SYNOPSIS
Name of Sponsor/Company
Name of Finished ProductDaiichi Sankyo Co., Ltd.
Adsorbed cell culture-derived H5N1 influenza virus vaccine
30μg/mL intramuscular injection “Kitasato Daiichi Sankyo”
Adsorbed cell culture-derived H5N1 influenza virus vaccine
60μg/mL intramuscular injection “Kitasato Daiichi Sankyo”

Investigators

Inactivated influenza vaccine
A randomized, double-blind, controlled study of KIB-PCI inJapanese healthy adult volunteers－Study Centre(s)5 sitesPublication (reference)

None

Studied Period－Phase of Development

Phase 3To assess the non-inferiority of KIB-PCI to Egg-derived influenza
A (H5N1) vaccine in immunogenicity in Japanese healthy adultvolunteers
A multicenter, randomized, double-blind, parallel-group,
active-controlled study
Planned: 800 subjects
KIB-PCI group: 400 subjects, Egg-derived influenza A (H5N1)
vaccine group: 400 subjects
Enrolled: 802 subjects
KIB-PCI group: 401 subjects, Egg-derived influenza A (H5N1)
vaccine group: 401 subjects
Analyzed (Safety):800 subjects
KIB-PCI group: 400 subjects, Egg-derived influenza A (H5N1)
vaccine group: 400 subjects
Analyzed (Immunogenicity): 794 subjects
KIB-PCI group: 398 subjects, Egg-derived influenza A (H5N1)
vaccine group: 396 subjects
Diagnosis:
Healthy Japanese adult volunteers
Inclusion:
1) An age range from 20 to 64 years old at the time of obtaining
informed consents
2) A subject without any health problems to participate in thestudy, judged by investigators or sub investigators
3) Able to comply with all trial procedures, take examinations
stipulated in the protocol, and report their symptoms
Test product (batch number):
KIB-PCI 15 μg/mL formulation (CR-PCI-012)
Dosage and administration:
Two-dose intramuscular administration of KIB-PCI (0.5 mL) at
15 μg (as HA content)
Each vaccination was administered in the deltoid region on
opposite sides of the body, 14-28 days apart.
6 weeks
Controlled product (batch number):Egg-derived influenza A (H5N1) vaccine 15 μg/mL formulation(CR-PIA-102)

Name of Active Ingredient
Title of Study

Objectives
Methodology
Number of Patients (plannedand analyzed)

Diagnosis and Main Criteriafor Inclusion

Test Product, Dose and Modeof Administration, Batch
NumberDuration of TreatmentReference Therapy, Dose andModeofAdministration,

Batch Number

Criteria for Evaluation

Statistical Method

Summary - Conclusion

Dosage and administration:
Two-doses intramuscular administration of Egg-derived influenza
A (H5N1) vaccine (0.5 mL) at 15 μg (as HA content)
Each vaccination was administered in the deltoid region on
opposite sides of the body, 14-28 days apart.
Primary endpoint:
The difference in seroconversion rates (SCR) of the SRH
antibody against the H5 antigen
The ratio of geometric means titer (GMTR) of the SRH antibody
against the H5 antigen
Secondary endpoint:
SRH antibody titer against the H5 antigen
HI antibody titer against the H5 antigen
Neutralizing antibody titer against the H5N1 influenza virus
The immunologic non-inferiority of KIB-PCI to the control
vaccine (Egg-derived influenza A (H5N1) vaccine) was assessed.
The non-inferiority was demonstrated if both of the following
criteria were satisfied at approximately 3 weeks after the 2ndvaccination.
1) The upper limit of the 2-sided 95% CI for the difference in SCR(control vaccine minus KIB-PCI) did not exceed 10%.
2) The upper limit of the 2-sided 95% CI for the ratio of GMTR on
the basis of GMT before the 1st vaccination (control vaccine
divided by KIB-PCI) did not exceed 1.5.
Immunogenicity summary:
SCR of SRH antibody measured by using homologous antigen
approximately 3 weeks after the 2nd vaccination was 55.67% (95%CI: 50.57 to 60.68) in the KIB-PCI group and 95.54% (95% CI:92.95 to 97.38) in the control vaccine group. The difference inSCR was 39.87% (95% CI: 34.37 to 45.11). The GMTR of theSRH antibody approximately 3 weeks after the 2nd vaccination
calculated by using homologous antigen was 3.816 (95% CI: 3.432to 4.242) in the KIB-PCI group, and 9.850 (95% CI: 9.136 to10.621) in the control vaccine group. The GMTR ratio was 2.582(95% CI: 2.281 to 2.922). Immunologic non-inferiority of KIB-PCIto the control vaccine was not declared by evaluating the differencein SCR and the ratio of GMTR of the SRH antibody.
Additional analysis was conducted by using cell cultured antigen
after unblinding of the randomization schedule.
SCR of the SRH antibody approximately 3 weeks after the 2ndvaccination was 55.67% (95% CI: 50.57 to 60.68) in the KIB-PCIgroup and 50.92% (95% CI: 45.78 to 56.05) in the control vaccine
group. The difference in SCR was ‐4.75% (95%CI: ‐11.73 to2.29). The GMTR of the SRH antibody approximately 3 weeks
after the 2nd vaccination was 3.898 (95% CI: 3.512 to 4.326) in theKIB-PCI group, and 4.622 (95% CI: 4.189 to 5.099) in the control
vaccine group. The GMTR ratio was 1.186 (95%CI: 1.033 to1.361). Immunologic non-inferiority of KIB-PCI to the control
vaccine was shown by evaluating the difference in SCR and theratio of GMTR of the SRH antibody.
Safety summary:
The incidence of adverse events was 79.5% (318/400) in theKIB-PCI group and 88.3% (353/400) in the control vaccine group.
There were no major differences between the two groups in termsof the incidence of adverse events. 1 SAE was reported by 1

Date of Reportsubject in the KIB-PCI group (Seventh nerve palsy reported asright facial palsy) and 1 SAE reported by 1 subject in the control
vaccine group (completed suicide). Although seventh nerve palsy
was considered as a reactivation of the varicella-zoster virus by theinvestigator, it was considered vaccination-related because it
occurred approximately 8 days post-vaccination with KIB-PCI.
The subject recovered from this SAE. Completed suicide wasconsidered by the investigator that it was unlikely related to thevaccination.
Conclusion:
Immunologic non-inferiority of KIB-PCI to the control vaccine
was not declared by evaluating the difference in SCR and the ratioof GMTR of the SRH antibody.
There were no major differences in the incidence of adverse
events between the two groups. In conclusion, KIB-PCI had nosignificant safety concerns, compared with the control vaccine.
March 12, 2015