Trial Outcomes & Findings for Safety and Effectiveness of BPL HRIG With Active Rabies Vaccine in Healthy Subjects (NCT NCT03264157)
NCT ID: NCT03264157
Last Updated: 2020-02-25
Results Overview
Non-inferiority in terms of the proportion of subjects with anti-rabies antibody titer of ≥0.5 IU/mL after study drug administration using a non-inferiority margin of 10%.
COMPLETED
PHASE2/PHASE3
162 participants
Day 14
2020-02-25
Participant Flow
Participant milestones
| Measure |
BPL HRIG + RabAvert
20 IU/kg dose HRIG + active rabies vaccine
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
Comparator HyperRab + RabAvert
20 IU/kg dose HRIG + active rabies vaccine
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
|---|---|---|
|
Overall Study
STARTED
|
81
|
81
|
|
Overall Study
COMPLETED
|
68
|
74
|
|
Overall Study
NOT COMPLETED
|
13
|
7
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Effectiveness of BPL HRIG With Active Rabies Vaccine in Healthy Subjects
Baseline characteristics by cohort
| Measure |
BPL HRIG + RabAvert
n=81 Participants
20 IU/kg dose HRIG + active rabies vaccine
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
Comparator HyperRab + RabAvert
n=81 Participants
20 IU/kg dose HRIG + active rabies vaccine
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
Total
n=162 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
41.37 years
STANDARD_DEVIATION 15.0 • n=5 Participants
|
44.56 years
STANDARD_DEVIATION 15.4 • n=7 Participants
|
42.96 years
STANDARD_DEVIATION 15.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
56 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
110 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
79 Participants
n=5 Participants
|
78 Participants
n=7 Participants
|
157 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
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
16 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
62 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
121 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
81 participants
n=5 Participants
|
81 participants
n=7 Participants
|
162 participants
n=5 Participants
|
|
Weight
|
74.61 kg
STANDARD_DEVIATION 12.5 • n=5 Participants
|
74.51 kg
STANDARD_DEVIATION 13.2 • n=7 Participants
|
74.56 kg
STANDARD_DEVIATION 12.8 • n=5 Participants
|
PRIMARY outcome
Timeframe: Day 14Population: Primary PK population (all subjects who receive the full dose of BPL HRIG or comparator HRIG and the first 3 doses of active rabies vaccine on Days 0, 3, 7 and for whom the PK sample at Day 14 is taken).
Non-inferiority in terms of the proportion of subjects with anti-rabies antibody titer of ≥0.5 IU/mL after study drug administration using a non-inferiority margin of 10%.
Outcome measures
| Measure |
BPL HRIG + RabAvert
n=73 Participants
20 IU/kg dose HRIG + active rabies vaccine
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
Comparator HyperRab + RabAvert
n=74 Participants
20 IU/kg dose HRIG + active rabies vaccine
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
|---|---|---|
|
Proportion of Subjects With Anti-rabies Antibody Titer of ≥0.5 IU/mL
|
73 Participants
|
72 Participants
|
SECONDARY outcome
Timeframe: Day 0 to Day 7Population: Primary PK population (all subjects who receive the full dose of BPL HRIG or comparator HRIG and the first 3 doses of active rabies vaccine on Days 0, 3, 7 and for whom the PK sample at Day 14 is taken).
The AUC0-7d for BPL HRIG and vaccine versus comparator HRIG and vaccine using a non inferiority margin of 20%.
Outcome measures
| Measure |
BPL HRIG + RabAvert
n=73 Participants
20 IU/kg dose HRIG + active rabies vaccine
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
Comparator HyperRab + RabAvert
n=74 Participants
20 IU/kg dose HRIG + active rabies vaccine
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
|---|---|---|
|
Analysis of AUC0-7d
|
1.10 day*IU/mL
Interval 1.02 to 1.2
|
1.32 day*IU/mL
Interval 1.21 to 1.44
|
SECONDARY outcome
Timeframe: Days 3, 5, 7 and 14Population: Secondary PK population (subjects who receive the full dose of BPL HRIG or comparator HRIG and all 5 doses of active rabies vaccine and for whom all required PK samples are taken).
Comparison of the geometric mean titers (GMTs) for antirabies antibody titer after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine. The median peak RVNA titer occurred at Day 14, which is reflected in the analysis. The RVNA titer to peak geometric mean is analyzed using a repeated measures analysis. The inferential test compares RVNA values between BPL HRIG and HyperRab in a single analysis across all visits at or below the visit at which peak titer is observed. The geometric mean values presented represent a mean across all visits from baseline through and including Day 14.
Outcome measures
| Measure |
BPL HRIG + RabAvert
n=61 Participants
20 IU/kg dose HRIG + active rabies vaccine
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
Comparator HyperRab + RabAvert
n=69 Participants
20 IU/kg dose HRIG + active rabies vaccine
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
|---|---|---|
|
RVNA Geometric Mean Titers at Days 3, 5, 7 and 14
Through Day 14
|
0.37 IU/mL
Interval 0.35 to 0.39
|
0.38 IU/mL
Interval 0.36 to 0.4
|
|
RVNA Geometric Mean Titers at Days 3, 5, 7 and 14
Day 3
|
0.18 IU/mL
Interval 0.16 to 0.2
|
0.21 IU/mL
Interval 0.19 to 0.24
|
|
RVNA Geometric Mean Titers at Days 3, 5, 7 and 14
Day 5
|
0.19 IU/mL
Interval 0.18 to 0.21
|
0.24 IU/mL
Interval 0.21 to 0.26
|
|
RVNA Geometric Mean Titers at Days 3, 5, 7 and 14
Day 7
|
0.23 IU/mL
Interval 0.21 to 0.26
|
0.26 IU/mL
Interval 0.23 to 0.29
|
|
RVNA Geometric Mean Titers at Days 3, 5, 7 and 14
Day 14
|
12.30 IU/mL
Interval 10.15 to 14.9
|
8.38 IU/mL
Interval 6.54 to 10.74
|
SECONDARY outcome
Timeframe: Days 3, 5, 7, 14, 28, 49, and 140Population: Primary PK population (all subjects who receive the full dose of BPL HRIG or comparator HRIG and the first 3 doses of active rabies vaccine on Days 0, 3, 7 and for whom the PK sample at Day 14 is taken).
The proportion of subjects reaching antirabies antibody titer of ≥ 0.5 IU/mL after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine.
Outcome measures
| Measure |
BPL HRIG + RabAvert
n=73 Participants
20 IU/kg dose HRIG + active rabies vaccine
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
Comparator HyperRab + RabAvert
n=74 Participants
20 IU/kg dose HRIG + active rabies vaccine
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
|---|---|---|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit
Day 0
|
0 Participants
|
0 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit
Day 3
|
0 Participants
|
1 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit
Day 5
|
0 Participants
|
1 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit
Day 7
|
3 Participants
|
2 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit
Day 14
|
73 Participants
|
72 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit
Day 28
|
73 Participants
|
73 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit
Day 49
|
73 Participants
|
72 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit
Day 140
|
60 Participants
|
65 Participants
|
SECONDARY outcome
Timeframe: Days 3, 5, 7, 14, 28, 49, and 140Population: Primary PK population (all subjects who receive the full dose of BPL HRIG or comparator HRIG and the first 3 doses of active rabies vaccine on Days 0, 3, 7 and for whom the PK sample at Day 14 is taken).
The proportion of subjects reaching antirabies antibody titer of ≥ LLOQ of the assay at each visit after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine.
Outcome measures
| Measure |
BPL HRIG + RabAvert
n=73 Participants
20 IU/kg dose HRIG + active rabies vaccine
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
Comparator HyperRab + RabAvert
n=74 Participants
20 IU/kg dose HRIG + active rabies vaccine
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
|---|---|---|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit
Day 0
|
0 Participants
|
0 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit
Day 3
|
70 Participants
|
73 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit
Day 5
|
71 Participants
|
74 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit
Day 7
|
73 Participants
|
74 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit
Day 14
|
73 Participants
|
74 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit
Day 28
|
73 Participants
|
74 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit
Day 49
|
73 Participants
|
72 Participants
|
|
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit
Day 140
|
62 Participants
|
71 Participants
|
SECONDARY outcome
Timeframe: Days 14, 28, 49 and 140Population: Secondary PK population (subjects who receive the full dose of BPL HRIG or comparator HRIG and all 5 doses of active rabies vaccine and for whom all required PK samples are taken).
Comparison of the GMTs for antirabies antibody titer after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine to assess the inhibitory effects of BPL HRIG on active immunization relative to that of the comparator HRIG.
Outcome measures
| Measure |
BPL HRIG + RabAvert
n=61 Participants
20 IU/kg dose HRIG + active rabies vaccine
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
Comparator HyperRab + RabAvert
n=69 Participants
20 IU/kg dose HRIG + active rabies vaccine
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
|---|---|---|
|
RVNA Geometric Mean Titers at Days 14, 28, 49 and 140
Day 14
|
12.30 IU/mL
Interval 10.15 to 14.9
|
8.38 IU/mL
Interval 6.54 to 10.74
|
|
RVNA Geometric Mean Titers at Days 14, 28, 49 and 140
Day 28
|
10.18 IU/mL
Interval 8.39 to 12.34
|
7.78 IU/mL
Interval 6.26 to 9.66
|
|
RVNA Geometric Mean Titers at Days 14, 28, 49 and 140
Day 49
|
10.91 IU/mL
Interval 8.94 to 13.32
|
7.78 IU/mL
Interval 6.34 to 9.56
|
|
RVNA Geometric Mean Titers at Days 14, 28, 49 and 140
Day 140
|
2.72 IU/mL
Interval 2.21 to 3.34
|
2.02 IU/mL
Interval 1.62 to 2.53
|
Adverse Events
BPL HRIG + RabAvert
Comparator HyperRab + RabAvert
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
BPL HRIG + RabAvert
n=81 participants at risk
20 IU/kg dose HRIG + active rabies vaccine
HRIG: A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
Comparator HyperRab + RabAvert
n=81 participants at risk
20 IU/kg dose HRIG + active rabies vaccine
HyperRAB: A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.
RabAvert: A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.
|
|---|---|---|
|
General disorders
Vaccination site pain
|
11.1%
9/81 • Number of events 10 • 20 weeks treatment
Includes treatment emergent adverse events
|
2.5%
2/81 • Number of events 3 • 20 weeks treatment
Includes treatment emergent adverse events
|
|
Infections and infestations
Upper respiratory tract infection
|
6.2%
5/81 • Number of events 5 • 20 weeks treatment
Includes treatment emergent adverse events
|
8.6%
7/81 • Number of events 7 • 20 weeks treatment
Includes treatment emergent adverse events
|
|
Nervous system disorders
Headache
|
6.2%
5/81 • Number of events 5 • 20 weeks treatment
Includes treatment emergent adverse events
|
12.3%
10/81 • Number of events 12 • 20 weeks treatment
Includes treatment emergent adverse events
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER