Rabies
Conditions
Keywords
vaccine, prevention, rabies, Rabies disease
Brief summary
This study investigates the safety and immunogenicity (non-inferiority) of a Purified Chick Embryo Cell Vaccine (PCECV) administered in two different schedules (conventional versus abbreviated schedule) in healthy adults 18 to 50 years of age in China
Interventions
BIOLOGICALAbbreviated Zagreb 2-1-1 schedule
Subjects received the abbreviated Zagreb 2-1-1 schedule in a safety-lead-in phase.
BIOLOGICALStandard Essen 1-1-1-1-1 schedule
Subjects received the standard Essen regimen.
Sponsors
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female subjects 18-50 years of age who: * are in good health at the time of entry into the study as determined by medical history, physical examination and clinical judgment of the investigator; * volunteer for the simulated post-exposure vaccination courses and blood draws; * have given a written informed consent; informed consent must be obtained for all the subjects before enrolment in the study; * are available for all the visits scheduled in the study.
Exclusion criteria
* Subjects with the below criteria were excluded: * pregnancy or unwillingness to practice acceptable contraception during participation in the study; * a history of rabies immunization; * a significant acute or chronic infectious disease that may impact the subject's safety and /or immunogenicity in the Investigators opinion at the time of enrolment; * fever ≥ 38.0°C (axillary) or/and significant acute or chronic infection requiring systemic antibiotic or antiviral therapy within the past 7 days before enrolment; * treatment with corticosteroids, immunosuppressive or antimalaria drugs during the two month period before enrolment; * administration of any vaccine within the past 14 days before enrolment; * known/suspected immunodeficiency, or autoimmune disease, or any immunologic disorder; * history of allergy to egg protein; * known hypersensitivity to neomycin, tetracycline, amphotericin-B, or any other vaccine component; * treatment with parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within the past 3 months; * mental condition rendering the subject unable to understand the nature, scope and consequences of the study; * participation in any other investigational trial within the past 3 months before enrolment; * planned surgery during the study period; * intention to leave the area of the study site before the end of study period; * any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objective.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rabies Virus Neutralizing Antibody Concentrations on Day 14. | 14 days | Rabies virus neutralizing antibody concentrations of the abbreviated Zagreb regimen compared with the conventional Essen regimen. Results are presented on log2 scale. For results on original geometric (multiplicative) scale please raise numbers to the basis of 2. |
| Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | 7 days after each vaccination | Specified local and systemic reactions were solicited for 7 days after each vaccination. Number of participants were calculated who reported a local or systemic reaction after any of the vaccinations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rabies Virus Neutralizing Antibody Concentrations on Day 7 and Day 42. | 7 days and 42 days | Rabies virus neutralizing antibody concentrations the abbreviated Zagreb regimen compared with the conventional Essen regimen. Results are presented on log2 scale. For results on original geometric (multiplicative) scale please raise numbers to the basis of 2. |
| Percentages of Participants With Seroconversion (Rabies Virus Neutralizing Antibody Concentrations Equal and Above 0.5 IU/ml) on Days 7, 14 and 42. | 7 days, 14 days and 42 days | Percentages of participants with seroconversion (defined as rabies virus neutralizing antibody concentrations equal and above 0.5 IU/ml) on days 7, 14 and 42. |
Countries
China
Participant flow
Recruitment details
Study participants were enrolled in November 2008 at 1 center in China.
Pre-assignment details
All enrolled subjects were randomized, but one subject in the Zagreb (2-1-1) group was not vaccinated.
Participants by arm
| Arm | Count |
|---|---|
| Abbreviated Zagreb (2-1-1) Abbreviated Zagreb vaccination schedule with 2 vaccinations at day 0, 1 vaccination at day 7 and 1 vaccination at day 21. | 549 |
| Conventional Essen(1-1-1-1-1) Conventional Essen schedule with 1 vaccination on day 0, day 3, day 7, day 14 and day 28, respectively. | 275 |
| Total | 824 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Can not be classified | 0 | 1 |
| Overall Study | Inappropriate inclusion | 1 | 0 |
| Overall Study | Protocol Violation | 9 | 9 |
| Overall Study | Withdrawal by Subject | 6 | 12 |
Baseline characteristics
| Characteristic | Abbreviated Zagreb (2-1-1) | Conventional Essen(1-1-1-1-1) | Total |
|---|---|---|---|
| Age Continuous | 38.2 years STANDARD_DEVIATION 7.14 | 39.33 years STANDARD_DEVIATION 6.93 | 38.58 years STANDARD_DEVIATION 7.09 |
| Sex: Female, Male Female | 323 Participants | 154 Participants | 477 Participants |
| Sex: Female, Male Male | 226 Participants | 121 Participants | 347 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 52 / 549 | 26 / 275 |
| serious Total, serious adverse events | 0 / 549 | 1 / 275 |
Outcome results
Primary
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination
Specified local and systemic reactions were solicited for 7 days after each vaccination. Number of participants were calculated who reported a local or systemic reaction after any of the vaccinations.
Time frame: 7 days after each vaccination
Population: Safety was analyzed for the safety set. One enrolled subject was not vaccinated and not included in the safety set because of inappropriate inclusion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Pain | 475 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Any local reaction | 483 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Erythema | 37 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Swelling | 42 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Any systemic reaction | 177 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Chills | 21 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Malaise | 35 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Headache | 91 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Nausea | 28 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Myalgia | 29 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Arthralgia | 13 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Fatigue | 61 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Rash | 3 participants |
| Abbreviated Zagreb (2-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Fever ≥37.1°C | 124 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Arthralgia | 13 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Headache | 49 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Any local reaction | 241 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Rash | 33 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Erythema | 18 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Nausea | 24 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Swelling | 38 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Pain | 236 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Fatigue | 34 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Any systemic reaction | 103 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Myalgia | 23 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Chills | 8 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Fever ≥37.1°C | 68 participants |
| Conventional Essen(1-1-1-1-1) | Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination | Malaise | 17 participants |
Primary
Rabies Virus Neutralizing Antibody Concentrations on Day 14.
Rabies virus neutralizing antibody concentrations of the abbreviated Zagreb regimen compared with the conventional Essen regimen. Results are presented on log2 scale. For results on original geometric (multiplicative) scale please raise numbers to the basis of 2.
Time frame: 14 days
Population: Due to the Chinese registration requirements, only a subset of subjects bloodsamples were drawn and immunogenicity was evaluated. The per protocol population of this subset was analyzed.
| Arm | Measure | Value (LOG_MEAN) |
|---|---|---|
| Abbreviated Zagreb (2-1-1) | Rabies Virus Neutralizing Antibody Concentrations on Day 14. | 3.1 IU/mL |
| Conventional Essen(1-1-1-1-1) | Rabies Virus Neutralizing Antibody Concentrations on Day 14. | 3.3 IU/mL |
95% CI: [-0.81, 0.4]ANOVA
Secondary
Percentages of Participants With Seroconversion (Rabies Virus Neutralizing Antibody Concentrations Equal and Above 0.5 IU/ml) on Days 7, 14 and 42.
Percentages of participants with seroconversion (defined as rabies virus neutralizing antibody concentrations equal and above 0.5 IU/ml) on days 7, 14 and 42.
Time frame: 7 days, 14 days and 42 days
Population: Due to the Chinese registration requirements, only a subset of subjects bloodsamples were drawn and immunogenicity was evaluated. The per protocol population of this subset was analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Abbreviated Zagreb (2-1-1) | Percentages of Participants With Seroconversion (Rabies Virus Neutralizing Antibody Concentrations Equal and Above 0.5 IU/ml) on Days 7, 14 and 42. | day 7 | 10.14 percentages of participants |
| Abbreviated Zagreb (2-1-1) | Percentages of Participants With Seroconversion (Rabies Virus Neutralizing Antibody Concentrations Equal and Above 0.5 IU/ml) on Days 7, 14 and 42. | day 14 | 100 percentages of participants |
| Abbreviated Zagreb (2-1-1) | Percentages of Participants With Seroconversion (Rabies Virus Neutralizing Antibody Concentrations Equal and Above 0.5 IU/ml) on Days 7, 14 and 42. | day 42 | 100 percentages of participants |
| Conventional Essen(1-1-1-1-1) | Percentages of Participants With Seroconversion (Rabies Virus Neutralizing Antibody Concentrations Equal and Above 0.5 IU/ml) on Days 7, 14 and 42. | day 7 | 10.0 percentages of participants |
| Conventional Essen(1-1-1-1-1) | Percentages of Participants With Seroconversion (Rabies Virus Neutralizing Antibody Concentrations Equal and Above 0.5 IU/ml) on Days 7, 14 and 42. | day 14 | 97.14 percentages of participants |
| Conventional Essen(1-1-1-1-1) | Percentages of Participants With Seroconversion (Rabies Virus Neutralizing Antibody Concentrations Equal and Above 0.5 IU/ml) on Days 7, 14 and 42. | day 42 | 100 percentages of participants |
Secondary
Rabies Virus Neutralizing Antibody Concentrations on Day 7 and Day 42.
Rabies virus neutralizing antibody concentrations the abbreviated Zagreb regimen compared with the conventional Essen regimen. Results are presented on log2 scale. For results on original geometric (multiplicative) scale please raise numbers to the basis of 2.
Time frame: 7 days and 42 days
Population: Due to the Chinese registration requirements, only a subset of subjects bloodsamples were drawn and immunogenicity was evaluated. The per protocol population of this subset was analyzed.
| Arm | Measure | Group | Value (LOG_MEAN) |
|---|---|---|---|
| Abbreviated Zagreb (2-1-1) | Rabies Virus Neutralizing Antibody Concentrations on Day 7 and Day 42. | day 7 results | -3.23 IU/ml |
| Abbreviated Zagreb (2-1-1) | Rabies Virus Neutralizing Antibody Concentrations on Day 7 and Day 42. | day 42 results | 4.25 IU/ml |
| Conventional Essen(1-1-1-1-1) | Rabies Virus Neutralizing Antibody Concentrations on Day 7 and Day 42. | day 7 results | -3.02 IU/ml |
| Conventional Essen(1-1-1-1-1) | Rabies Virus Neutralizing Antibody Concentrations on Day 7 and Day 42. | day 42 results | 4.32 IU/ml |
95% CI: [-0.77, 0.35]ANOVA
95% CI: [-0.72, 0.58]ANOVA