Concomitant Vaccination With the Japanese Encephalitis Vaccine IC51 and HARVIX® 1440

• Sponsor: Valneva Austria GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00596271
• Collaborator: (none)
• Enrollment: 192
• Arms: 3
• Duration (Months): 35

Study Details

Study Description

Brief Summary

The objective is to investigate the immunogenicity of the Japanese Encephalitis vaccine IC51 (JE-PIV) single and concomitant with HAVRIX® 1440

Condition or Disease	Intervention/Treatment	Phase
Japanese Encephalitis	Biological: IC51; Biological: HAVRIX; Other: Placebo	Phase 3

Detailed Description

This is a randomized, controlled, multi-center, single-blind phase 3 study. The study population consists of male and female healthy subjects, aged at least 18 years.

192 subjects will be enrolled at 2 sites in Europe.

Study Design

• Study Type: Interventional
• Actual Enrollment: 192 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity of Concomitant Vaccination With IC51 and HARVIX® 1440 in Healthy Subjects. A Single-blind Randomized, Controlled Phase 3 Study
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Jul 1, 2006
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: IC51 and Placebo 6 mcg i.m. IC51 with 2 injections (day 0 and 28)and placebo 0.5 mL with 1 injection (day 0)	Biological: IC51; Other Names: Japanese Encephalitis purified inactivated vaccine ; Other: Placebo
Active Comparator: HAVRIX and placebo HAVRIX with 1 injection (day 0) and placebo 0.5 mL with 2 injections (day 0 and 28)	Biological: HAVRIX; Other: Placebo
Active Comparator: IC51 and HAVRIX IC51 6 mcg i.m. with 2 injections (day 0 and 28) and HAVRIX with 1 injection (day 0)	Biological: IC51; Other Names: Japanese Encephalitis purified inactivated vaccine ; Biological: HAVRIX

Outcome Measures

Primary Outcome Measures

1. Geometric Mean Titer (GMT) at Day 56 for Anti-JEV Neutralizing Antibodies [Day 56]

   anti-JEV Neutralizing Antibodies were tabulated for IC51 groups only; for HAV GMTs (co-primary endpoint GMT for Hepatitis A Virus (HAV) Antibody at Day 28), please refer to "Outcome 2" within outcome measure section

2. GMT for Hepatitis A Virus (HAV) Antibody at Day 28 [Day 28]

Secondary Outcome Measures

1. Seroconversion Rate (SCR) at Day 56 for Plaque Reduction Neutralization Assay (PRNT) and HAV at Day 28 [day 28 and 56]

2. GMT and SCR for PRNT at Day 28 and HAV at Day 56 [day 28 and 56]

3. Safety [until 6 month after last vaccination]

   Rate of Adverse Events (AEs), Serious Adverse Events (SAEs) and medically attended AEs, local and systemic tolerability, changes in safety laboratory parameters (hematology, serum chemistry, urinalysis)

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

• In female subjects either childbearing potential terminated by surgery or one year post-menopausal, or a negative serum pregnancy test during screening and the willingness not to become pregnant during the study period and 30 days after the last vaccination by practicing reliable methods of contraception

• Written informed consent obtained prior to study entry

Exclusion Criteria:

• History of clinical manifestation of any flavivirus infection

• History of vaccination against Japanese encephalitis (JE), Yellow fever and Dengue fever (an anti-JEV neutralizing antibody titer >= 1:10 at baseline is acceptable for inclusion, these subjects will be part of the safety population, but will not be analyzed for immunogenicity in the per-protocol analysis)

• History of any previous Hepatitis A vaccination and infection

• Use of any other investigational or non-registered drug or vaccine in addition to the study vaccine during the study period or within 30 days preceding the first dose of study vaccine

• Planned administration of another vaccine during the study period

• Immunodeficiency including post-organ-transplantation or immunosuppressive therapy

• A family history of congenital or hereditary immunodeficiency

• History of autoimmune disease

• Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of vaccination.

• Any acute infections within 4 weeks prior to enrollment

• Infection with human immunodeficiency virus (HIV), Hepatitis B (HBsAg) or Hepatitis C

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Valneva Austria GmbH

Investigators

• Study Director: Astrid Kaltenboeck, Ph.D., Valneva Austria GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Valneva Austria GmbH
• ClinicalTrials.gov Identifier: NCT00596271
• Other Study ID Numbers: IC51-308
• First Posted: Jan 16, 2008
• Last Update Posted: May 13, 2014
• Last Verified: Apr 1, 2014

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

Study Results

Participant Flow

Recruitment Details	First Subject In: 26.09.2005, Last Subject Out: 14.07.2006 performed at centers for travelling medicine/vaccinology

Arm/Group Title	IC51 and Placebo	HAVRIX and Placebo	IC51 and HAVRIX
Arm/Group Description	6 mcg i.m. IC51 with 2 injections (day 0 and 28)and placebo 0.5 mL with 1 injection (day 0)	HAVRIX with 1 injection (day 0) and placebo 0.5 mL with 2 injections (day 0 and 28)	IC51 6 mcg i.m. with 2 injections (day 0 and 28) and HAVRIX with 1 injection (day 0)
Period Title: Overall Study
STARTED	65	65	62
COMPLETED	60	59	61
NOT COMPLETED	5	6	1

Baseline Characteristics

Arm/Group Title	IC51 and Placebo	HAVRIX and Placebo	IC51 and HAVRIX	Total
Arm/Group Description	6 mcg i.m. IC51 with 2 injections (day 0 and 28)and placebo 0.5 mL with 1 injection (day 0)	HAVRIX with 1 injection (day 0) and placebo 0.5 mL with 2 injections (day 0 and 28)	IC51 6 mcg i.m. with 2 injections (day 0 and 28) and HAVRIX with 1 injection (day 0)	Total of all reporting groups
Overall Participants	65	65	62	192
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	65 100%	65 100%	62 100%	192 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	34 52.3%	35 53.8%	34 54.8%	103 53.6%
Male	31 47.7%	30 46.2%	28 45.2%	89 46.4%
Region of Enrollment (participants) [Number]
Europe	65 100%	65 100%	62 100%	192 100%

Outcome Measures

1. Primary Outcome

Title	Geometric Mean Titer (GMT) at Day 56 for Anti-JEV Neutralizing Antibodies
Description	anti-JEV Neutralizing Antibodies were tabulated for IC51 groups only; for HAV GMTs (co-primary endpoint GMT for Hepatitis A Virus (HAV) Antibody at Day 28), please refer to "Outcome 2" within outcome measure section
Time Frame	Day 56

Outcome Measure Data

Analysis Population Description

Per Protocol Population includes all randomized subjects without major protocol deviations

Arm/Group Title	IC51 and Placebo	IC51 and HAVRIX
Arm/Group Description
Measure Participants	58	58
Geometric Mean (95% Confidence Interval) [titers]	192.2	202.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IC51 and Placebo, IC51 and HAVRIX
	Comments	The primary efficacy analysis will compare the IC51+HAVRIX vs. IC51+Placebo group in terms of the GMT for anti- JEV neutralizing antibody at day 56. An observed cases approach will be applied for the primary analysis
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority of the combined administration is postulated, if the lower bounds of both twosided 95% confidence intervals for the GMT ratios (of combined vaccination over single vaccination) are > 1/2. This procedure is equivalent to the approach based on a 1-sided test with a significance level of 2.5% for each comparison with the null hypothesis H0 : ratio ≤ 0.5 versus the alternative hypotheses H1 : ratio > 0.5.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	Seroconversion Rate (SCR) at Day 56 for Plaque Reduction Neutralization Assay (PRNT) and HAV at Day 28
Time Frame	day 28 and 56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	GMT and SCR for PRNT at Day 28 and HAV at Day 56
Time Frame	day 28 and 56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Safety
Description	Rate of Adverse Events (AEs), Serious Adverse Events (SAEs) and medically attended AEs, local and systemic tolerability, changes in safety laboratory parameters (hematology, serum chemistry, urinalysis)
Time Frame	until 6 month after last vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Primary Outcome

Title	GMT for Hepatitis A Virus (HAV) Antibody at Day 28
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HAVRIX + Placebo	IC51 + HAVRIX
Arm/Group Description
Measure Participants	52	58
Geometric Mean (95% Confidence Interval) [titers]	21.7	24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IC51 and Placebo, IC51 and HAVRIX
	Comments	The primary efficacy analysis will compare the IC51+HAVRIX vs. HAVRIX+Placebo group in terms of the GMT for HAV antibody at day 28. An observed cases approach will be applied for the primary analysis.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority of the combined administration is postulated, if the lower bounds of both twosided 95% confidence intervals for the GMT ratios (of combined vaccination over single vaccination) are > 1/2. This procedure is equivalent to the approach based on a 1-sided test with a significance level of 2.5% for each comparison with the null hypothesis H0 : ratio ≤ 0.5 versus the alternative hypotheses H1 : ratio > 0.5.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Adverse Events

Arm/Group Title	IC51 and Placebo		HAVRIX and Placebo		IC51 and HAVRIX
Arm/Group Description	6 mcg i.m. IC51 with 2 injections (day 0 and 28)and placebo 0.5 mL with 1 injection (day 0)		HAVRIX with 1 injection (day 0) and placebo 0.5 mL with 2 injections (day 0 and 28)		IC51 6 mcg i.m. with 2 injections (day 0 and 28) and HAVRIX with 1 injection (day 0)
All Cause Mortality
	IC51 and Placebo		HAVRIX and Placebo		IC51 and HAVRIX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	IC51 and Placebo		HAVRIX and Placebo		IC51 and HAVRIX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/65 (1.5%)		0/65 (0%)		0/62 (0%)
Nervous system disorders
Convulsion	1/65 (1.5%)	1	0/65 (0%)	0	0/62 (0%)	0
Other (Not Including Serious) Adverse Events
	IC51 and Placebo		HAVRIX and Placebo		IC51 and HAVRIX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/65 (41.5%)		31/65 (47.7%)		24/62 (38.7%)
Ear and labyrinth disorders
Vertigo	1/65 (1.5%)		1/65 (1.5%)		2/62 (3.2%)
Gastrointestinal disorders
Diarrhea	1/65 (1.5%)		1/65 (1.5%)		4/62 (6.5%)
Nausea	2/65 (3.1%)		2/65 (3.1%)		2/62 (3.2%)
General disorders
Fatique	2/65 (3.1%)		5/65 (7.7%)		5/62 (8.1%)
Influenza like illness	6/65 (9.2%)		3/65 (4.6%)		3/62 (4.8%)
Pyrexia	2/65 (3.1%)		0/65 (0%)		2/62 (3.2%)
Infections and infestations
Nasopharyngitis	4/65 (6.2%)		4/65 (6.2%)		5/62 (8.1%)
Cystitis	1/65 (1.5%)		1/65 (1.5%)		2/62 (3.2%)
Rhinitis	2/65 (3.1%)		0/65 (0%)		2/62 (3.2%)
Bronchitis	1/65 (1.5%)		0/65 (0%)		2/62 (3.2%)
Gastrointeritis	0/65 (0%)		1/65 (1.5%)		2/62 (3.2%)
Rash pustular	0/65 (0%)		2/65 (3.1%)		0/62 (0%)
Investigations
Hepatic enzyme increased	2/65 (3.1%)		1/65 (1.5%)		0/62 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	0/65 (0%)		1/65 (1.5%)		2/62 (3.2%)
Nervous system disorders
Headache	4/65 (6.2%)		10/65 (15.4%)		4/62 (6.5%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	3/65 (4.6%)		2/65 (3.1%)		0/62 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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