Long Term Persistence and Effect of a Booster Dose of the Japanese Encephalitis Vaccine IC51

• Sponsor: Valneva Austria GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00595270
• Collaborator: (none)
• Enrollment: 349
• Arm: 1
• Duration (Months): 42

Study Details

Study Description

Brief Summary

The study investigates the long term persistence the Japanese encephalitis vaccine IC51 and the need of a booster dose

Condition or Disease	Intervention/Treatment	Phase
Japanese Encephalitis	Biological: IC51	Phase 3

Detailed Description

This is an open label, non-randomized multi-center phase 3 follow-up study. All volunteers having completed trial IC51-304 (NCT00595790) will be enrolled into this trial at 2 sites

Study Design

• Study Type: Interventional
• Actual Enrollment: 349 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Long Term Persistence and Effect of a Booster Dose of the Japanese Encephalitis Vaccine IC51
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Sep 1, 2007
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Other: IC51 In study IC51-305, subjects who had received IC51 in study IC51-304 were tested for seroconversion 6 months after the first vaccination. Subjects who had protective titers were again tested for persistence of immunity at 12 months after the first immunization,whereas subjects who had titers below the seroconversion threshold by Month 6 received a booster dose of 1x6 mcg IC51 at Month 11. Their immune response was also assessed at Month 12. Thereafter, subjects who had no protective titer by Month 12 received a booster dose of 1x6 mcg IC51 at Month 23, regardless of prior treatment; and neutralizing antibody titers were reassessed at Month 24. Subjects who had protective titers at month 12 did not receive a booster at Month 23, and their neutralizing antibody titer was also assessed at Month 24.

Biological: IC51; Other Names: Japanese Encephalitis purified inactivated vaccine

Outcome Measures

Primary Outcome Measures

1. Long Term Immunogenicity of IC51 Vaccine 24 Months After the Primary Vaccination [- 24 months]

   Seroprotection rate (SPR) (anti-JEV neutralizing antibody titer ≥ 1:10) 24 months (M24) after the primary vaccination - imputed; Persistence of immunogenicity (SPR) at M24 defined as: pos. (positive) (persistent): Subjects with a non-missing, pos. seroconversion at D56 (Study IC51-304) and without booster at M11 or M23 and with non-missing, seroprotection (SP) pos. PRNT50 at M6 or M12 and with non-missing, SP pos. PRNT50 at M24 neg. (negative) (non-persistent): Subjects with missing or neg. seroconversion at D56 (Study IC51-304) or booster at M11 or at M23, or non-missing, SP neg. PRNT50 at M6 or M12 or missing PRNT50 at both M6 and M12 or missing or SP neg. PRNT50 (serum dilution giving 50% reduction in plaques in a Plaque Reduction Neutralization Test) at M24

Secondary Outcome Measures

1. SPR 24 Months After the Primary Vaccination (Observed) [24 months]

   Persistence of immunogenicity (SPR) at M24 (observed) defined as : positive (persistent): Subjects with a non-missing, positive seroconversion at D56 (Study IC51-304), and who did not receive a booster dose at Visit 2 (M11) or Visit 4 (M23), and with a non-missing, SP positive PRNT50 result at Visit 1 (M6) or Visit 3 (M12), and with a non-missing, SP positive PRNT50 result at Visit 5 (M24) negative (non-persistent): Subjects with missing or negative seroconversion at D56 (Study IC51-304), or who did receive a booster dose at Visit 2 (M11) or at Visit 4 (M23), or with a non-missing, SP negative PRNT50 result at Visit 1 (M6) or Visit 3 (M12), or with a missing PRNT50 result at both Visit 1 (M6) and Visit 3 (M12), or with a non-missing, SP negative PRNT50 result at Visit 5 (M24)

2. Persistent and Actual SPR 6, 12 and 24 Months After Primary Vaccination [- 24 months]

3. Persistent and Actual GMT 6, 12 and 24 Months After Primary Vaccination [24 months]

4. SCR 1 Month After the Booster Doses [1 month]

5. GMT 1month After Booster Doses [1 month]

6. Safety Profile of IC51 [study duration]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• At least 18 years of age

• Written informed consent obtained prior to study entry

• Subjects correctly included in and having completed study IC51-304 according to the protocol.

Exclusion Criteria:

• Use of any other investigational or non-registered drug or vaccine in addition to the study vaccine during the study period

• Immunodeficiency including post-organ-transplantation or immunosuppressive therapy

• Pregnancy, lactation or unreliable contraception in female subjects

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Valneva Austria GmbH

Investigators

• Study Director: Susanne Eder, Valneva Austria GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Valneva Austria GmbH
• ClinicalTrials.gov Identifier: NCT00595270
• Other Study ID Numbers: IC51-305
• First Posted: Jan 16, 2008
• Last Update Posted: Mar 7, 2014
• Last Verified: Feb 1, 2014

• Additional relevant MeSH terms: Encephalitis, Japanese; Encephalitis; Vaccines

Study Results

Participant Flow

Arm/Group Title	IC51 2 x 6 µg	IC51 1 x 12 µg	IC51 1 x 6 µg
Arm/Group Description	treatment group in preceeding study IC51-304	treatment group in preceeding study IC51-304	treatment group in preceeding study IC51-304
Period Title: Overall Study
STARTED	116	117	116
COMPLETED	110	107	108
NOT COMPLETED	6	10	8

Baseline Characteristics

Arm/Group Title	IC51 2 x 6 µg	IC51 1 x 12 µg	IC51 1 x 6 µg	Total
Arm/Group Description	treatment group in preceeding study IC51-304	treatment group in preceeding study IC51-304	treatment group in preceeding study IC51-304	Total of all reporting groups
Overall Participants	116	117	116	349
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	109 94%	108 92.3%	106 91.4%	323 92.6%
>=65 years	7 6%	9 7.7%	10 8.6%	26 7.4%
Sex: Female, Male (Count of Participants)
Female	67 57.8%	60 51.3%	57 49.1%	184 52.7%
Male	49 42.2%	57 48.7%	59 50.9%	165 47.3%
Region of Enrollment (participants) [Number]
Europe	116 100%	117 100%	116 100%	349 100%

Outcome Measures

1. Primary Outcome

Title	Long Term Immunogenicity of IC51 Vaccine 24 Months After the Primary Vaccination
Description	Seroprotection rate (SPR) (anti-JEV neutralizing antibody titer ≥ 1:10) 24 months (M24) after the primary vaccination - imputed; Persistence of immunogenicity (SPR) at M24 defined as: pos. (positive) (persistent): Subjects with a non-missing, pos. seroconversion at D56 (Study IC51-304) and without booster at M11 or M23 and with non-missing, seroprotection (SP) pos. PRNT50 at M6 or M12 and with non-missing, SP pos. PRNT50 at M24 neg. (negative) (non-persistent): Subjects with missing or neg. seroconversion at D56 (Study IC51-304) or booster at M11 or at M23, or non-missing, SP neg. PRNT50 at M6 or M12 or missing PRNT50 at both M6 and M12 or missing or SP neg. PRNT50 (serum dilution giving 50% reduction in plaques in a Plaque Reduction Neutralization Test) at M24
Time Frame	- 24 months

Outcome Measure Data

Analysis Population Description

ITT (Intent-To-Treat) Population: included all subjects rolled over from study IC51-304; analyzed according to treatment to which they were randomized in IC51-304

Arm/Group Title	IC51 2 x 6 µg	IC51 1 x 12 µg	IC51 1 x 6 µg
Arm/Group Description	treatment group in preceeding study IC51-304	treatment group in preceeding study IC51-304	treatment group in preceeding study IC51-304
Measure Participants	116	117	116
Number (95% Confidence Interval) [percentage of participants]	56 48.3%	7 6%	5 4.3%

2. Secondary Outcome

Title	SPR 24 Months After the Primary Vaccination (Observed)
Description	Persistence of immunogenicity (SPR) at M24 (observed) defined as : positive (persistent): Subjects with a non-missing, positive seroconversion at D56 (Study IC51-304), and who did not receive a booster dose at Visit 2 (M11) or Visit 4 (M23), and with a non-missing, SP positive PRNT50 result at Visit 1 (M6) or Visit 3 (M12), and with a non-missing, SP positive PRNT50 result at Visit 5 (M24) negative (non-persistent): Subjects with missing or negative seroconversion at D56 (Study IC51-304), or who did receive a booster dose at Visit 2 (M11) or at Visit 4 (M23), or with a non-missing, SP negative PRNT50 result at Visit 1 (M6) or Visit 3 (M12), or with a missing PRNT50 result at both Visit 1 (M6) and Visit 3 (M12), or with a non-missing, SP negative PRNT50 result at Visit 5 (M24)
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Persistent and Actual SPR 6, 12 and 24 Months After Primary Vaccination
Time Frame	- 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Persistent and Actual GMT 6, 12 and 24 Months After Primary Vaccination
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	SCR 1 Month After the Booster Doses
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	GMT 1month After Booster Doses
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Safety Profile of IC51
Time Frame	study duration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	IC51 2 x 6 µg		IC51 1 x 12 µg		IC51 1 x 6 µg
Arm/Group Description	treatment group in preceeding study IC51-304		treatment group in preceeding study IC51-304		treatment group in preceeding study IC51-304
All Cause Mortality
	IC51 2 x 6 µg		IC51 1 x 12 µg		IC51 1 x 6 µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	IC51 2 x 6 µg		IC51 1 x 12 µg		IC51 1 x 6 µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/116 (3.4%)		4/117 (3.4%)		3/116 (2.6%)
Infections and infestations
Appendicitis	1/116 (0.9%)		0/117 (0%)		0/116 (0%)
Injury, poisoning and procedural complications
Facial Bones Fracture	0/116 (0%)		1/117 (0.9%)		0/116 (0%)
Hand Fracture	0/116 (0%)		0/117 (0%)		1/116 (0.9%)
Tendon Injury	0/116 (0%)		1/117 (0.9%)		0/116 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	0/116 (0%)		1/117 (0.9%)		0/116 (0%)
Intervertebral Disc Protrusion	1/116 (0.9%)		0/117 (0%)		0/116 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon Cancer	0/116 (0%)		0/117 (0%)		1/116 (0.9%)
Renal and urinary disorders
Urinary Incontinence	1/116 (0.9%)		0/117 (0%)		0/116 (0%)
Reproductive system and breast disorders
Uterine Prolapse	0/116 (0%)		0/117 (0%)		1/116 (0.9%)
Respiratory, thoracic and mediastinal disorders
Paranasal Sinus Discomfort	1/116 (0.9%)		0/117 (0%)		0/116 (0%)
Surgical and medical procedures
Hysterectomy	0/116 (0%)		1/117 (0.9%)		0/116 (0%)
Other (Not Including Serious) Adverse Events
	IC51 2 x 6 µg		IC51 1 x 12 µg		IC51 1 x 6 µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/116 (52.6%)		69/117 (59%)		64/116 (55.2%)
Blood and lymphatic system disorders
Anaemia	0/116 (0%)		0/117 (0%)		2/116 (1.7%)
Lymphadenopathy	2/116 (1.7%)		1/117 (0.9%)		0/116 (0%)
Gastrointestinal disorders
Diarrhoea	3/116 (2.6%)		3/117 (2.6%)		0/116 (0%)
Nausea	1/116 (0.9%)		6/117 (5.1%)		4/116 (3.4%)
Toothache	2/116 (1.7%)		1/117 (0.9%)		2/116 (1.7%)
Vomiting	2/116 (1.7%)		1/117 (0.9%)		1/116 (0.9%)
Abdominal Pain Upper	1/116 (0.9%)		2/117 (1.7%)		0/116 (0%)
General disorders
Fatique	5/116 (4.3%)		7/117 (6%)		6/116 (5.2%)
Influenza Like Ilness	7/116 (6%)		5/117 (4.3%)		6/116 (5.2%)
Induration	1/116 (0.9%)		0/117 (0%)		2/116 (1.7%)
Injection Site Pain	0/116 (0%)		2/117 (1.7%)		1/116 (0.9%)
Infections and infestations
Nasopharyngitis	12/116 (10.3%)		13/117 (11.1%)		11/116 (9.5%)
Sinusitis	3/116 (2.6%)		0/117 (0%)		1/116 (0.9%)
Herpes Zoster	1/116 (0.9%)		0/117 (0%)		2/116 (1.7%)
Lower Respiratory Tract Infection	2/116 (1.7%)		0/117 (0%)		1/116 (0.9%)
Pharyngitis	0/116 (0%)		0/117 (0%)		2/116 (1.7%)
Injury, poisoning and procedural complications
Accidental Poisoning	1/116 (0.9%)		3/117 (2.6%)		0/116 (0%)
Procedural Pain	1/116 (0.9%)		2/117 (1.7%)		0/116 (0%)
Investigations
Haematocrit Decreased	0/116 (0%)		2/117 (1.7%)		0/116 (0%)
Haemoglobin Decreased	0/116 (0%)		2/117 (1.7%)		0/116 (0%)
Red Blood Cell Count Decreased	0/116 (0%)		2/117 (1.7%)		0/116 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	3/116 (2.6%)		4/117 (3.4%)		2/116 (1.7%)
Myalgia	1/116 (0.9%)		4/117 (3.4%)		5/116 (4.3%)
Pain In Extremity	2/116 (1.7%)		0/117 (0%)		1/116 (0.9%)
Nervous system disorders
Headache	10/116 (8.6%)		12/117 (10.3%)		13/116 (11.2%)
Hypoaesthesia	2/116 (1.7%)		0/117 (0%)		0/116 (0%)
Reproductive system and breast disorders
Dysmenorrhoea	3/116 (2.6%)		1/117 (0.9%)		1/116 (0.9%)
Respiratory, thoracic and mediastinal disorders
Cough	5/116 (4.3%)		2/117 (1.7%)		2/116 (1.7%)
Pharyngolaryngeal Pain	5/116 (4.3%)		5/117 (4.3%)		3/116 (2.6%)
Rhinorrhoea	1/116 (0.9%)		2/117 (1.7%)		2/116 (1.7%)
Nasal Congestion	0/116 (0%)		2/117 (1.7%)		0/116 (0%)
Sinus Congestion	0/116 (0%)		2/117 (1.7%)		0/116 (0%)
Skin and subcutaneous tissue disorders
Rash	2/116 (1.7%)		2/117 (1.7%)		4/116 (3.4%)
Eczema	0/116 (0%)		0/117 (0%)		2/116 (1.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.