Recommended Topic Related To:

Ixiaro

"Thanks to effective vaccine, the United States has been polio-free since 1979. But poliovirus is still a threat in some countries. Be part of the success story and get your child vaccinated on schedule.

Polio, or poliomyelitis, is an in"...

Ixiaro

CLINICAL PHARMACOLOGY

Mechanism of Action

Japanese encephalitis is a disease caused by the mosquito-borne Japanese encephalitis virus (JEV). IXIARO (japanese encephalitis vaccine) acts by inducing antibodies that neutralize live JEV.

Clinical Studies

Clinical efficacy trials of JE vaccines have found that neutralizing antibody, as measured by a Plaque Reduction Neutralization Test (PRNT) is protective against JEV infection6. Therefore, the evaluation of the efficacy of IXIARO (japanese encephalitis vaccine) was based on immunogenicity using PRNT as a serological correlate of protection. The World Health Organization consultation group recognizes a PRNT titer of ≥ 1:10 as being a reasonable correlate for protection7.

Clinical Trial2 of Immunogenicity of IXIARO (japanese encephalitis vaccine) – Non-inferiority of IXIARO (japanese encephalitis vaccine) Compared to U.S.-Licensed JE Vaccine, JE-VAX

Immunogenicity of the vaccine was evaluated in a randomized, active-controlled, observer-blinded clinical trial conducted in the U.S., Germany and Austria in 867 healthy male and female subjects 18 to 80 years of age (mean age: 41.3 years; 60.8% female; race: White 80.8%, Asian 0.8%, Black 13.1%, Other 5.3%). Subjects in the IXIARO (japanese encephalitis vaccine) treatment arm received the following schedule of three intramuscular doses: Day 0, 0.5 mL of IXIARO (japanese encephalitis vaccine) , Day 7, PBS + Al(OH)3 (0.5 mL phosphate buffered saline with 0.1% aluminum hydroxide), and on Day 28, 0.5 mL of IXIARO (japanese encephalitis vaccine) . Subjects in the comparator arm received a subcutaneous dose of 1.0 mL of the US-licensed JEV vaccine, JE-VAX, on Days 0, 7 and 28.

The co-primary endpoints were seroconversion rate (SCR), defined as anti-JEV antibody titer ≥ 1:10, and geometric mean titer (GMT) at Day 56 in the per protocol population. The immune responses elicited by IXIARO (japanese encephalitis vaccine) met predefined statistical criteria for non-inferiority compared to those induced by JE-VAX. See Table 3.

Table 3: Seroconversion Rates and Geometric Mean Titers After IXIARO (japanese encephalitis vaccine) or JE-VAX, Per Protocol Population

Seroconversion Rates
Time Point IXIARO (japanese encephalitis vaccine)
SCR (n/N)
[95% CI]
JE-VAX
SCR (n/N)
[95% CI]
Rate difference
[95% CI]
Pre-Vaccination Screen 0 0  
Day 56 (28 days after vaccine dose #2) 96.4% (352/365)
[94.0, 97.9]
93.8% (347/370)
[90.9, 95.8]
2.6%
[-0.5,6.0]†
Geometric Mean Titers
Time Point IXIARO (japanese encephalitis vaccine)
N=365
n (GMT)
[95% CI's]
JE-VAX
N=370n (GMT) [95% CI's]
GMT ratio estimator
[95% CI]
Pre-Vaccination Screen 365 (5.0) 370 (5.0)  
Day 56 (28 days after vaccine dose #2) 361 (243.6)
[ 216.4, 274.1]
364 (102.0)
[90.3, 115.2 ]
2.33
[1.97, 2.75]‡
†Seroconversion Rates (SCRs): Non-inferiority of IXIARO (japanese encephalitis vaccine) compared to JE-VAX for SCRs was demonstrated if the lower bound of the 2-sided 95% confidence interval (CI) for the SCR difference (IXIARO (japanese encephalitis vaccine) minus JE-VAX) was > -10% at Day 56.
‡Geometric Mean Titers (GMTs): Non-inferiority of IXIARO (japanese encephalitis vaccine) compared to JE-VAX for GMTs was demonstrated if the lower bound of the 2-sided 95% CI for the GMT ratio (IXIARO (japanese encephalitis vaccine) /JE-VAX) was > 1/1.5 at Day 56.
◊Pre-Vaccination titers were negative by definition in the PP population and have been imputed to 5.

Follow-up Study of Long Term Immunogenicity (6 months and 12 months)

The persistence of JE-neutralizing antibody was evaluated in a subgroup of subjects recruited for follow-up after participation in one of two clinical trials1, 2. In the Intent-to-Treat (ITT) population of subjects randomized to vaccination with IXIARO (japanese encephalitis vaccine) (N=181), seroconversion rates (SCR) at 6 and 12 months after initiation of the two-dose series were 95% [95%CI 90.8,97.4] and 83.4% [95%CI 77.3,88.1], respectively. Geometric mean titers (GMT) at 6 and 12 months after initiation of the two-dose series were 83.5 [95%CI 70.9,98.4] and 41.2 [95%CI 34.4,49.3], respectively.

Temporal Evaluation of Immunogenicity of IXIARO (japanese encephalitis vaccine) During Vaccination Series

In a randomized, dosing regimen, observer-blinded clinical trial4 in 374 healthy male and female subjects, aged 18-76 years, the immunogenicity of IXIARO (japanese encephalitis vaccine) was evaluated on days 10, 28, 35, and 56 during the vaccination period. Seroconversion rates (SCR) at each time point for the subjects randomized to the standard dosing regimen (IXIARO (japanese encephalitis vaccine) on days 0 and 28) are displayed in Table 4.

Table 4: Seroconversion Rates (SCR) During the Vaccination Series (IXIARO (japanese encephalitis vaccine) on Days 0 and 28), Per Protocol Population

Day 0 (Dose #1 administered) Day 10
(10 days post dose #1)
SCR (n/N)
[95% CI]
Day 28
(28 days post dose #1)
SCR (n/N)
[95% CI]
Day 28 (Dose #2 administered) Day 35
(7 days post dose #2)
SCR (n/N)
[95% CI]
Day 56
(28 days post dose #2)
SCR (n/N)
[95% CI]
21.1% (24/114) 39.8% (45/113) 97.3% (110/113) 97.3% (110/113)
[13.6%; 28.5%] [30.8%; 48.8%] [94.4%; 100.0%] [94.4%, 100%]

Clinical Trial3 of Immunogenicity of IXIARO (japanese encephalitis vaccine) and the Hepatitis A Vaccine, HAVRIX, When Used Concomitantly

The concomitant use of IXIARO (japanese encephalitis vaccine) with inactivated Hepatitis A Virus vaccine (HAVRIX) was evaluated in a randomized, controlled, single-blind clinical trial including 192 healthy male and female subjects aged 18 to 61 years. Subjects were divided into three treatment groups: Group A (N=62) received IXIARO (japanese encephalitis vaccine) + HAVRIX; Group B (N=65) received IXIARO (japanese encephalitis vaccine) + control [PBS + Al(OH)3] (0.5mL phosphate buffered saline with 0.1% aluminum hydroxide by intramuscular injection); Group C (N=65) received HAVRIX + control [PBS + Al(OH)3]. Anti-JEV GMT at Day 56 in Group A met non-inferiority criteria compared to anti-JEV GMT at Day 56 in Group B. In addition, anti-HAV GMT at Day 28 in Group A met non-inferiority criteria compared to anti-HAV GMT at Day 28 in Group C. Therefore, concomitant administration of IXIARO (japanese encephalitis vaccine) and HAVRIX did not adversely affect immunogenicity compared to administration of either vaccine individually. Safety results regarding co-administration of IXIARO (japanese encephalitis vaccine) with HAVRIX are summarized in Section 6.2, Clinical Trials Experience.

REFERENCES

1. Clinical study referred to as NCT00605085 in the National Library of Medicine clinical trial database, also referred to as study IC51-302 in the Biologics License Application.

2. Clinical study referred to as NCT00604708 in the National Library of Medicine clinical trial database, also referred to as study IC51-301 in the Biologics License Application.

4. Clinical study referred to as NCT00595790 in the National Library of Medicine clinical trial database, also referred to as study IC51-304 in the Biologics License Application.

6. Hoke CH, Nisalak A, Sangawhipa N, Jatanasen S, Laorakapongse T, Innis BL, Kotchasenee S, Gingrich JB, Latendresse J, Fukai K, et al. Protection against Japanese encephalitis by inactivated vaccines. N Engl J Med. 1988 Sep 8;319(10):608-14.

7. Hombach J, Solomon T, Kurane I, Jacobson J, Wood D. Report on a WHO consultation on immunological endpoints for evaluation of new Japanese encephalitis vaccines, WHO, Geneva, 2-3 September, 2004. Vaccine. 2005;23:5205-11.

Last reviewed on RxList: 3/11/2010
This monograph has been modified to include the generic and brand name in many instances.

A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Women's Health

Find out what women really need.