SYNOPSIS
Name of Sponsor/CompanyDaiichi Sankyo Co., Ltd., Sanofi KK

Name of Finished ProductSquarekids Subcutaneous Injection Syringe

Name of Active Ingredient

Purified diphtheria toxoid, Purified tetanus toxoid, Purified
Bordetella pertussis antigens, and inactivated polioviruses type 1, 2and 3.

Title of Study

Immunogenicity and Safety of DD-687 given subcutaneously as athree-dose primary and booster vaccination versus commerciallyavailable DTaP and OPV in infants in Japan

Investigators
Study Centre(s)23 sites

Publication (reference)

The immunogenicity and Safety of a New Quadruple Combination
Vaccine, Including Undiluted IPV (Salk vaccine)
J Jpn Pediatr Soc. 2015;119(4):669~79

Studied Period
Phase of Development

Phase 3Objectives

To demonstrate that the seroprotection rates against polio viruses
types 1, 2 and 3 are over 90% approximately 1 months following
the primary vaccination series with DD-687

Methodology

Multi-center, two-arm, randomized, unbalanced, double-blind,clinical study

Number of Patients (plannedPlanned: 374 subjects (test product 249 subjects, controlledand analyzed)

product 125 subjects)
Analyzed:Immunogenicity:
355 subjects for primary (test product 235, controlled product120)
363 subjects for booster (test product 241, controlled product122 subjects)
Safety: 376 subjects (test product 248 subjects, controlled product
128 subjects)

Diagnosis and Main Criteria

Healthy Japanese infants who fulfill all of the following criteria:

for Inclusion

1) Aged 3 months to 8 months inclusive on the day of inclusion
2) Informed consent form signed by the parent(s) or other legal
representative3) Able to attend all scheduled visits and to comply with all trial
procedures

Test Product, Dose and Modeof Administration, BatchNumber

Test product (Batch number)
DD-687 (CR-NTV-003)
Dosage and administration
For subjects allocated into group A, 0.5 mL of DD-687 as athree-dose primary vaccination every 3-8 weeks, starting at 3-68
months of age, and followed by DD-687 booster dose 6-18 months
after the three-dose primary vaccination

Duration of Treatment

Approximately 2 years

Reference Therapy, Dose andControl product (Batch number)

ModeofAdministration,

Batch Number

DTaP (AM010A)
OPV (COPV Lot1)
OPV placebo (GOPV Lot1)
Dosage and administration：
For subjects allocated into group B, 0.5 mL of DTaP as athree-dose primary vaccination every 3-8 weeks, starting at 3-68
months of age, and followed by DTaP booster dose 6-18 months
after the three-dose primary vaccination
Between completion of three-dose primary vaccination andbooster vaccination, 0.05 mL of OPV for group A or 0.05 mL ofOPV placebo for group B was orally administered two times
every 6-10 weeks.

Criteria for Evaluation

Seroprotection rate, seroconversion rate and GMT for anti-D,
anti-T, anti-PT, anti-FHA, anti-polio 1, 2 and 3 antibodies after
three-dose primary vaccination and booster vaccination

Statistical Method

Seroprotection and seroconversion rate with their 95% confidence
intervals (CIs) for each antigen were calculated at post-injection3
and post-injection4.
GMT with their 95% CIs for each antigen were calculated at
pre-injection1, post-injection3, pre-injection4 and post-injection4.
A 95% CI was constructed around the study-derived point estimateof the seroprotection rate against poliovirus 1, 2 and 3
approximately 1 month after the third dose of DD-687.

Theprimary objective was achieved if the lower bound of each of the95% CI was >90%.
For each antigen, the non-inferiority of DD-687 versus DTaP andOPV was demonstrated if the 95% CI of the difference (testvaccine minus control vaccine) lay entirely above the clinicallyacceptable limit for non-inferiority (-10%)
Reverse cumulative distribution curves were also presented.
Summary - Conclusion

Approximately 1 month after the three-dose primary vaccination
with DD-687, all infants were seroprotected against polio virus
types 1, 2 and 3.
Also, after primary series, the non-inferiority of DD-687 versus
DTaP and OPV was demonstrated for all antigens.
Additionally, DD-687 was highly immunogenic for each antigen
when administered as booster dose approximately 1 year after
completion of primary series.
DD-687 was well tolerated with similar safety profiles to DTaP+OPV.

Date of Report

24/June/2015