Open-label, Randomized Study in a Pediatric Population in a JEV (Japanese Encephalitis Virus)-Endemic Country

• Sponsor: Valneva Austria GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01296360
• Collaborator: (none)
• Enrollment: 300
• Locations: 3
• Arms: 2
• Duration (Months): 34
• Patients Per Site: 100
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

This is a randomized, open-label Phase 3 study including children aged >9 months to <17 years and 7 months who have been vaccinated with IXIARO in study IC51-323.

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

Detailed Description

This is a randomized, open-label Phase 3 study including children aged >9 months to <17 years and 7 months who have been vaccinated with IXIARO in the previous study IC51-323.

Study Design

• Study Type: Interventional
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Long-Term Immunity and Safety With or Without a Booster Dose Following Primary Vaccination With the Japanese Encephalitis Vaccine IC51 (IXIARO®) in a Pediatric Population in a JEV-Endemic Country. Open-Label, Randomized, Phase 3 Study
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: >14 months to <2 years IXIARO 0.25 ml i.m. (milliliter, intramuscular)	Biological: IXIARO; 0.25 ml i.m. (milliliter, intramuscular)
Active Comparator: >3 years - <18 years IXIARO 0.5 ml i.m (milliliter, intramuscular)	Biological: IXIARO; 0.5 ml i.m. (milliliter, intramuscular)

Outcome Measures

Primary Outcome Measures

1. SCRs (Seroconversion Rate) as Defined by Percentage of Subjects With Plaque Reduction Neutralization Test Titers of>1:10 at 1 Month After the Booster Dose [1 month post booster]

Secondary Outcome Measures

1. Rate of Subjects Achieving a >4-fold Increase in JEV (Japanese Encephalitis Virus) Neutralizing Antibody Titers at 1 Month After the Booster Dose [1 month]

2. GMTs (Geometric Mean Titre) for JEV Neutralizing Antibodies Measured Using a Validated PRNT (Plaque Reduction Neutralization Test) at 1 Month After the Booster Dose [1 month]

3. GMTs and Rate of Subjects With a PRNT Titer of >1:10 at Months 12, 24 and 36 After First IXIARO Vaccination in IC51-323 With and Without Booster Vaccination [36 months]

4. Rate of Subjects With SAEs (Serious Adverse Events) Following Immunization and Medically Attended AEs (Adverse Events) up to Months 12, 24 and 36 After the First IXIARO Vaccination in IC51 323 With and Without Booster Vaccination. Severity, Duration and [36 months]

5. Rate of Subjects With Unsolicited AEs (Adverse Events) up to Months 12, 24 and 36 After the First IXIARO Vaccination in IC51 323 With and Without Booster Vaccination. Severity, Duration and Relationship to Vaccinations. [36 months]

6. Rate of Subjects With SAEs and Medically Attended AEs Within 1 Month Following the Booster Dose. Severity, Duration and Relationship to Vaccinations. [1 month]

7. Rate of Subjects With Unsolicited AEs Within 1 Month Following the Booster Dose. Severity, Duration and Relationship to Vaccinations. [1 month]

8. Rate of Subjects With Solicited AEs for up to 7 Days Following the Booster Dose. Severity and Duration. [7 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Months to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Children and adolescents who have completed study IC51-323 and received both IXIARO vaccinations according to protocol.

• Children who have received the dose confirmed for their age group.

• Male or female healthy children and adolescents aged ≥9 months to <17 years and 7 months at the time of enrolment into this study.

• Written informed consent by the subject's legal representative(s), according to local requirements, and written informed assent of the subject, if applicable.

• Female subjects: either no childbearing potential or negative pregnancy test (pregnancy test to be performed in female subjects after onset of menarche) at Visits 1, 2 and 2a as stipulated by the protocol. For females after menarche willingness to practice a reliable method of contraception

Exclusion Criteria:

• Vaccination against JE virus (JEV) (except within study IC51-323 and IC51 325), Yellow fever, West Nile virus and Dengue fever at any time prior to or planned during the study.

• History of or clinical manifestation of any Flavivirus disease during IC51-323 or IC51

• Participation in another study with an investigational drug during IC51 323 or IC51

• Planned active or passive immunization within 2 weeks before and 1 week after the IXIARO booster.

• History of or development of any immunodeficiency including post-organ-transplantation after inclusion into IC51-323 or IC51 325.

• History of or development of an autoimmune disease during study IC51-323 or IC51 325.

• Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying medications started during IC51-323 or IC51 325. (For corticosteroids, this would mean prednisone or equivalent at >0.05 mg/kg/day; topical and inhaled steroids are allowed).

• Acute febrile infection at Visit 2 (only for the Booster Group).

• Pregnancy (positive pregnancy test at Visit 1 and Visit 2), lactation or unreliable contraception in female subjects after onset of menarche.

• Hypersensitivity reactions to IXIARO or adverse events in study IC51-323 requiring withdrawal from further vaccination or anaphylaxis or severe cases of atopy requiring emergency treatment or hospital admission during IC51-323 or IC51 325.

• History of urticaria after hymenoptera envenomation, drugs, physical or other provocations or of idiopathic cause during IC51-323 or IC51 325.

• Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) (measurement of Hepatitis B surface antigen [HBsAg] titers) or hepatitis C virus (HCV).

• Illicit drug use and/or current drug or alcohol addiction.

• Inability or unwillingness by the legal representative(s) and/or the subject (where applicable) to provide informed consent/assent and to abide by the requirements of the study.

• Persons who have been committed to an institution (by a court or by an authority).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Institute for Tropical Medicine - Clinical Research Division	Muntinlupa City	Alabang	Philippines	1781
2	Research Institute for Tropical Medicine	Muntinlupa City	Alabang	Philippines	1781
3	UP-Philippine General Hospital	Manila		Philippines	1000

Sponsors and Collaborators

• Valneva Austria GmbH

Investigators

• Study Chair: Vera Kadlecek, Mag., Valneva Austria GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Valneva Austria GmbH
• ClinicalTrials.gov Identifier: NCT01296360
• Other Study ID Numbers: IC51-325
• First Posted: Feb 15, 2011
• Last Update Posted: Dec 19, 2014
• Last Verified: Dec 1, 2014

• Keywords provided by Valneva Austria GmbH: immune response; IC51-325; Japanese Encephalitis; Intercell AG
• Additional relevant MeSH terms: Encephalitis, Japanese; Encephalitis

Study Results

Participant Flow

Arm/Group Title	Booster Group	Non-Booster Group
Arm/Group Description	IC51 booster vaccination ~12 months after primary immunization in study IC51-323	No treatment in study IC51-325
Period Title: Overall Study
STARTED	150	150
Visit 2 (Month 12)	148	149
Visit 2a (Month 13)	148	0
COMPLETED	144	142
NOT COMPLETED	6	8

Baseline Characteristics

Arm/Group Title	Booster Group	Non-Booster Group	Total
Arm/Group Description	IC51 booster vaccination ~12 months after primary immunization in study IC51-323	No treatment in study IC51-325	Total of all reporting groups
Overall Participants	150	150	300
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.23 (5.084)	5.36 (5.135)	5.30 (5.101)
Sex: Female, Male (Count of Participants)
Female	72 48%	79 52.7%	151 50.3%
Male	78 52%	71 47.3%	149 49.7%

Outcome Measures

1. Primary Outcome

Title	SCRs (Seroconversion Rate) as Defined by Percentage of Subjects With Plaque Reduction Neutralization Test Titers of>1:10 at 1 Month After the Booster Dose
Time Frame	1 month post booster

Outcome Measure Data

Analysis Population Description

Intent-to-treat Population: primary analysis population for the immunogenicity analyses; defined as all subjects randomized

Arm/Group Title	>14 Months to <2 Years	>3 Years - <18 Years
Arm/Group Description	booster vaccination: IXIARO 0.25 ml i.m. (milliliter, intramuscular)	booster vaccination: IXIARO 0.5 ml i.m (milliliter, intramuscular)
Measure Participants	81	67
Number (95% Confidence Interval) [percentage of subjects]	100	100

2. Secondary Outcome

Title	Rate of Subjects Achieving a >4-fold Increase in JEV (Japanese Encephalitis Virus) Neutralizing Antibody Titers at 1 Month After the Booster Dose
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	GMTs (Geometric Mean Titre) for JEV Neutralizing Antibodies Measured Using a Validated PRNT (Plaque Reduction Neutralization Test) at 1 Month After the Booster Dose
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	GMTs and Rate of Subjects With a PRNT Titer of >1:10 at Months 12, 24 and 36 After First IXIARO Vaccination in IC51-323 With and Without Booster Vaccination
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Rate of Subjects With SAEs (Serious Adverse Events) Following Immunization and Medically Attended AEs (Adverse Events) up to Months 12, 24 and 36 After the First IXIARO Vaccination in IC51 323 With and Without Booster Vaccination. Severity, Duration and
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Rate of Subjects With Unsolicited AEs (Adverse Events) up to Months 12, 24 and 36 After the First IXIARO Vaccination in IC51 323 With and Without Booster Vaccination. Severity, Duration and Relationship to Vaccinations.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Rate of Subjects With SAEs and Medically Attended AEs Within 1 Month Following the Booster Dose. Severity, Duration and Relationship to Vaccinations.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Rate of Subjects With Unsolicited AEs Within 1 Month Following the Booster Dose. Severity, Duration and Relationship to Vaccinations.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Rate of Subjects With Solicited AEs for up to 7 Days Following the Booster Dose. Severity and Duration.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Booster Group		Non-Booster Group
Arm/Group Description	IC51 booster vaccination ~12 months after primary immunization in study IC51-323		No treatment in study IC51-325
All Cause Mortality
	Booster Group		Non-Booster Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Booster Group		Non-Booster Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/150 (4.7%)		3/150 (2%)
Infections and infestations
Abscess	1/150 (0.7%)		0/150 (0%)
Amoebic dysentery	1/150 (0.7%)		0/150 (0%)
Bronchopneumonia	1/150 (0.7%)		0/150 (0%)
Dengue fever	1/150 (0.7%)		0/150 (0%)
Gastroenteritis	1/150 (0.7%)		0/150 (0%)
Urinary tract infection	1/150 (0.7%)		0/150 (0%)
Injury, poisoning and procedural complications
Concussion	0/150 (0%)		1/150 (0.7%)
Injury	0/150 (0%)		1/150 (0.7%)
Pneumothorax traumatic	0/150 (0%)		1/150 (0.7%)
Nervous system disorders
Paralysis	0/150 (0%)		1/150 (0.7%)
Surgical and medical procedures
Finger amputation	1/150 (0.7%)		0/150 (0%)
Other (Not Including Serious) Adverse Events
	Booster Group		Non-Booster Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/150 (66%)		100/150 (66.7%)
General disorders
Pyrexia	10/150 (6.7%)		8/150 (5.3%)
Fever	12/150 (8%)		0/150 (0%)
Infections and infestations
Upper respiratory tract infection	37/150 (24.7%)		34/150 (22.7%)
Rhinitis	17/150 (11.3%)		16/150 (10.7%)
Nasopharyngitis	16/150 (10.7%)		15/150 (10%)
Varicella	9/150 (6%)		14/150 (9.3%)
Gastroenteritis	7/150 (4.7%)		8/150 (5.3%)
Bronchitis	6/150 (4%)		8/150 (5.3%)
Impetigo	10/150 (6.7%)		4/150 (2.7%)
Viral infection	9/150 (6%)		5/150 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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