Download PDF

Clinical Trial Results:
A Phase IV, Uncontrolled, Open-Label, Single-Center Study in Adolescents and Adults: Evaluation of Immunogenicity and Safety of the First Booster Vaccination With Novartis Vaccines and Diagnostics (Ex Chiron’s) TBE Vaccine for Adults in Participants of Study V48P7 and Long-Term Evaluation of Immunogenicity up to 5 Years After First Booster Vaccination.

Summary
EudraCT number	2011-003255-19
Trial protocol	CZ
Global end of trial date	07 Oct 2011

Results information
Results version number	v2
This version publication date	16 Jun 2016
First version publication date	22 Feb 2015
Other versions	v1 (removed from public view) , v3 , v4
Version creation reason	Correction of full data set e-QC of the study needed because of EudraCT system glitch and updates are required.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

V48P7E1

ISRCTN number

US NCT number

NCT00387634

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Vaccines and Diagnostics GmbH & Co. KG

Sponsor organisation address

Postfach 1630, Marburg, Germany, 35006

Public contact

Posting Director, Novartis Vaccines , RegistryContactVaccinesUS@novartis.com

Scientific contact

Posting Director, Novartis Vaccines , RegistryContactVaccinesUS@novartis.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

13 Aug 2013

Is this the analysis of the primary completion data?

Yes

Primary completion date

07 Oct 2011

Global end of trial reached?

Yes

Global end of trial date

07 Oct 2011

Was the trial ended prematurely?

Main objective of the trial

Descriptive evaluation of subjects with respect to antibody titers and percentage of subjects with neutralizing antibodies on day 0 in study V48P7E1 (ie, day of first booster vaccination after primary vaccination in study V48P7 for subjects who did not get a booster vaccination, or first blood draw for those who did receive a booster dose), on day 21 in study V48P7E1 (7 days) and year 1, 2, 3, 4, and 5 (±30 days each) after booster vaccination with Novartis Vaccines and Diagnostics (ex Chiron’s) tick borne encephalitis (TBE) vaccine for adults as measured by neutralization test ([NT]; in-house, Novartis Vaccines and Diagnostics).

Protection of trial subjects

This study was performed with the ethical principles that have their origin in the Declaration of Helsinki, that are consistent with GCP according to International Conference on Harmonisation (ICH) guidelines, the applicable regulatory requirements(s) for the country in which the study was conducted, and applicable standard operating procedures (SOPs).

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Sep 2006

Long term follow-up planned

Yes

Long term follow-up rationale

Efficacy

Long term follow-up duration

5 Years

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Czech Republic: 323

Worldwide total number of subjects

323

EEA total number of subjects

323

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

293

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Subjects were enrolled in 1 site in Czech Republic.

Screening details

All the enrolled subjects were included in the trial.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

TBE_R

Arm description

Subjects received First booster vaccine at 3 years after the completion of the primary vaccination series of study V48P7. Primary vaccination: Rapid (R) schedule group- all 3 vaccinations were given within 3 weeks, with an interval of 1 week between the first and second vaccination and an interval of 2 weeks between the second and third vaccination (ie, on day 0, day 7, day 21 of study V48P7).

Arm type

Experimental

Investigational medicinal product name

TBE vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 ml

TBE_R_B

Arm description

Subjects received the first booster between study V48P7 and V48P7E1 at 12 to 18 months after the completion of the primary vaccination series of study V48P7. Primary vaccination: Rapid (R) schedule group- all 3 vaccinations were given within 3 weeks, with an interval of 1 week between the first and second vaccination and an interval of 2 weeks between the second and third vaccination (ie, on day 0, day 7, day 21 of study V48P7).

Arm type

No intervention

Investigational medicinal product name

TBE vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 ml

TBE_C

Arm description

Subjects received First booster vaccine at 3 years after the completion of the primary vaccination series of study V48P7. Primary vaccination Conventional schedule group-consisted of 3 vaccinations with an interval of 1 month between the first and second vaccination and an interval of 10 months to 12 months between the second and third vaccination (ie, on day 0, day 28, day 300 of study V48P7).

Arm type

Experimental

Investigational medicinal product name

TBE vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 ml

TBE_MC

Arm description

Subjects received First booster vaccine at 3 years after the completion of the primary vaccination series of study V48P7. Primary vaccination Modified conventional (MC) schedule group-TBE vaccine was given with a reduced interval between first and second vaccination; ie, from 28 days to 21 days (ie, vaccinations on day 0, day 21, day 300 of study V48P7).

Arm type

Experimental

Investigational medicinal product name

TBE vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 ml

TBE_AC

Arm description

Subjects received First booster vaccine at 3 years after the completion of the primary vaccination series of study V48P7. Primary vaccination Accelerated conventional (AC) schedule group-TBE vaccine was given by means of an even more reduced interval between the first and second vaccination; ie, from 28 days to 14 days (ie, vaccinations on day 0, day 14, and day 300 of study V48P7).

Arm type

Experimental

Investigational medicinal product name

TBE vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 ml

Number of subjects in period 1	TBE_R	TBE_R_B	TBE_C	TBE_MC	TBE_AC
Started	9	40	55	110	109
Completed	9	39	52	107	106
Not completed	0	1	3	3	3
Death	-	1	1	-	2
Lost to follow-up	-	-	1	1	-
Protocol deviation	-	-	1	2	1

Baseline characteristics

Top of page

Reporting group title

TBE_R

Reporting group description

Reporting group title

TBE_R_B

Reporting group description

Reporting group title

TBE_C

Reporting group description

Reporting group title

TBE_MC

Reporting group description

Reporting group title

TBE_AC

Reporting group description

Reporting group values	TBE_R	TBE_R_B	TBE_C	TBE_MC	TBE_AC	Total
Number of subjects	9	40	55	110	109	323
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	31.6 ( 9.2 )	38.1 ( 16.4 )	36.3 ( 14.5 )	37.5 ( 14.3 )	37.1 ( 14.4 )	-
Gender categorical
Units: Subjects
Female	5	19	35	63	58	180
Male	4	21	20	47	51	143

Subject analysis set title

All enrolled set

Subject analysis set type

Per protocol

Subject analysis set description

The enrolled population contained all subjects enrolled in the study, ie, with a record in DEMOG panel. This population was used for the analysis of demographics, concomitant medications, medical history and all subject listings.

Subject analysis set title

Safety Population

Subject analysis set type

Safety analysis

Subject analysis set description

The safety population included all subjects who received a booster vaccination on day 0 (V48P7E1) excluding TBE_R_B group and provided postvaccination safety data.

Subject analysis set title

Full Analysis Set (FAS) Immunogenecity

Subject analysis set type

Full analysis

Subject analysis set description

All subjects who: ▫ were admitted to the study, irrespective whether they received study vaccination or not; ▫ provided at least one evaluable serum sample

Subject analysis set title

Per-Protocol (PP) Population, Immunogenicity

Subject analysis set type

Per protocol

Subject analysis set description

The PPS comprised all subjects who: ▫ received the relevant booster vaccination correctly or had completed the rapid schedule and had already received a booster vaccination prior to admission into the present study; ▫ provided evaluable serum samples at the relevant time points; ▫ presented no major violations regarding concomitant medication/concomitant disease; ▫ had no major violations of inclusion/exclusion criteria. Specifically, subjects meeting the following criteria were excluded from the PPS: ▫ subjects who received another vaccine within 4 weeks after the administration of the study vaccine*; ▫ subjects treated with immunoglobulins, whole blood or plasma derivates up to 4 weeks after administration of study vaccine subjects treated with immunosuppressants or systemic corticosteroids during the study period, except short term use of topic corticosteroids or low-dose systemic use (e.g.,up to 10 mg of prednisolone for up to 14 days). Subjects meeting the following crite

Subject analysis sets values	All enrolled set	Safety Population	Full Analysis Set (FAS) Immunogenecity	Per-Protocol (PP) Population, Immunogenicity
Number of subjects	323	278	323	289
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	37.1 ( 14.5 )	( )	( )	( )
Gender categorical
Units: Subjects
Female	180
Male	143

End points

Top of page

Reporting group title

TBE_R

Reporting group description

Reporting group title

TBE_R_B

Reporting group description

Reporting group title

TBE_C

Reporting group description

Reporting group title

TBE_MC

Reporting group description

Reporting group title

TBE_AC

Reporting group description

Subject analysis set title

All enrolled set

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Safety Population

Subject analysis set type

Safety analysis

Subject analysis set description

The safety population included all subjects who received a booster vaccination on day 0 (V48P7E1) excluding TBE_R_B group and provided postvaccination safety data.

Subject analysis set title

Full Analysis Set (FAS) Immunogenecity

Subject analysis set type

Full analysis

Subject analysis set description

All subjects who: ▫ were admitted to the study, irrespective whether they received study vaccination or not; ▫ provided at least one evaluable serum sample

Subject analysis set title

Per-Protocol (PP) Population, Immunogenicity

Subject analysis set type

Per protocol

Subject analysis set description

Primary: 1. Percentage of Subjects With Antibody Titers ≥2 as Measured by NT.

Top of page

End point title

1. Percentage of Subjects With Antibody Titers ≥2 as Measured by NT. ^[1]

End point description

Immunogenicity was measured in terms of the Percentage of Subjects With Antibody Titers ≥2 as Measured by Neutralization-test (NT). Data are reported based on the Per Protocol Set (PPS).

End point type

Primary

End point timeframe

Year 5

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: no statistical analyses reported for this endpoint.

End point values	TBE_R	TBE_R_B	TBE_C	TBE_MC	TBE_AC
Number of subjects analysed	8	37	51	101	101
Units: Percentage of subjects
number (confidence interval 95%)
Day 0	88 (47 to 100)	100 (91 to 100)	100 (93 to 100)	99 (95 to 100)	100 (96 to 100)
Day 21 (N=8,0,51,101,100)	100 (63 to 100)	0 (0 to 0)	100 (93 to 100)	100 (96 to 100)	100 (96 to 100)
Year 1 (N=8,35,50,100,101)	100 (63 to 100)	100 (90 to 100)	100 (93 to 100)	100 (96 to 100)	100 (96 to 100)
Year 2 (N=8,35,51,99,100)	100 (63 to 100)	100 (90 to 100)	100 (93 to 100)	100 (96 to 100)	100 (96 to 100)
Year 3 (N=8,35,49,100,100)	100 (63 to 100)	97 (85 to 100)	100 (93 to 100)	100 (96 to 100)	100 (96 to 100)
Year 4 (N=7,34,48,99,100)	100 (59 to 100)	100 (90 to 100)	100 (93 to 100)	100 (96 to 100)	100 (96 to 100)
Year 5 (N=8,36,48,98,99)	100 (63 to 100)	100 (90 to 100)	100 (93 to 100)	100 (96 to 100)	100 (96 to 100)

No statistical analyses for this end point

Primary: 2. Percentage of Subjects With Antibody Titers ≥10 as Measured by NT.

Top of page

End point title

2. Percentage of Subjects With Antibody Titers ≥10 as Measured by NT. ^[2]

End point description

Immunogenicity was measured in terms of the Percentage of Subjects With Antibody Titers ≥10 as Measured by NT. Data are reported based on the PPS.

End point type

Primary

End point timeframe

Year 5

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: no statistical analyses reported for this endpoint.

End point values	TBE_R	TBE_R_B	TBE_C	TBE_MC	TBE_AC
Number of subjects analysed	8	37	51	101	101
Units: Percentage of Subjects
number (confidence interval 95%)
Day 0	75 (35 to 97)	97 (86 to 100)	98 (90 to 100)	97 (92 to 99)	99 (95 to 100)
Day 21 (N=8,0,51,101,100)	100 (63 to 100)	0 (0 to 0)	100 (93 to 100)	100 (96 to 100)	100 (96 to 100)
Year 1 (N=8,35,50,100,101)	100 (63 to 100)	97 (85 to 100)	100 (93 to 100)	100 (96 to 100)	100 (96 to 100)
Year 2 (N=8,35,51,99,100)	100 (63 to 100)	97 (85 to 100)	100 (93 to 100)	99 (95 to 100)	100 (96 to 100)
Year 3 (N=8,35,49,100,100)	100 (63 to 100)	97 (85 to 100)	100 (93 to 100)	95 (89 to 98)	100 (96 to 100)
Year 4 (N=7,34,48,99,100)	100 (59 to 100)	94 (80 to 99)	100 (93 to 100)	97 (91 to 99)	100 (96 to 100)
Year 5 (N=8,36,48,98,99)	100 (63 to 100)	97 (85 to 100)	100 (93 to 100)	98 (93 to 100)	100 (96 to 100)

No statistical analyses for this end point

Primary: 3. Geometric Mean Antibody Titers (GMT) as Measured by NT.

Top of page

End point title

3. Geometric Mean Antibody Titers (GMT) as Measured by NT. ^[3]

End point description

Immunogenicity was measured in terms of the Geometric Mean Antibody Titers (GMT) as Measured by NT. Data are reported based on the PPS.

End point type

Primary

End point timeframe

Year 5

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: no statistical analyses reported for this endpoint.

End point values	TBE_R	TBE_R_B	TBE_C	TBE_MC	TBE_AC
Number of subjects analysed	8	37	51	101	101
Units: Titers
geometric mean (confidence interval 95%)
Day 0	67 (22 to 201)	395 (236 to 658)	232 (150 to 359)	206 (151 to 281)	237 (174 to 323)
Day 21 (N=8,0,51,101,100)	1476 (646 to 3373)	0 (0 to 0)	1182 (852 to 1640)	1024 (812 to 1293)	1059 (838 to 1338)
Year 1 (N=8,35,50,100,101)	378 (152 to 936)	234 (152 to 362)	240 (167 to 345)	249 (193 to 322)	246 (190 to 317)
Year 2 (N=8,35,51,99,100)	370 (150 to 913)	235 (152 to 362)	229 (160 to 327)	211 (163 to 272)	232 (180 to 300)
Year 3 (N=8,35,49,100,100)	331 (121 to 910)	235 (145 to 380)	230 (153 to 346)	211 (159 to 281)	228 (171 to 303)
Year 4 (N=7,34,48,99,100)	137 (50 to 379)	192 (121 to 304)	250 (169 to 368)	208 (159 to 273)	253 (193 to 331)
Year 5 (N=8,36,48,98,99)	429 (151 to 1217)	358 (219 to 586)	300 (196 to 460)	281 (208 to 378)	305 (227 to 410)

No statistical analyses for this end point

Primary: 4. Ratios of Geometric Mean Antibody Titers (GMT) as Measured by NT.

Top of page

End point title

4. Ratios of Geometric Mean Antibody Titers (GMT) as Measured by NT. ^[4]

End point description

Immunogenicity was measured in terms of the Ratios of Geometric Mean Antibody Titers (GMT) as Measured by NT. Data are reported based on the PPS.

End point type

Primary

End point timeframe

Year 5

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: no statistical analyses reported for this endpoint.

End point values	TBE_R	TBE_R_B	TBE_C	TBE_MC	TBE_AC
Number of subjects analysed	8	37	51	101	101
Units: Ratio of GMTs
number (confidence interval 95%)
Day 21/Day 0 (N=8,0,51,101,100)	22 (11 to 45)	0 (0 to 0)	5.1 (3.85 to 6.75)	4.97 (4.07 to 6.07)	4.5 (3.68 to 5.49)
year 1/day 0 (N=8,35,50,100,101)	5.66 (2.83 to 11)	0.57 (0.41 to 0.79)	1.04 (0.79 to 1.37)	1.21 (1 to 1.48)	1.04 (0.85 to 1.26)
Year2/day 0 (N=8,35,51,99,100)	5.55 (3.09 to 9.96)	0.57 (0.43 to 0.75)	0.99 (0.78 to 1.24)	1.03 (0.87 to 1.21)	0.96 (0.82 to 1.14)
Year 3/day 0 (N=8,35,49,100,100)	4.97 (2.8 to 8.8)	0.57 (0.43 to 0.75)	1.04 (0.82 to 1.31)	1.05 (0.89 to 1.23)	0.95 (0.81 to 1.12)
Year 4/day 0 (N=7,34,48,99,100)	2.15 (0.92 to 5)	0.47 (0.32 to 0.69)	1.06 (0.77 to 1.46)	1.04 (0.83 to 1.31)	1.05 (0.84 to 1.32)
Year 5/day 0 (N=8,36,48,98,99)	6.44 (3.56 to 12)	0.88 (0.67 to 1.16)	1.28 (1 to 1.63)	1.38 (1.16 to 1.63)	1.28 (1.08 to 1.51)

No statistical analyses for this end point

Primary: 5. Geometric Mean Antibody Titers as Measured by NT for Rapid Schedule Only.

Top of page

End point title

5. Geometric Mean Antibody Titers as Measured by NT for Rapid Schedule Only. ^[5] ^[6]

End point description

Immunogenicity was measured in terms of the Geometric Mean Antibody Titers as Measured by NT for Rapid Schedule Only. Data are reported based on the PPS.

End point type

Primary

End point timeframe

Visit 6 up to visit 10 (Day 0)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: no statistical analyses reported for this endpoint.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: no statistical analyses reported for this endpoint.

End point values	TBE_R	TBE_R_B
Number of subjects analysed	8	37
Units: Titers
geometric mean (confidence interval 95%)
Visit 6	64 (27 to 152)	42 (28 to 63)
Visit 7	19 (7.76 to 45)	33 (22 to 49)
Visit 8	14 (6.29 to 30)	24 (17 to 34)
Visit 10	67 (21 to 208)	395 (232 to 670)

No statistical analyses for this end point

Primary: 6. Ratios of Geometric Mean Antibody Titers as Measured by NT for Rapid Schedule Only.

Top of page

End point title

6. Ratios of Geometric Mean Antibody Titers as Measured by NT for Rapid Schedule Only. ^[7] ^[8]

End point description

Immunogenicity was measured in terms of the ratios of the Geometric Mean Antibody Titers as Measured by NT for Rapid Schedule Only. Data are reported based on the PPS.

End point type

Primary

End point timeframe

up to Visit 10 (Day 0)

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: no statistical analyses reported for this endpoint.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: no statistical analyses reported for this endpoint.

End point values	TBE_R	TBE_R_B
Number of subjects analysed	8	37
Units: Ratio of GMTs
number (confidence interval 95%)
Visit 10: Visit 6	1.04 (0.3 to 3.57)	9.4 (5.3 to 17)
Visit 10: Visit 7	3.56 (1.26 to 10)	12 (7.46 to 20)
Visit 10: Visit 8	4.87 (1.82 to 13)	16 (10 to 26)

No statistical analyses for this end point

Primary: 7. Geometric Mean Antibody Titers as Measured by NT for Conventional Schedules.

Top of page

End point title

7. Geometric Mean Antibody Titers as Measured by NT for Conventional Schedules. ^[9] ^[10]

End point description

Immunogenicity was measured in terms of the Geometric Mean Antibody Titers as Measured by NT for Conventional Schedules. Data are reported based on the PPS.

End point type

Primary

End point timeframe

up to visit 10 (Day 0)

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: no statistical analyses reported for this endpoint.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: no statistical analyses reported for this endpoint.

End point values	TBE_C	TBE_MC	TBE_AC
Number of subjects analysed	51	101	101
Units: Titers
geometric mean (confidence interval 95%)
Visit 9	1131 (770 to 1660)	1133 (862 to 1489)	1143 (870 to 1501)
Visit 10	232 (150 to 359)	206 (151 to 281)	237 (174 to 323)

No statistical analyses for this end point

Primary: 8. Ratios of the Geometric Mean Antibody Titers as Measured by NT for Conventional Schedules.

Top of page

End point title

8. Ratios of the Geometric Mean Antibody Titers as Measured by NT for Conventional Schedules. ^[11] ^[12]

End point description

Immunogenicity was measured in terms of the ratios of the Geometric Mean Antibody Titers as Measured by NT for Conventional Schedules. Data are reported based on the PPS.

End point type

Primary

End point timeframe

up to Visit 10 (Day 0)

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: no statistical analyses reported for this endpoint.
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: no statistical analyses reported for this endpoint.

End point values	TBE_C	TBE_MC	TBE_AC
Number of subjects analysed	51	101	101
Units: Ratio of GMTs
number (confidence interval 95%)
Visit 10/visit 9	0.21 (0.16 to 0.26)	0.18 (0.15 to 0.21)	0.21 (0.18 to 0.24)

No statistical analyses for this end point

Secondary: 9. Number of subjects with solicited local and solicited systemic AEs

Top of page

End point title

9. Number of subjects with solicited local and solicited systemic AEs ^[13]

End point description

Safety was assessed in terms of the Number of subjects with solicited local and solicited systemic AEs up to 3 days after booster vaccination.

End point type

Secondary

End point timeframe

4 days (up to day 3)

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Safety analyses were run descriptively.

End point values	TBE_R	TBE_C	TBE_MC	TBE_AC
Number of subjects analysed	9	55	108	106
Units: Subjects
Pain_Classification A	7	35	59	52
Erythema (mm)_Classification A	1	3	9	9
Swelling (mm)_Classification A	0	4	7	6
Pain_Classification B	7	35	59	52
Erythema (mm)_Classification B	0	1	4	1
Swelling (mm)_Classification B	0	3	6	1
Nausea	1	2	3	4
Malaise	1	3	8	7
Myalgia	3	12	18	13
Arthralgia	1	3	7	3
Headache	2	8	12	17

No statistical analyses for this end point

Secondary: 10. Number of Subjects with unsolicited AEs.

Top of page

End point title

10. Number of Subjects with unsolicited AEs. ^[14]

End point description

Safety was assessed in terms of the number of subjects with unsolicited Adverse Events from Day 0 up to Day 21.

End point type

Secondary

End point timeframe

Day 0 up to day 21.

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Safety analyses were run descriptively.

End point values	TBE_R	TBE_C	TBE_MC	TBE_AC
Number of subjects analysed	9	55	108	106
Units: Partecipants
Any Adverse Events	1	9	12	14
At least possibly related AEs	1	3	5	3
Serious AEs	0	3	5	7
At least possibly related SAEs	0	0	0	0
Deaths	0	1	0	2

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Day 0 through year 5.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

TBE_R

Reporting group description

Reporting group title

TBE_C

Reporting group description

Reporting group title

TBE_AC

Reporting group description

Reporting group title

TBE_MC

Reporting group description

Serious adverse events	TBE_R	TBE_C	TBE_AC	TBE_MC
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 9 (0.00%)	3 / 55 (5.45%)	7 / 106 (6.60%)	5 / 108 (4.63%)
number of deaths (all causes)	0	1	2	0
number of deaths resulting from adverse events	0		2	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
subjects affected / exposed	0 / 9 (0.00%)	1 / 55 (1.82%)	0 / 106 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Glioblastoma
subjects affected / exposed	0 / 9 (0.00%)	1 / 55 (1.82%)	1 / 106 (0.94%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0
Malignant melanoma
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	1 / 106 (0.94%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle Fracture
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	0 / 106 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	0 / 106 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Patella Fracture
subjects affected / exposed	0 / 9 (0.00%)	1 / 55 (1.82%)	0 / 106 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal Fracture
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	1 / 106 (0.94%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thoracic vertebral fracture
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	1 / 106 (0.94%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Trisomy 21
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	0 / 106 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina Pectoris
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	0 / 106 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial Infarction
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	1 / 106 (0.94%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
Supraventricular Tachycardia
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	0 / 106 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Abortion induced
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	0 / 106 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Peroneal Nerve Palsy
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	1 / 106 (0.94%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	0 / 106 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	1 / 106 (0.94%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	0 / 9 (0.00%)	0 / 55 (0.00%)	1 / 106 (0.94%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	TBE_R	TBE_C	TBE_AC	TBE_MC
Total subjects affected by non serious adverse events
subjects affected / exposed	7 / 9 (77.78%)	40 / 55 (72.73%)	62 / 106 (58.49%)	69 / 108 (63.89%)
Nervous system disorders
Headache
subjects affected / exposed	2 / 9 (22.22%)	8 / 55 (14.55%)	17 / 106 (16.04%)	12 / 108 (11.11%)
occurrences all number	3	10	19	14
General disorders and administration site conditions
Injection site erythema
subjects affected / exposed	1 / 9 (11.11%)	3 / 55 (5.45%)	9 / 106 (8.49%)	9 / 108 (8.33%)
occurrences all number	1	3	9	9
Injection site swelling
subjects affected / exposed	0 / 9 (0.00%)	4 / 55 (7.27%)	6 / 106 (5.66%)	7 / 108 (6.48%)
occurrences all number	0	4	6	7
Injectino site pain
subjects affected / exposed	7 / 9 (77.78%)	35 / 55 (63.64%)	52 / 106 (49.06%)	59 / 108 (54.63%)
occurrences all number	7	35	53	60
Malaise
subjects affected / exposed	1 / 9 (11.11%)	3 / 55 (5.45%)	7 / 106 (6.60%)	8 / 108 (7.41%)
occurrences all number	1	4	8	8
Pyrexia
subjects affected / exposed	1 / 9 (11.11%)	2 / 55 (3.64%)	1 / 106 (0.94%)	3 / 108 (2.78%)
occurrences all number	1	2	1	3
Gastrointestinal disorders
Nausea
subjects affected / exposed	1 / 9 (11.11%)	2 / 55 (3.64%)	4 / 106 (3.77%)	3 / 108 (2.78%)
occurrences all number	1	3	5	3
Musculoskeletal and connective tissue disorders
Athralgia
subjects affected / exposed	1 / 9 (11.11%)	3 / 55 (5.45%)	3 / 106 (2.83%)	7 / 108 (6.48%)
occurrences all number	1	3	3	9
Myalgia
subjects affected / exposed	3 / 9 (33.33%)	12 / 55 (21.82%)	13 / 106 (12.26%)	18 / 108 (16.67%)
occurrences all number	3	14	13	19

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

15 Feb 2008

slight revision of wording regarding points of time of blood withdrawal; adjustment related to ELISA tests (ie, TBE antibody titers were to be determined by Neutralization Test only).Specification of SAE reporting procedure

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/24950352

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 1. Percentage of Subjects With Antibody Titers ≥2 as Measured by NT.

Primary: 1. Percentage of Subjects With Antibody Titers ≥2 as Measured by NT.

Primary: 2. Percentage of Subjects With Antibody Titers ≥10 as Measured by NT.

Primary: 2. Percentage of Subjects With Antibody Titers ≥10 as Measured by NT.

Primary: 3. Geometric Mean Antibody Titers (GMT) as Measured by NT.

Primary: 3. Geometric Mean Antibody Titers (GMT) as Measured by NT.

Primary: 4. Ratios of Geometric Mean Antibody Titers (GMT) as Measured by NT.

Primary: 4. Ratios of Geometric Mean Antibody Titers (GMT) as Measured by NT.

Primary: 5. Geometric Mean Antibody Titers as Measured by NT for Rapid Schedule Only.

Primary: 5. Geometric Mean Antibody Titers as Measured by NT for Rapid Schedule Only.

Primary: 6. Ratios of Geometric Mean Antibody Titers as Measured by NT for Rapid Schedule Only.

Primary: 6. Ratios of Geometric Mean Antibody Titers as Measured by NT for Rapid Schedule Only.

Primary: 7. Geometric Mean Antibody Titers as Measured by NT for Conventional Schedules.

Primary: 7. Geometric Mean Antibody Titers as Measured by NT for Conventional Schedules.

Primary: 8. Ratios of the Geometric Mean Antibody Titers as Measured by NT for Conventional Schedules.

Primary: 8. Ratios of the Geometric Mean Antibody Titers as Measured by NT for Conventional Schedules.

Secondary: 9. Number of subjects with solicited local and solicited systemic AEs

Secondary: 9. Number of subjects with solicited local and solicited systemic AEs

Secondary: 10. Number of Subjects with unsolicited AEs.

Secondary: 10. Number of Subjects with unsolicited AEs.

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA