Trial Outcomes & Findings for Immunogenicity and Safety of Rabies Vaccine, Administered With Two Different Simulated Post Exposure Schedules (NCT NCT01365494)
NCT ID: NCT01365494
Last Updated: 2014-05-05
Results Overview
Immunogenicity was measured as the geometric mean concentrations (GMCs) of rabies virus neutralizing antibody (RVNA) titer , evaluated using the rapid fluorescent focus inhibition test, before vaccination and on study day 14 as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
250 participants
Primary outcome timeframe
On Day 0 and Day 14
Results posted on
2014-05-05
Participant Flow
Participant milestones
| Measure |
Zagreb
Rabipur vaccine, administered intramuscularly (IM) according to the 2-1-1 (Zagreb) schedule (i.e., 2 doses of vaccine administered on day 0 and 1 dose of vaccine each administered on day 7 and day 21)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Zagreb group received Rabipur vaccine intramuscularly according to either Zagreb schedule.
|
Essen
Rabipur vaccine, administered IM according to the 1-1-1-1-1 (Essen) schedule (i.e., 1 dose of vaccine administered on day 0, 3, 7, 14 and 28)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Essen group received Rabipur vaccine intramuscularly according to Essen schedule.
|
|---|---|---|
|
Overall Study
STARTED
|
126
|
124
|
|
Overall Study
COMPLETED
|
124
|
121
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
Zagreb
Rabipur vaccine, administered intramuscularly (IM) according to the 2-1-1 (Zagreb) schedule (i.e., 2 doses of vaccine administered on day 0 and 1 dose of vaccine each administered on day 7 and day 21)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Zagreb group received Rabipur vaccine intramuscularly according to either Zagreb schedule.
|
Essen
Rabipur vaccine, administered IM according to the 1-1-1-1-1 (Essen) schedule (i.e., 1 dose of vaccine administered on day 0, 3, 7, 14 and 28)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Essen group received Rabipur vaccine intramuscularly according to Essen schedule.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
Baseline Characteristics
Immunogenicity and Safety of Rabies Vaccine, Administered With Two Different Simulated Post Exposure Schedules
Baseline characteristics by cohort
| Measure |
Zagreb
n=126 Participants
Rabipur vaccine, administered intramuscularly (IM) according to the 2-1-1 (Zagreb) schedule (i.e., 2 doses of vaccine administered on day 0 and 1 dose of vaccine each administered on day 7 and day 21)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Zagreb group received Rabipur vaccine intramuscularly according to Zagreb schedules.
|
Essen
n=124 Participants
Rabipur vaccine, administered IM according to the 1-1-1-1-1 (Essen) schedule (i.e., 1 dose of vaccine administered on day 0, 3, 7, 14 and 28)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Essen group received Rabipur vaccine intramuscularly according to Essen schedules.
|
Total
n=250 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
29.1 years
STANDARD_DEVIATION 8.8 • n=99 Participants
|
27.2 years
STANDARD_DEVIATION 7.3 • n=107 Participants
|
28.2 years
STANDARD_DEVIATION 8.1 • n=206 Participants
|
|
Sex: Female, Male
Female
|
54 Participants
n=99 Participants
|
58 Participants
n=107 Participants
|
112 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
72 Participants
n=99 Participants
|
66 Participants
n=107 Participants
|
138 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: On Day 0 and Day 14Population: Per Protocol Set-All subjects in the FAS (Full analysis set) population who:correctly receive the vaccine, provide evaluable serum sample at day 14, and have no major protocol violation as defined prior to analysis
Immunogenicity was measured as the geometric mean concentrations (GMCs) of rabies virus neutralizing antibody (RVNA) titer , evaluated using the rapid fluorescent focus inhibition test, before vaccination and on study day 14 as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule
Outcome measures
| Measure |
Zagreb
n=124 Participants
Rabipur vaccine, administered intramuscularly (IM) according to the 2-1-1 (Zagreb) schedule (i.e., 2 doses of vaccine administered on day 0 and 1 dose of vaccine each administered on day 7 and day 21)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Zagreb group received Rabipur vaccine intramuscularly according to Zagreb schedule.
|
Essen
n=120 Participants
Rabipur vaccine, administered IM according to the 1-1-1-1-1 (Essen) schedule (i.e., 1 dose of vaccine administered on day 0, 3, 7, 14 and 28)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Essen group received Rabipur vaccine intramuscularly according to Essen schedule.
|
|---|---|---|
|
Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration in Each of the Zagreb and Essen Groups on Study Day 14
Day 0
|
0.09 IU/mL
Interval 0.076 to 0.11
|
0.099 IU/mL
Interval 0.083 to 0.12
|
|
Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration in Each of the Zagreb and Essen Groups on Study Day 14
Day 14
|
12 IU/mL
Interval 11.0 to 13.0
|
12 IU/mL
Interval 11.0 to 13.0
|
SECONDARY outcome
Timeframe: Study day 7, 14 and 42Population: Full Analysis Set- All subjects in the exposed population who provided at least one evaluable serum sample and as randomized
Immunogenicity was measured as the percentage of subjects who achieved anti-RVNA titer ≥0.5 IU/mL, at days 0, 7, 14 and 42 as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule.
Outcome measures
| Measure |
Zagreb
n=126 Participants
Rabipur vaccine, administered intramuscularly (IM) according to the 2-1-1 (Zagreb) schedule (i.e., 2 doses of vaccine administered on day 0 and 1 dose of vaccine each administered on day 7 and day 21)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Zagreb group received Rabipur vaccine intramuscularly according to Zagreb schedule.
|
Essen
n=123 Participants
Rabipur vaccine, administered IM according to the 1-1-1-1-1 (Essen) schedule (i.e., 1 dose of vaccine administered on day 0, 3, 7, 14 and 28)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Essen group received Rabipur vaccine intramuscularly according to Essen schedule.
|
|---|---|---|
|
Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Zagreb and Essen Groups at Days 7, 14 and 42
Day 0
|
6 Percentages of Subjects
Interval 3.0 to 12.0
|
9 Percentages of Subjects
Interval 5.0 to 15.0
|
|
Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Zagreb and Essen Groups at Days 7, 14 and 42
Day 7(N=125,123)
|
74 Percentages of Subjects
|
97 Percentages of Subjects
|
|
Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Zagreb and Essen Groups at Days 7, 14 and 42
Day 14(N=124,123)
|
100 Percentages of Subjects
|
100 Percentages of Subjects
|
|
Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Zagreb and Essen Groups at Days 7, 14 and 42
Day 42(N=124,121)
|
100 Percentages of Subjects
|
100 Percentages of Subjects
|
SECONDARY outcome
Timeframe: Day 0, Day 7, Day 14 and Day 42Population: Full Analysis Set- All subjects in the exposed population who provided at least one evaluable serum sample and as randomized
Immunogenicity was measured as the ratio of GMCs of RVNA titer , evaluated using the rapid fluorescent focus inhibition test, on Days 7 and 42 as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedules
Outcome measures
| Measure |
Zagreb
n=126 Participants
Rabipur vaccine, administered intramuscularly (IM) according to the 2-1-1 (Zagreb) schedule (i.e., 2 doses of vaccine administered on day 0 and 1 dose of vaccine each administered on day 7 and day 21)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Zagreb group received Rabipur vaccine intramuscularly according to Zagreb schedule.
|
Essen
n=123 Participants
Rabipur vaccine, administered IM according to the 1-1-1-1-1 (Essen) schedule (i.e., 1 dose of vaccine administered on day 0, 3, 7, 14 and 28)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Essen group received Rabipur vaccine intramuscularly according to Essen schedule.
|
|---|---|---|
|
Ratio of GMCs in Study Groups (Zagreb/Essen Schedules) on Days 7 and 42 as Measured by RVNA Geometric Mean Concentrations
Day 0
|
0.091 IU\ml
Interval 0.077 to 0.11
|
0.099 IU\ml
Interval 0.084 to 0.12
|
|
Ratio of GMCs in Study Groups (Zagreb/Essen Schedules) on Days 7 and 42 as Measured by RVNA Geometric Mean Concentrations
Day 7(N=125,123)
|
0.66 IU\ml
Interval 0.55 to 0.78
|
1.74 IU\ml
Interval 1.46 to 2.07
|
|
Ratio of GMCs in Study Groups (Zagreb/Essen Schedules) on Days 7 and 42 as Measured by RVNA Geometric Mean Concentrations
Day 14(N=124,123)
|
12 IU\ml
Interval 11.0 to 13.0
|
12 IU\ml
Interval 11.0 to 13.0
|
|
Ratio of GMCs in Study Groups (Zagreb/Essen Schedules) on Days 7 and 42 as Measured by RVNA Geometric Mean Concentrations
Day 42(N=124,121)
|
15 IU\ml
Interval 14.0 to 16.0
|
16 IU\ml
Interval 15.0 to 17.0
|
SECONDARY outcome
Timeframe: All reported SAEs and medically attended AEs or AEs that resulted in the premature withdrawal of subjects were collected up to 42 days after first vaccination. Adverse events were collected throughout the study periodPopulation: Safety population- All subjects in the Exposed population who provide post vaccination safety data and as vaccinated (as treated)
Adverse events (AEs) were collected for 7 days following administration of each study vaccination or until time of next vaccination (whichever occurred sooner). All reported SAEs and medically attended AEs or AEs that resulted in the premature withdrawal of subjects during the study were collected throughout the study period and all AEs were unsolicited.
Outcome measures
| Measure |
Zagreb
n=126 Participants
Rabipur vaccine, administered intramuscularly (IM) according to the 2-1-1 (Zagreb) schedule (i.e., 2 doses of vaccine administered on day 0 and 1 dose of vaccine each administered on day 7 and day 21)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Zagreb group received Rabipur vaccine intramuscularly according to Zagreb schedule.
|
Essen
n=123 Participants
Rabipur vaccine, administered IM according to the 1-1-1-1-1 (Essen) schedule (i.e., 1 dose of vaccine administered on day 0, 3, 7, 14 and 28)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Essen group received Rabipur vaccine intramuscularly according to Essen schedule.
|
|---|---|---|
|
Percentages of Subjects Reporting Adverse Events (AEs)
Any AEs
|
17 percentages of subjects
|
15 percentages of subjects
|
|
Percentages of Subjects Reporting Adverse Events (AEs)
At least possibly related AEs
|
4 percentages of subjects
|
11 percentages of subjects
|
|
Percentages of Subjects Reporting Adverse Events (AEs)
SAE
|
0 percentages of subjects
|
0 percentages of subjects
|
|
Percentages of Subjects Reporting Adverse Events (AEs)
At least possibly related SAEs
|
0 percentages of subjects
|
0 percentages of subjects
|
|
Percentages of Subjects Reporting Adverse Events (AEs)
Deaths
|
0 percentages of subjects
|
0 percentages of subjects
|
|
Percentages of Subjects Reporting Adverse Events (AEs)
Medically Attended AEs
|
0 percentages of subjects
|
0 percentages of subjects
|
|
Percentages of Subjects Reporting Adverse Events (AEs)
Withdrawal from study due to AE
|
0.8 percentages of subjects
|
0 percentages of subjects
|
Adverse Events
Zagreb
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Essen
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Zagreb
n=126 participants at risk
Rabipur vaccine, administered intramuscularly (IM) according to the 2-1-1 (Zagreb) schedule (i.e., 2 doses of vaccine administered on day 0 and 1 dose of vaccine each administered on day 7 and day 21)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Zagreb group received Rabipur vaccine intramuscularly according to Zagreb schedule.
|
Essen
n=123 participants at risk
Rabipur vaccine, administered IM according to the 1-1-1-1-1 (Essen) schedule (i.e., 1 dose of vaccine administered on day 0, 3, 7, 14 and 28)
Purified Chick Embryo Cell Inactivated Rabies Vaccine: Essen group received Rabipur vaccine intramuscularly according to Essen schedule.
|
|---|---|---|
|
General disorders
Injection site pain
|
2.4%
3/126 • All reported SAEs and medically attended AEs or AEs that resulted in the premature withdrawal of subjects were collected up to 42 days after first vaccination.
|
6.5%
8/123 • All reported SAEs and medically attended AEs or AEs that resulted in the premature withdrawal of subjects were collected up to 42 days after first vaccination.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreement with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publications of the pooled data (i.e., data from all sites) in the clinical trial
- Publication restrictions are in place
Restriction type: OTHER