臨床研究等提出・公開システム

A multicenter, open-label, uncontrolled study to confirm the safety and immunogenicity of single intramuscular dose of KD2-396 in infants who have completed three doses of DPT-IPV, freeze-dried Haemophilus b vaccine (hereafter Hib vaccine) and hepatitis B vaccine

KD2-396 I

30

The median age (range) at the time of the investigational product vaccination was 12.5 (11-16) months. The number of subjects (percentage) by age group was 6 (20.0%) less than 12 months, 17 (56.7%) at 12 to 13 months, 6 (20.0%) at 14 to 15 months, 1 (3.3%) at 16 to 17 months, and 0 (0%) at 18 months or more. The number (percentage) of male subjects was 16 (53.3%).

In this study, the planned number of subjects was 30. Of the 30 subjects who gave informed consent, all 30 were vaccinated with the investigational product and completed blood sampling after vaccination. None of the subjects dropped out of the study prior to the investigational product vaccination or discontinued the study after the investigational product vaccination.

After 27 days from the investigational product vaccination, there were no deaths due to adverse events and no serious adverse events other than deaths, significant adverse events, or severe (Grade 3) adverse events occurred. After the investigational product vaccination, the incidence of all adverse events (the number of subjects and events) was 86.7% (26 subjects and 70 events). The incidence (the number of subjects and events) of specified local adverse events (specific local adverse reaction) up to 6 days after vaccination was 36.7% (11 subjects and 19 events). The incidence of specified systemic adverse events (the number of subjects and events) up to 6 days after vaccination was 16.7% (5 subjects and 5 events). The incidence of non-specified adverse events (the number of subjects and events) up to 27 days after vaccination was 76.7% (23 subjects and 46 events). The incidence of all adverse reactions (the number of subjects and events) was 40.0% (12 subjects and 27 events).

Primary outcome analysis -Before and after the investigational product vaccination, GMFR (95% confidence interval) for PT, FHA, diphtheria toxin, tetanus toxoid, PRP, and HBsAg were 4.62 (3.69-5.78), 5.60 (4.50-6.98), 6.17 (4.46-8.55), 7.93 (5.33-11.81), 51.99 (31.06-87.03), and 1.36 (1.12-1.64). -Before and after the investigational product vaccination, the mean (95% confidence interval) of differences in antibody titers (log2) against attenuated poliovirus types 1, 2, 3 were 3.89 (3.36-4.42), 4.68 (4.25-5.11), and 4.70 (4.12-5.27). Secondary outcome analysis -After the investigational product vaccination, the prevalence of antibodies above the protective threshold (95% confidence interval) against PT, FHA, diphtheria toxin, tetanus toxoid, attenuated poliovirus types 1, 2, 3, PRP (baseline for long-term protection) and HBsAg were 100.0% (90.5%-100.0%), 100.0% (90.5%-100.0%), 100.0% (90.5%-100.0%), 100.0% (90.5%-100.0%), 100.0% (90.2%-100.0%), 100.0% (90.2%-100.0%), 100.0% (90.2%-100.0%), 100.0% (90.5%-100.0%), and 100.0% (90.5%-100.0%). -After the investigational product vaccination, GMT (95% confidence interval) for PT, FHA, diphtheria toxin, tetanus toxoid, PRP, and HBsAg were 137.4 (109.2-173.0), 148.4 (114.8-191.7), 4.78 (3.77-6.06), 0.74619 (0.54513-1.02139), 50.46 (37.51-67.89), and 920.32 (831.87-1018.17). -After the investigational product vaccination, the mean antibody titers (log2) (95% confidence interval) against attenuated poliovirus types 1, 2, 3 were 12.72 (12.02-13.43), 14.38 (14.00-14.76), and 13.10 (12.66-13.55).

Infants under 17 months of age who have completed three doses of commercially available DPT-IPV, Hib vaccine and HB vaccine were vaccinated a single intramuscular dose of KD2-396 as an additional vaccination. As a result, serious concerns about safety profile for KD2-396 was not observed and KD2-396 was considered as tolerable in clinical. KD2-396 was also shown to be capable of inducing antibodies against PT, FHA, diphtheria toxin, tetanus toxoid, attenuated poliovirus types 1, 2, 3, PRP and HBsAg.

Dec. 22, 2023

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031220411

Shinmura Yasuhiko

KM Biologics Co., Ltd.

1314-1 Kyokushi Kawabe, Kikuchi-shi, Kumamoto, Japan

rinkai-jrct@kmbiologics.com

Yamashita Masatoshi

KM Biologics Co., Ltd.

1314-1 Kyokushi Kawabe, Kikuchi-shi, Kumamoto, Japan

+81-968-37-4073

rinkai-jrct@kmbiologics.com

Complete

Nov. 08, 2022

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

prevention purpose

1)Subjects who received three doses of vaccine against pertussis, diphtheria, tetanus, acute poliomyelitis (polio), Haemophilus influenzae type b infection (Hib infection) and hepatitis B (as documented in the Maternal and Child Health Handbook)
2)Subjects who can receive the investigational product by 17 months of age
3)Subjects who obtain written informed consent from their legally acceptable representatives

1)Subjects with a medical history of pertussis, diphtheria, tetanus, acute poliomyelitis (polio), Hib infection, or hepatitis B (based on the interview of their legally acceptable representatives)
2)Subjects who have completed four doses of vaccine against pertussis, diphtheria, tetanus, acute poliomyelitis (polio) and Hib infection (as documented in the Maternal and Child Health Handbook)
3)Subjects who received hepatitis B vaccine and HBIG to prevent vertical transmission
4)Subjects who have exhibited anaphylaxis previously due to ingredients of the investigational product
5)Patients with fibrodysplasia ossificans progressive
6)Subjects who participated in another study and received other investigational products within past 4 months (120 days) from the date of the investigational product vaccination
7)Subjects with an interval of less than 6 months between the third vaccination of DPT-IPV and Hib vaccine and the investigational product vaccination
8)Subjects with an interval of less than 1 month between the third vaccination of hepatitis B vaccine and the investigational product vaccination
9)Subjects who are judged ineligible for participation in this study by the principal investigator or the subinvestigator

Both

Prevention of pertussis, diphtheria, tetanus, acute poliomyelitis, Hib infection and hepatitis B

Inoculate KD2-396 intramuscularly 0.5 mL per dose

<Immunogenicity>
-Geometric mean fold rise (GMFR) for PT, FHA, diphtheria toxin, tetanus toxoid, PRP, and HBsAg before and after the investigational product vaccination
-Mean difference in antibody titers (log2) against attenuated poliovirus types 1, 2, 3 before and after the investigational product vaccination
<Safety>
-The incidence and causal relationship to the investigational product of all adverse events, adverse events resulting in death, serious adverse events other than death, important adverse events, and severe (Grade 3 or higher) adverse events occurring up to 27 days after the investigational product vaccination
-The incidence, severity, number of days to onset, duration, and causal relationship to the investigational product of solicited local adverse events
-The incidence, severity, number of days to onset, duration, and causal relationship to the investigational product of solicited systemic adverse events
-The incidence, severity, number of days to onset, duration, and causal relationship to the investigational product of unsolicited adverse events
-Maximum body temperature from vaccination of the investigational product to 6 days after the investigational product vaccination

-Prevalence of antibodies above the protective threshold against PT, FHA, diphtheria toxin, tetanus toxoid, attenuated poliovirus types 1, 2, 3, PRP, and HBsAg after the investigational product vaccination
-Geometric mean antibody titers (hereafter GMT) against PT, FHA, diphtheria toxin, tetanus toxoid PRP, and HBsAg after the investigational product vaccination
-Mean antibody titers (log2) against attenuated poliovirus types 1, 2, 3 after the investigational product vaccination

+81-3-6779-8166

Oct. 13, 2022

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