Trial Outcomes & Findings for Safety and Immunogenicity (Non-inferiority) of a Purified Chick Embryo Cell Vaccine Vaccine Administered in Two Different Schedules (Conventional Versus Abbreviated Schedule) (NCT NCT00825305)

Last Updated: 2011-12-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

825 participants

Primary outcome timeframe

14 days

Results posted on

2011-12-13

Participant Flow

Study participants were enrolled in November 2008 at 1 center in China.

All enrolled subjects were randomized, but one subject in the Zagreb (2-1-1) group was not vaccinated.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	550	275
Overall Study COMPLETED	533	252
Overall Study NOT COMPLETED	17	23

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Adverse Event	1	1
Overall Study Withdrawal by Subject	6	12
Overall Study Inappropriate inclusion	1	0
Overall Study Protocol Violation	9	9
Overall Study Can not be classified	0	1

Baseline Characteristics

Safety and Immunogenicity (Non-inferiority) of a Purified Chick Embryo Cell Vaccine Vaccine Administered in Two Different Schedules (Conventional Versus Abbreviated Schedule)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abbreviated Zagreb (2-1-1) n=549 Participants Abbreviated Zagreb vaccination schedule with 2 vaccinations at day 0, 1 vaccination at day 7 and 1 vaccination at day 21.	Conventional Essen(1-1-1-1-1) n=275 Participants Conventional Essen schedule with 1 vaccination on day 0, day 3, day 7, day 14 and day 28, respectively.	Total n=824 Participants Total of all reporting groups
Age Continuous	38.2 years STANDARD_DEVIATION 7.14 • n=5 Participants	39.33 years STANDARD_DEVIATION 6.93 • n=7 Participants	38.58 years STANDARD_DEVIATION 7.09 • n=5 Participants
Sex: Female, Male Female	323 Participants n=5 Participants	154 Participants n=7 Participants	477 Participants n=5 Participants
Sex: Female, Male Male	226 Participants n=5 Participants	121 Participants n=7 Participants	347 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Abbreviated Zagreb (2-1-1) n=69 Participants Abbreviated Zagreb vaccination schedule with 2 vaccinations at day 0, 1 vaccination at day 7 and 1 vaccination at day 21.	Conventional Essen(1-1-1-1-1) n=70 Participants Conventional Essen schedule with 1 vaccination on day 0, day 3, day 7, day 14 and day 28, respectively.
Rabies Virus Neutralizing Antibody Concentrations on Day 14.	3.1 IU/mL Interval 2.73 to 3.47	3.3 IU/mL Interval 2.82 to 3.79

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Abbreviated Zagreb (2-1-1) n=549 Participants Abbreviated Zagreb vaccination schedule with 2 vaccinations at day 0, 1 vaccination at day 7 and 1 vaccination at day 21.	Conventional Essen(1-1-1-1-1) n=275 Participants Conventional Essen schedule with 1 vaccination on day 0, day 3, day 7, day 14 and day 28, respectively.
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Any local reaction	483 participants	241 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Erythema	37 participants	18 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Swelling	42 participants	38 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Pain	475 participants	236 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Any systemic reaction	177 participants	103 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Chills	21 participants	8 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Malaise	35 participants	17 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Headache	91 participants	49 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Nausea	28 participants	24 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Myalgia	29 participants	23 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Arthralgia	13 participants	13 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Fatigue	61 participants	34 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Rash	3 participants	33 participants
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination Fever ≥37.1°C	124 participants	68 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Abbreviated Zagreb (2-1-1) n=69 Participants Abbreviated Zagreb vaccination schedule with 2 vaccinations at day 0, 1 vaccination at day 7 and 1 vaccination at day 21.	Conventional Essen(1-1-1-1-1) n=70 Participants Conventional Essen schedule with 1 vaccination on day 0, day 3, day 7, day 14 and day 28, respectively.
Rabies Virus Neutralizing Antibody Concentrations on Day 7 and Day 42. day 7 results	-3.23 IU/ml Interval -3.6 to -2.86	-3.02 IU/ml Interval -3.45 to -2.59
Rabies Virus Neutralizing Antibody Concentrations on Day 7 and Day 42. day 42 results	4.25 IU/ml Interval 3.8 to 4.7	4.32 IU/ml Interval 3.84 to 4.79

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Abbreviated Zagreb (2-1-1) n=69 Participants Abbreviated Zagreb vaccination schedule with 2 vaccinations at day 0, 1 vaccination at day 7 and 1 vaccination at day 21.	Conventional Essen(1-1-1-1-1) n=70 Participants Conventional Essen schedule with 1 vaccination on day 0, day 3, day 7, day 14 and day 28, respectively.
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 Interval 4.18 to 19.79	10.0 percentages of participants Interval 4.12 to 19.52
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 Interval 94.79 to 100.0	97.14 percentages of participants Interval 90.19 to 99.66
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 Interval 94.79 to 100.0	100 percentages of participants Interval 94.87 to 100.0

Adverse Events

Abbreviated Zagreb (2-1-1)

Serious events: 0 serious events

Other events: 52 other events

Deaths: 0 deaths

Conventional Essen(1-1-1-1-1)

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Abbreviated Zagreb (2-1-1) n=549 participants at risk Abbreviated Zagreb vaccination schedule with 2 vaccinations at day 0, 1 vaccination at day 7 and 1 vaccination at day 21.	Conventional Essen(1-1-1-1-1) n=275 participants at risk Conventional Essen schedule with 1 vaccination on day 0, day 3, day 7, day 14 and day 28, respectively.
Musculoskeletal and connective tissue disorders Injury of soft tissue in the leg and shoulder	0.00% 0/549 • Any unsolicited adverse events were collected for 7 days after each vaccination, all serious adverse events were collected throughout the whole study period (beyond individual study participation, from 12 Nov 2008 to 12 Jan 2009). Subjects were instructed to report on a daily basis any adverse events and record them on a diary card.	0.36% 1/275 • Number of events 1 • Any unsolicited adverse events were collected for 7 days after each vaccination, all serious adverse events were collected throughout the whole study period (beyond individual study participation, from 12 Nov 2008 to 12 Jan 2009). Subjects were instructed to report on a daily basis any adverse events and record them on a diary card.

Other adverse events

Other adverse events
Measure	Abbreviated Zagreb (2-1-1) n=549 participants at risk Abbreviated Zagreb vaccination schedule with 2 vaccinations at day 0, 1 vaccination at day 7 and 1 vaccination at day 21.	Conventional Essen(1-1-1-1-1) n=275 participants at risk Conventional Essen schedule with 1 vaccination on day 0, day 3, day 7, day 14 and day 28, respectively.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	9.5% 52/549 • Number of events 52 • Any unsolicited adverse events were collected for 7 days after each vaccination, all serious adverse events were collected throughout the whole study period (beyond individual study participation, from 12 Nov 2008 to 12 Jan 2009). Subjects were instructed to report on a daily basis any adverse events and record them on a diary card.	9.5% 26/275 • Number of events 26 • Any unsolicited adverse events were collected for 7 days after each vaccination, all serious adverse events were collected throughout the whole study period (beyond individual study participation, from 12 Nov 2008 to 12 Jan 2009). Subjects were instructed to report on a daily basis any adverse events and record them on a diary card.

Additional Information

Posting Director

Novartis Vaccines and Diagnostics

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60