General Information

Ixiaro is a vaccine containing the inactivated virus strain SA14-14-2 adjuvanted with aluminum hydroxide. It is is prepared using tissue culture rather than live organisms and does not contain any stabilizers such as gelatin or preservatives in its formulation.

Ixiaro is specifically indicated for the prevention of disease caused by Japanese encephalitis virus in persons 17 years of age and older.

Ixiaro is supplied as a sterile 0.5 mL suspension in a pre-filled syringe designed for intramuscular administration. Immunization with Ixiaro consists of two doses administered 28 days apart. Immunization series should be completed at least one week prior to potential exposure to JEV. Ixiaro should be administered intramuscularly into the deltoid muscle. An accelerated dosing schedule was subsequently approved to allow for adult travelers (18-65 years old) to get 2 doses of Ixiaro 7 days apart.

Clinical Trial Results

FDA approval of Ixiaro was based on three studies.

Non-inferiority of Ixiaro Compared to U.S.-Licensed JE-VAX
The immunogenicity of Ixiaro was evaluated in a randomized, active-controlled, observer-blinded clinical trial. This study enrolled 867 healthy male and female subjects 18 to 80 years of age, in the US, Germany and Austria. Subjects in the Ixiaro treatment arm received the following schedule of three intramuscular doses: Day 0, 0.5 mL of Ixiaro, 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. Subjects in the comparator arm received a subcutaneous dose of 1.0 mL of 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. Ixiaro met predefined statistical criteria for non-inferiority compared to JE-VAX. The seroconversion rate at Day 56 was 96.4% in the Ixiaro arm and 93.8% in the JE-VAX arm. At Day 56 the GMT's were 361 for the Ixiaro arm and 364 for the JE-VAX arm.

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 trials. In the Intent-to-Treat population of subjects randomized to vaccination with Ixiaro (N=181), seroconversion rates at 6 and 12 months after initiation of the two-dose series were 95% and 83.4%, respectively. Geometric mean titers (GMT) at 6 and 12 months after initiation of the two-dose series were 83.5 and 41.2, respectively.

Temporal Evaluation of Immunogenicity of IXIARO During Vaccination Series
A randomized, observer-blinded clinical trial enrolled 374 healthy male and female subjects, aged 18-76 years, to evaluate the immunogenicity of Ixiaro on days 10, 28, 35, and 56 during the vaccination period. On Days 10 and 28, following dose #1, the seroconversion rates were 21.1% and 39.8%, respectively. On Days 35 and 56, following dose #2, the seroconversion rates were 97.3% for both days.