|
1
|
|
Overall Study
Physician Decision
|
0
|
1
|
0
|
0
|
|
Overall Study
Other reason
|
0
|
12
|
1
|
1
|
Baseline Characteristics
Safety and Immunogenicity of IMVAMUNE® (MVA-BN®) Smallpox Vaccine in HIV Infected Patients
Baseline characteristics by cohort
| Measure |
Healthy naïve
n=88 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=351 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=9 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=131 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
Total
n=579 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
28.9 years
STANDARD_DEVIATION 7.14 • n=99 Participants
|
36.8 years
STANDARD_DEVIATION 7.98 • n=107 Participants
|
45.6 years
STANDARD_DEVIATION 8.88 • n=206 Participants
|
44.6 years
STANDARD_DEVIATION 5.13 • n=7 Participants
|
37.5 years
STANDARD_DEVIATION 8.80 • n=31 Participants
|
|
Sex: Female, Male
Female
|
50 Participants
n=99 Participants
|
64 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
21 Participants
n=7 Participants
|
139 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=99 Participants
|
287 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
110 Participants
n=7 Participants
|
440 Participants
n=31 Participants
|
|
Region of Enrollment
Puerto Rico
|
0 participants
n=99 Participants
|
27 participants
n=107 Participants
|
0 participants
n=206 Participants
|
7 participants
n=7 Participants
|
34 participants
n=31 Participants
|
|
Region of Enrollment
United States
|
88 participants
n=99 Participants
|
324 participants
n=107 Participants
|
9 participants
n=206 Participants
|
124 participants
n=7 Participants
|
545 participants
n=31 Participants
|
PRIMARY outcome
Timeframe: within 32 weeksPopulation: Full Analysis Set
Incidence, relationship and intensity of any Serious Adverse Event (SAE)
Outcome measures
| Measure |
Healthy naïve
n=88 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=351 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=9 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=131 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
Serious Adverse Events
Any SAE
|
0 Participants
|
17 Participants
|
0 Participants
|
6 Participants
|
|
Serious Adverse Events
Any SAE with intensity >= Grade 3
|
0 Participants
|
15 Participants
|
0 Participants
|
5 Participants
|
|
Serious Adverse Events
Any SAE assessed as related to vaccine
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: within 29 days after any vaccinationPopulation: Full Analysis set
Incidence of any Grade 3 or higher adverse drug reaction (missing, unknown, not evaluable, possibly, probably, or definitely related) to the study vaccine
Outcome measures
| Measure |
Healthy naïve
n=88 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=351 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=9 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=131 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
Related Grade >=3 Adverse Events
|
7 Participants
|
26 Participants
|
0 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: within 8 days after any vaccinationPopulation: Full Analysis Set
Incidence and intensity of solicited local AEs (pain, erythema, swelling). Percentages based on subjects with at least one completed diary card.
Outcome measures
| Measure |
Healthy naïve
n=88 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=351 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=9 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=131 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
Solicited Local Adverse Events
Pain: Any
|
79 Participants
|
246 Participants
|
7 Participants
|
79 Participants
|
|
Solicited Local Adverse Events
Pain: Grade >=3
|
9 Participants
|
28 Participants
|
1 Participants
|
4 Participants
|
|
Solicited Local Adverse Events
Erythema: Any
|
68 Participants
|
160 Participants
|
7 Participants
|
61 Participants
|
|
Solicited Local Adverse Events
Erythema: Grade >=3
|
2 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Solicited Local Adverse Events
Swelling: Any
|
56 Participants
|
139 Participants
|
6 Participants
|
52 Participants
|
|
Solicited Local Adverse Events
Swelling: Grade >=3
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: within 8 days after any vaccinationPopulation: Full Analysis Set
Incidence of solicited general AEs (increased body temperature, headache, myalgia, chills, nausea, and fatigue): Intensity and relationship to vaccination. Percentages based on subjects with at least one completed diary card.
Outcome measures
| Measure |
Healthy naïve
n=88 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=351 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=9 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=131 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
Solicited General Adverse Events
Increased body temperature: Any
|
9 Participants
|
26 Participants
|
1 Participants
|
15 Participants
|
|
Solicited General Adverse Events
Increased body temperature: Related
|
5 Participants
|
17 Participants
|
1 Participants
|
11 Participants
|
|
Solicited General Adverse Events
Increased body temperature: Grade >=3
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Solicited General Adverse Events
Headache: Any
|
40 Participants
|
117 Participants
|
1 Participants
|
29 Participants
|
|
Solicited General Adverse Events
Headache: Related
|
29 Participants
|
86 Participants
|
0 Participants
|
17 Participants
|
|
Solicited General Adverse Events
Headache: Grade >=3
|
5 Participants
|
11 Participants
|
0 Participants
|
5 Participants
|
|
Solicited General Adverse Events
Myalgia: Any
|
30 Participants
|
122 Participants
|
1 Participants
|
35 Participants
|
|
Solicited General Adverse Events
Myalgia: Related
|
28 Participants
|
100 Participants
|
1 Participants
|
26 Participants
|
|
Solicited General Adverse Events
Myalgia: Grade >=3
|
4 Participants
|
11 Participants
|
0 Participants
|
3 Participants
|
|
Solicited General Adverse Events
Chills: Any
|
12 Participants
|
58 Participants
|
0 Participants
|
11 Participants
|
|
Solicited General Adverse Events
Chills: Related
|
6 Participants
|
42 Participants
|
0 Participants
|
7 Participants
|
|
Solicited General Adverse Events
Chills: Grade >=3
|
0 Participants
|
3 Participants
|
0 Participants
|
1 Participants
|
|
Solicited General Adverse Events
Nausea: Any
|
15 Participants
|
52 Participants
|
0 Participants
|
22 Participants
|
|
Solicited General Adverse Events
Nausea: Related
|
12 Participants
|
42 Participants
|
0 Participants
|
12 Participants
|
|
Solicited General Adverse Events
Nausea: Grade >=3
|
3 Participants
|
7 Participants
|
0 Participants
|
4 Participants
|
|
Solicited General Adverse Events
Fatigue: Any
|
28 Participants
|
108 Participants
|
2 Participants
|
40 Participants
|
|
Solicited General Adverse Events
Fatigue: Related
|
22 Participants
|
84 Participants
|
1 Participants
|
29 Participants
|
|
Solicited General Adverse Events
Fatigue: Grade >=3
|
2 Participants
|
11 Participants
|
0 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: within 29 days after any vaccinationPopulation: Full Analysis Set
Incidence of any unsolicited adverse events
Outcome measures
| Measure |
Healthy naïve
n=88 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=351 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=9 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=131 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
Unsolicited Adverse Events: Incidence
|
59 Participants
|
236 Participants
|
3 Participants
|
73 Participants
|
SECONDARY outcome
Timeframe: within 29 days after any vaccinationPopulation: Full Analysis Set
Occurrence of unsolicited adverse events by Intensity
Outcome measures
| Measure |
Healthy naïve
n=88 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=351 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=9 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=131 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
Unsolicited Adverse Events: Intensity
Total
|
149 events
|
590 events
|
6 events
|
175 events
|
|
Unsolicited Adverse Events: Intensity
Grade 1
|
113 events
|
410 events
|
3 events
|
134 events
|
|
Unsolicited Adverse Events: Intensity
Grade 2
|
32 events
|
143 events
|
2 events
|
28 events
|
|
Unsolicited Adverse Events: Intensity
Grade 3
|
4 events
|
34 events
|
1 events
|
13 events
|
|
Unsolicited Adverse Events: Intensity
Grade 4
|
0 events
|
3 events
|
0 events
|
0 events
|
|
Unsolicited Adverse Events: Intensity
Missing
|
0 events
|
0 events
|
0 events
|
0 events
|
SECONDARY outcome
Timeframe: within 29 days after any vaccinationPopulation: Full Analysis Set
Occurrence of unsolicited adverse events by relationship to study vaccine
Outcome measures
| Measure |
Healthy naïve
n=88 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=351 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=9 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=131 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
Unsolicited Adverse Events: Relationship to Vaccination
Unrelated/None
|
45 events
|
236 events
|
0 events
|
87 events
|
|
Unsolicited Adverse Events: Relationship to Vaccination
Unlikely
|
40 events
|
167 events
|
1 events
|
42 events
|
|
Unsolicited Adverse Events: Relationship to Vaccination
Possible
|
22 events
|
109 events
|
1 events
|
23 events
|
|
Unsolicited Adverse Events: Relationship to Vaccination
Probable
|
16 events
|
45 events
|
1 events
|
12 events
|
|
Unsolicited Adverse Events: Relationship to Vaccination
Definite
|
26 events
|
31 events
|
3 events
|
11 events
|
|
Unsolicited Adverse Events: Relationship to Vaccination
Missing
|
0 events
|
2 events
|
0 events
|
0 events
|
|
Unsolicited Adverse Events: Relationship to Vaccination
Total
|
149 events
|
590 events
|
6 events
|
175 events
|
SECONDARY outcome
Timeframe: within 32 weeksPopulation: Full Analysis Set (HIV infected subjects)
Median CD4+ T-cell counts over time
Outcome measures
| Measure |
Healthy naïve
n=351 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=131 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
CD4+ T-cell Counts
Week 0
|
445.0 CD4 count (cells/µL)
Interval 156.0 to 1108.0
|
456.0 CD4 count (cells/µL)
Interval 186.0 to 922.0
|
—
|
—
|
|
CD4+ T-cell Counts
Week 1
|
434.5 CD4 count (cells/µL)
Interval 147.0 to 2029.0
|
455.0 CD4 count (cells/µL)
Interval 136.0 to 1107.0
|
—
|
—
|
|
CD4+ T-cell Counts
Week 6
|
438.5 CD4 count (cells/µL)
Interval 125.0 to 1045.0
|
447.0 CD4 count (cells/µL)
Interval 213.0 to 1081.0
|
—
|
—
|
|
CD4+ T-cell Counts
Week 32
|
403.5 CD4 count (cells/µL)
Interval 138.0 to 1056.0
|
435.0 CD4 count (cells/µL)
Interval 273.0 to 762.0
|
—
|
—
|
SECONDARY outcome
Timeframe: within 32 weeksPopulation: Full Analysis Set (HIV infected subjects)
Median CD8+ T-cell counts over time
Outcome measures
| Measure |
Healthy naïve
n=351 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=131 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
CD8+ T-cell Counts
Week 0
|
771.0 CD8 count (cells/µL)
Interval 62.0 to 3210.0
|
877.5 CD8 count (cells/µL)
Interval 188.0 to 1914.0
|
—
|
—
|
|
CD8+ T-cell Counts
Week 1
|
779.0 CD8 count (cells/µL)
Interval 208.0 to 3449.0
|
848.0 CD8 count (cells/µL)
Interval 219.0 to 2066.0
|
—
|
—
|
|
CD8+ T-cell Counts
Week 6
|
749.0 CD8 count (cells/µL)
Interval 177.0 to 3238.0
|
798.5 CD8 count (cells/µL)
Interval 229.0 to 2319.0
|
—
|
—
|
|
CD8+ T-cell Counts
Week 32
|
834.0 CD8 count (cells/µL)
Interval 196.0 to 2457.0
|
729.0 CD8 count (cells/µL)
Interval 245.0 to 1870.0
|
—
|
—
|
SECONDARY outcome
Timeframe: within 32 weeksPopulation: Full Analysis Set (HIV infected subjects)
Viral load (HIV-1 RNA levels) over time
Outcome measures
| Measure |
Healthy naïve
n=351 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=131 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
Viral Load
Week 0 · Missing
|
13 Participants
|
5 Participants
|
—
|
—
|
|
Viral Load
Week 0 · <400
|
262 Participants
|
112 Participants
|
—
|
—
|
|
Viral Load
Week 0 · 400 - <1000
|
11 Participants
|
3 Participants
|
—
|
—
|
|
Viral Load
Week 0 · 1000 - <10000
|
42 Participants
|
6 Participants
|
—
|
—
|
|
Viral Load
Week 0 · >=10000
|
23 Participants
|
5 Participants
|
—
|
—
|
|
Viral Load
Week 1 · Missing
|
15 Participants
|
7 Participants
|
—
|
—
|
|
Viral Load
Week 1 · <400
|
257 Participants
|
113 Participants
|
—
|
—
|
|
Viral Load
Week 1 · 400 - <1000
|
13 Participants
|
2 Participants
|
—
|
—
|
|
Viral Load
Week 1 · 1000 - <10000
|
44 Participants
|
5 Participants
|
—
|
—
|
|
Viral Load
Week 1 · >=10000
|
22 Participants
|
4 Participants
|
—
|
—
|
|
Viral Load
Week 6 · Missing
|
31 Participants
|
10 Participants
|
—
|
—
|
|
Viral Load
Week 6 · <400
|
240 Participants
|
105 Participants
|
—
|
—
|
|
Viral Load
Week 6 · 400 - <1000
|
18 Participants
|
3 Participants
|
—
|
—
|
|
Viral Load
Week 6 · 1000 - <10000
|
41 Participants
|
6 Participants
|
—
|
—
|
|
Viral Load
Week 6 · >=10000
|
21 Participants
|
7 Participants
|
—
|
—
|
|
Viral Load
Week 32 · Missing
|
275 Participants
|
108 Participants
|
—
|
—
|
|
Viral Load
Week 32 · <400
|
59 Participants
|
22 Participants
|
—
|
—
|
|
Viral Load
Week 32 · 400 - <1000
|
5 Participants
|
0 Participants
|
—
|
—
|
|
Viral Load
Week 32 · 1000 - <10000
|
4 Participants
|
1 Participants
|
—
|
—
|
|
Viral Load
Week 32 · >=10000
|
8 Participants
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: within 32 weeksPopulation: Per-protocol 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 |
Healthy naïve
n=57 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=241 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=5 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=91 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
PRNT Seroconversion Rate
Week 1
|
5.3 percentage of subjects
Interval 1.1 to 14.6
|
14.5 percentage of subjects
Interval 10.3 to 19.6
|
60.0 percentage of subjects
Interval 14.7 to 94.7
|
45.1 percentage of subjects
Interval 34.6 to 55.8
|
|
PRNT Seroconversion Rate
Week 4
|
17.5 percentage of subjects
Interval 8.7 to 29.9
|
21.6 percentage of subjects
Interval 16.6 to 27.3
|
60.0 percentage of subjects
Interval 14.7 to 94.7
|
62.6 percentage of subjects
Interval 51.9 to 72.6
|
|
PRNT Seroconversion Rate
Week 6
|
78.9 percentage of subjects
Interval 66.1 to 88.6
|
58.1 percentage of subjects
Interval 51.6 to 64.4
|
80.0 percentage of subjects
Interval 28.4 to 99.5
|
76.9 percentage of subjects
Interval 66.9 to 85.1
|
|
PRNT Seroconversion Rate
Week 8
|
78.9 percentage of subjects
Interval 66.1 to 88.6
|
52.7 percentage of subjects
Interval 46.2 to 59.1
|
80.0 percentage of subjects
Interval 28.4 to 99.5
|
78.0 percentage of subjects
Interval 68.1 to 86.0
|
|
PRNT Seroconversion Rate
Week 32
|
16.7 percentage of subjects
Interval 5.6 to 34.7
|
12.5 percentage of subjects
Interval 5.2 to 24.1
|
60.0 percentage of subjects
Interval 14.7 to 94.7
|
64.7 percentage of subjects
Interval 38.3 to 85.8
|
SECONDARY outcome
Timeframe: within 32 weeksPopulation: Per-protocol 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 |
Healthy naïve
n=57 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=241 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=5 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=91 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
PRNT GMT
Week 4
|
2.1 Titer
Interval 1.3 to 3.3
|
3.7 Titer
Interval 2.8 to 4.9
|
100.2 Titer
Interval 2.7 to 3721.7
|
42.3 Titer
Interval 26.9 to 66.4
|
|
PRNT GMT
Week 0
|
1.3 Titer
Interval 1.0 to 1.8
|
2.0 Titer
Interval 1.6 to 2.4
|
12.0 Titer
Interval 0.7 to 205.6
|
5.5 Titer
Interval 3.6 to 8.4
|
|
PRNT GMT
Week 1
|
1.6 Titer
Interval 1.1 to 2.4
|
2.9 Titer
Interval 2.2 to 3.7
|
108.9 Titer
Interval 2.9 to 4150.0
|
20.5 Titer
Interval 12.6 to 33.4
|
|
PRNT GMT
Week 6
|
20.8 Titer
Interval 12.3 to 35.3
|
13.0 Titer
Interval 9.6 to 17.5
|
354.5 Titer
Interval 66.2 to 1899.2
|
88.9 Titer
Interval 59.2 to 133.5
|
|
PRNT GMT
Week 8
|
14.8 Titer
Interval 9.2 to 24.0
|
9.7 Titer
Interval 7.2 to 12.9
|
171.2 Titer
Interval 62.2 to 470.9
|
76.1 Titer
Interval 52.0 to 111.4
|
|
PRNT GMT
Week 32
|
2.8 Titer
Interval 1.2 to 6.3
|
3.3 Titer
Interval 2.0 to 5.6
|
58.0 Titer
Interval 11.1 to 303.2
|
53.1 Titer
Interval 27.2 to 103.7
|
SECONDARY outcome
Timeframe: within 32 weeksPopulation: Per-protocol 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 |
Healthy naïve
n=57 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=241 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=5 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=91 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
ELISA Seroconversion Rate
Week 1
|
24.6 percentage of subjects
Interval 14.1 to 37.8
|
29.5 percentage of subjects
Interval 23.8 to 35.7
|
80.0 percentage of subjects
Interval 28.4 to 99.5
|
58.2 percentage of subjects
Interval 47.4 to 68.5
|
|
ELISA Seroconversion Rate
Week 4
|
80.7 percentage of subjects
Interval 68.1 to 90.0
|
69.3 percentage of subjects
Interval 63.1 to 75.1
|
100.0 percentage of subjects
Interval 47.8 to 100.0
|
79.1 percentage of subjects
Interval 69.3 to 86.9
|
|
ELISA Seroconversion Rate
Week 6
|
98.2 percentage of subjects
Interval 90.6 to 100.0
|
97.1 percentage of subjects
Interval 94.1 to 98.8
|
100.0 percentage of subjects
Interval 47.8 to 100.0
|
94.5 percentage of subjects
Interval 87.6 to 98.2
|
|
ELISA Seroconversion Rate
Week 8
|
96.5 percentage of subjects
Interval 87.9 to 99.6
|
92.1 percentage of subjects
Interval 88.0 to 95.2
|
100.0 percentage of subjects
Interval 47.8 to 100.0
|
90.1 percentage of subjects
Interval 82.1 to 95.4
|
|
ELISA Seroconversion Rate
Week 32
|
66.7 percentage of subjects
Interval 47.2 to 82.7
|
46.4 percentage of subjects
Interval 33.0 to 60.3
|
60.0 percentage of subjects
Interval 14.7 to 94.7
|
76.5 percentage of subjects
Interval 50.1 to 93.2
|
SECONDARY outcome
Timeframe: within 32 weeksPopulation: Per-protocol 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 |
Healthy naïve
n=57 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=241 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=5 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=91 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
ELISA GMT
Week 6
|
526.2 Titer
Interval 400.2 to 691.8
|
299.8 Titer
Interval 253.4 to 354.7
|
612.9 Titer
Interval 107.6 to 3490.5
|
588.4 Titer
Interval 463.6 to 746.7
|
|
ELISA GMT
Week 0
|
1.9 Titer
Interval 1.2 to 3.0
|
4.6 Titer
Interval 3.5 to 6.0
|
37.1 Titer
Interval 2.6 to 529.8
|
33.3 Titer
Interval 21.5 to 51.5
|
|
ELISA GMT
Week 1
|
3.7 Titer
Interval 2.1 to 6.5
|
9.4 Titer
Interval 6.9 to 12.8
|
260.6 Titer
Interval 36.6 to 1858.0
|
89.9 Titer
Interval 56.0 to 144.3
|
|
ELISA GMT
Week 4
|
56.2 Titer
Interval 34.9 to 90.5
|
46.6 Titer
Interval 35.7 to 60.9
|
461.1 Titer
Interval 63.8 to 3332.9
|
220.1 Titer
Interval 154.5 to 313.5
|
|
ELISA GMT
Week 8
|
312.9 Titer
Interval 235.5 to 415.8
|
175.5 Titer
Interval 143.6 to 214.6
|
403.4 Titer
Interval 77.0 to 2112.0
|
453.1 Titer
Interval 370.7 to 553.7
|
|
ELISA GMT
Week 32
|
32.1 Titer
Interval 14.7 to 70.1
|
24.3 Titer
Interval 12.7 to 46.5
|
89.5 Titer
Interval 3.6 to 2230.7
|
203.9 Titer
Interval 152.7 to 272.4
|
SECONDARY outcome
Timeframe: within 32 weeksPopulation: Elispot Analysis Set (subset of the Per-protocol Set with ELISPOT data available)
Response rate based on number of subjects with response in an interferon gamma (IFN-γ) ELISPOT assay. Response is defined as the appearance of a signal in subjects that had no signal at Baseline or a relative increase by a factor of ≥1.7 compared to Baseline in subjects that had a signal at Baseline. Percentages based on number of subjects with data available.
Outcome measures
| Measure |
Healthy naïve
n=23 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=35 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=3 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=68 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
ELISPOT IFN-γ: Response Rate
Week 1
|
39.1 percentage of subjects
Interval 19.7 to 61.5
|
28.6 percentage of subjects
Interval 14.6 to 46.3
|
0.0 percentage of subjects
Interval 0.0 to 70.8
|
26.5 percentage of subjects
Interval 16.5 to 38.6
|
|
ELISPOT IFN-γ: Response Rate
Week 4
|
39.1 percentage of subjects
Interval 19.7 to 61.5
|
20.0 percentage of subjects
Interval 8.4 to 36.9
|
33.3 percentage of subjects
Interval 0.8 to 90.6
|
29.4 percentage of subjects
Interval 19.0 to 41.7
|
|
ELISPOT IFN-γ: Response Rate
Week 6
|
47.8 percentage of subjects
Interval 26.8 to 69.4
|
40.0 percentage of subjects
Interval 23.9 to 57.9
|
0.0 percentage of subjects
Interval 0.0 to 70.8
|
29.4 percentage of subjects
Interval 19.0 to 41.7
|
|
ELISPOT IFN-γ: Response Rate
Week 8
|
30.4 percentage of subjects
Interval 13.2 to 52.9
|
25.7 percentage of subjects
Interval 12.5 to 43.3
|
0.0 percentage of subjects
Interval 0.0 to 70.8
|
29.4 percentage of subjects
Interval 19.0 to 41.7
|
|
ELISPOT IFN-γ: Response Rate
Week 32
|
52.4 percentage of subjects
Interval 29.8 to 74.3
|
36.8 percentage of subjects
Interval 16.3 to 61.6
|
50.0 percentage of subjects
Interval 1.3 to 98.7
|
23.1 percentage of subjects
Interval 5.0 to 53.8
|
SECONDARY outcome
Timeframe: within 32 weeksPopulation: Elispot Analysis Set (subset of the Per-protocol Set with ELISPOT data available)
Median number of interferon gamma (IFN-γ) secreting peripheral blood mononuclear cells (PBMC) in response to stimulation with MVA-BN detected by ELISPOT assay.
Outcome measures
| Measure |
Healthy naïve
n=23 Participants
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=35 Participants
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=3 Participants
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=68 Participants
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
ELISPOT IFN-γ: SFU
Week 0
|
0.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 230.0
|
0.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 239.0
|
155.0 Spot Forming Units / 10^6 PBMC
Interval 88.0 to 542.0
|
0.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 233.0
|
|
ELISPOT IFN-γ: SFU
Week 1
|
87.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 497.0
|
0.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 806.0
|
71.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 322.0
|
0.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 375.0
|
|
ELISPOT IFN-γ: SFU
Week 4
|
93.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 501.0
|
0.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 371.0
|
569.0 Spot Forming Units / 10^6 PBMC
Interval 100.0 to 1143.0
|
0.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 603.0
|
|
ELISPOT IFN-γ: SFU
Week 6
|
99.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 754.0
|
72.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 822.0
|
54.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 751.0
|
57.5 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 570.0
|
|
ELISPOT IFN-γ: SFU
Week 8
|
0.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 599.0
|
0.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 505.0
|
71.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 96.0
|
53.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 550.0
|
|
ELISPOT IFN-γ: SFU
Week 32
|
71.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 942.0
|
73.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 370.0
|
596.0 Spot Forming Units / 10^6 PBMC
Interval 454.0 to 738.0
|
0.0 Spot Forming Units / 10^6 PBMC
Interval 0.0 to 365.0
|
Adverse Events
Healthy naïve
Serious events: 0 serious events
Other events: 51 other events
Deaths: 0 deaths
HIV naïve
Serious events: 17 serious events
Other events: 172 other events
Deaths: 1 deaths
Healthy Experienced
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
HIV Experienced
Serious events: 6 serious events
Other events: 45 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Healthy naïve
n=88 participants at risk
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=351 participants at risk
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=9 participants at risk
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=131 participants at risk
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
Infections and infestations
Neurosyphilis
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Infections and infestations
Peritonsillar abscess
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Infections and infestations
Sepsis
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/88
|
0.57%
2/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Injury, poisoning and procedural complications
Jaw fracture
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Infections and infestations
Bronchitis acute
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Respiratory, thoracic and mediastinal disorders
Status asthmaticus
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
General disorders
Pyrexia
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Infections and infestations
Pneumonia
|
0.00%
0/88
|
0.57%
2/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Injury, poisoning and procedural complications
Back injury
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Injury, poisoning and procedural complications
Anticonvulsant toxicity
|
0.00%
0/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/88
|
0.00%
0/351
|
0.00%
0/9
|
1.5%
2/131
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/88
|
0.00%
0/351
|
0.00%
0/9
|
0.76%
1/131
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/88
|
0.00%
0/351
|
0.00%
0/9
|
0.76%
1/131
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/88
|
0.00%
0/351
|
0.00%
0/9
|
0.76%
1/131
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.00%
0/88
|
0.00%
0/351
|
0.00%
0/9
|
0.76%
1/131
|
|
Infections and infestations
Gangrene
|
0.00%
0/88
|
0.00%
0/351
|
0.00%
0/9
|
0.76%
1/131
|
Other adverse events
| Measure |
Healthy naïve
n=88 participants at risk
Healthy, smallpox vaccine-naïve subjects
|
HIV naïve
n=351 participants at risk
HIV-infected, smallpox vaccine-naïve subjects
|
Healthy Experienced
n=9 participants at risk
Healthy, smallpox vaccine-experienced subjects
|
HIV Experienced
n=131 participants at risk
HIV-infected, smallpox vaccine-experienced subjects
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
2.3%
2/88
|
4.0%
14/351
|
0.00%
0/9
|
4.6%
6/131
|
|
Gastrointestinal disorders
Nausea
|
2.3%
2/88
|
2.6%
9/351
|
0.00%
0/9
|
1.5%
2/131
|
|
Gastrointestinal disorders
Vomiting
|
4.5%
4/88
|
0.28%
1/351
|
0.00%
0/9
|
0.76%
1/131
|
|
General disorders
Injection site bruising
|
2.3%
2/88
|
0.57%
2/351
|
0.00%
0/9
|
0.00%
0/131
|
|
General disorders
Injection site nodule
|
3.4%
3/88
|
1.7%
6/351
|
11.1%
1/9
|
0.00%
0/131
|
|
General disorders
Injection site pain
|
2.3%
2/88
|
0.85%
3/351
|
0.00%
0/9
|
0.00%
0/131
|
|
General disorders
Injection site pruritis
|
25.0%
22/88
|
18.8%
66/351
|
22.2%
2/9
|
16.8%
22/131
|
|
General disorders
Injection site warmth
|
2.3%
2/88
|
0.57%
2/351
|
0.00%
0/9
|
0.76%
1/131
|
|
General disorders
Pyrexia
|
0.00%
0/88
|
2.3%
8/351
|
11.1%
1/9
|
0.00%
0/131
|
|
Infections and infestations
Herpes simplex
|
0.00%
0/88
|
0.00%
0/351
|
0.00%
0/9
|
2.3%
3/131
|
|
Infections and infestations
Nasopharyngitis
|
1.1%
1/88
|
2.8%
10/351
|
0.00%
0/9
|
0.76%
1/131
|
|
Infections and infestations
Sinusitis
|
5.7%
5/88
|
1.7%
6/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Investigations
Blood bilirubin increased
|
1.1%
1/88
|
2.0%
7/351
|
0.00%
0/9
|
1.5%
2/131
|
|
Investigations
Electrocardiogram abnormal
|
2.3%
2/88
|
0.57%
2/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Investigations
Troponin I increased
|
10.2%
9/88
|
8.8%
31/351
|
0.00%
0/9
|
5.3%
7/131
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.1%
1/88
|
1.4%
5/351
|
0.00%
0/9
|
2.3%
3/131
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.1%
1/88
|
0.85%
3/351
|
0.00%
0/9
|
2.3%
3/131
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.3%
2/88
|
0.57%
2/351
|
0.00%
0/9
|
0.76%
1/131
|
|
Nervous system disorders
Dizziness
|
1.1%
1/88
|
3.4%
12/351
|
0.00%
0/9
|
1.5%
2/131
|
|
Nervous system disorders
Headache
|
5.7%
5/88
|
2.3%
8/351
|
0.00%
0/9
|
2.3%
3/131
|
|
Nervous system disorders
Syncope
|
2.3%
2/88
|
0.00%
0/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
2.3%
2/88
|
0.00%
0/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/88
|
4.6%
16/351
|
0.00%
0/9
|
2.3%
3/131
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
2.3%
2/88
|
3.1%
11/351
|
0.00%
0/9
|
0.76%
1/131
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
4.5%
4/88
|
3.4%
12/351
|
11.1%
1/9
|
3.8%
5/131
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
2.3%
2/88
|
0.57%
2/351
|
0.00%
0/9
|
0.76%
1/131
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
2.3%
2/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
3.4%
3/88
|
1.4%
5/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
2.3%
2/88
|
2.6%
9/351
|
0.00%
0/9
|
0.00%
0/131
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/88
|
1.1%
4/351
|
0.00%
0/9
|
3.1%
4/131
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
2.3%
2/88
|
0.28%
1/351
|
0.00%
0/9
|
0.00%
0/131
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place