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A phase III, randomized, active-comparator, observer-blind, non-inferiority study to demonstrate the immunogenicity and safety of DS-5670d (monovalent: omicron XBB.1.5) in adults and children aged 12 years and older

A phase III, randomized, active-comparator, observer-blind, non-inferiority study to demonstrate the immunogenicity and safety of DS-5670d(monovalent: omicron XBB.1.5) in adults and children aged 12 years and older

779

The mean age (standard deviation) of the 777 participants administered the investigational drug (393 in the DS-5670d group, 384 in the Comirnaty RTU IM group) was 43.6 (16.23) years. There were 64 participants (8.2%) aged 12 to under 18 years, 644 participants (82.9%) aged 18 to under 65 years, and 69 participants (8.9%) aged 65 years or older. There were 425 males (54.7%) and 352 females (45.3%). Among these, there were 286 participants (36.8%) with a history of SARS-CoV-2 infection and a history of SARS-CoV-2 vaccination (Sub-population A); 133 participants (17.1%) with a history of SARS-CoV-2 infection but no history of SARS-CoV-2 vaccination (Sub-population B); 330 participants (42.5%) with no SARS-CoV-2 infection history but had a history of SARS-CoV-2 vaccination (Sub-population C), and 28 participants (3.6%) with neither a history of SARS-CoV-2 infection nor a history of SARS-CoV-2 vaccination (Sub-population D).

Of the randomized 779 participants (394 in the DS-5670d group, 385 in the Comirnaty RTU IM group; the same applies hereafter), 777 (393, 384) received the investigational drug, excluding 2 (1, 1), and 23 (12 and 11, respectively) discontinued the trial by the end of the follow-up period. Of the 777 participants administered the investigational drug, 725 (362, 363) were included in the analysis of the primary endpoint, who had at least one of a history of SARS-CoV-2 infection or a history of SARS-CoV-2 vaccination, had immunogenicity assessed before and after investigational drug administration, and had no major protocol deviations that could affect the immunogenicity assessment. 777 participants administered the investigational drug were included in the analysis of safety.

The occurrence of solicited adverse events (injection site and systemic) up to 7 days after investigational drug administration, unsolicited adverse events (adverse events other than solicited adverse events) up to 28 days after investigational drug administration, and severe adverse events up to 26 weeks after investigational drug administration were as follows. No adverse events leading to discontinuation of study treatment or withdrawal from the study was observed. The incidence rate of solicited adverse events (injection site and systemic) was 92.9% (365/393) in the DS-5670d group and 90.6% (348/384) in the Comirnaty RTU IM group. The incidence rate of solicited injection site adverse events was 91.9% (361/393) in the DS-5670d group and 88.3% (339/384) in the Comirnaty RTU IM group; and that of solicited systemic adverse events was 46.6% (183/393) in the DS-5670d group and 46.9% (180/384) in the Comirnaty RTU IM group, with no apparent difference between treatment groups. The most common solicited injection site adverse events observed in both treatment groups were injection site pain (DS-5670d group 89.3% [351/393], Comirnaty RTU IM group 85.7% [329/384], same order below) and injection site warmth (29.3% [115/393], 31.5% [121/384]). Additionally, most common solicited systemic adverse events observed in both treatment groups were malaise (DS-5670d group 30.5% [120/393], Comirnaty RTU IM group 35.9% [138/384], same order below), headache (17.8% [70/393], 24.7% [95/384]), and myalgia (17.3% [68/393], 19.0% [73/384]). The incidence rate of severe solicited injection site adverse events was 3.6% (14/393) in the DS-5670d group and 3.1% (12/384) in the Comirnaty RTU IM group; and that of severe solicited systemic adverse events was 1.8% (7/393) in the DS-5670d group and 2.6% (10/384) in the Comirnaty RTU IM group. The incidence rate of unsolicited adverse events was 19.6% (77/393) in the DS-5670d group and 19.3% (74/384) in the Comirnaty RTU IM group, with no apparent difference in the overall or the each incidence rate between treatment groups. The most common unsolicited adverse events observed in both treatment groups were nasopharyngitis (DS-5670d group 3.8% [15/393], Comirnaty RTU IM group 2.1% [8/384]; the same applies hereafter), injection site erythema (2.3% [9/393], 0.3% [1/384]), injection site pain (1.5% [6/393], 0.3% [1/384]), and injection site pruritus (1.5% [6/393], 0%). Among these, nasopharyngitis (0.3% [1/393], 0%), injection site erythema (2.0% [8/393], 0.3% [1/384]), injection site pain (1.5% [6/393], 0.3% [1/384]), and injection site pruritus (1.5% [6/393], 0%) were adverse reactions. No severe unsolicited adverse events were observed in either treatment group. The incidence of serious adverse events was 0.8% (3/393) in the DS-5670d group and 1.6% (6/384) in the Comirnaty RTU IM group, with no apparent difference between treatment groups. No serious adverse events were observed in two or more subjects in any treatment group, and all events were judged to have no causal relationship with the investigational drug. All events resolved or improved except for one death. One death (event name: sudden death) occurred in the DS-5670d group. However, there was no reasonable basis to establish a causal relationship between this event and the investigational drug and given the possibility of an association with the underlying condition of type 2 diabetes, no causal relationship between this event and the investigational drug was determined.

The primary endpoint, the adjusted GMT for serum anti-SARS-CoV-2 (Omicron XBB.1.5.6) neutralizing activity 4 weeks after investigational drug administration (Day 29) (95% CI) in healthy males and females aged 12 years and older with either a history of SARS-CoV-2 infection or SARS-CoV-2 vaccination history (Sub-population A, B, and C), was 1691.877 in DS-5670d group and 1388.927 in Comirnaty RTU IM group, the adjusted GMT ratio (DS-5670d group/ Comirnaty RTU IM group) was 1.218 (1.059 - 1.401), and the difference in adjusted seroresponse rate (DS-5670d group - Comirnaty RTU IM group) (95% CI)was 4.5 (-0.70 to 9.71)%. The key secondary endpoint, the adjusted GMT for serum anti-SARS-CoV-2 (Omicron XBB.1.5.6) neutralizing activity 4 weeks after investigational drug administration (Day 29) (95% CI) in healthy males and females aged 12 years and older, regardless of SARS-CoV-2 infection history or SARS-CoV-2 vaccination history (Sub-population A, B, C, and D), was 1326.489 in DS-5670d group and 1119.097 in Comirnaty RTU IM group, the adjusted GMT ratio (DS-5670d group / Comirnaty RTU IM group) was 1.185 (1.025 to 1.371) (95% CI), and the difference in adjusted seroresponse rate (DS-5670d group - Comirnaty RTU IM group) (95% CI) was 3.7% (-1.39 to 8.87%).

In subjects with either a history of SARS-CoV-2 infection or vaccination history, and regardless of them, the non-inferiority of DS-5670d to the comparator was verified, with both the GMT ratio and the difference in seroresponse rate to the comparator group for blood neutralizing activity against SARS-CoV-2 (Omicron strain XBB.1.5.6) at 4 weeks after investigational drug administration being greater than the pre-specified margins. Furthermore, no new safety concerns were observed.

Oct. 13, 2025

https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004499

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031230424

Inoguchi Akihiro

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial_jp@daiichisankyo.com

Contact for Clinical Trial Information

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial_jp@daiichisankyo.com

Complete

Jan. 09, 2024

Interventional

randomized controlled trial

double blind

active control

parallel assignment

prevention purpose

1) Subjects aged 12 years and older at the time of informed consent.
2) Having provided written consent to study participation.
3) Able to comply with the rules of the study, record symptoms via electronic diary by himself/herself or his/her legal representative, undergo physical examinations and tests that are specified in the protocol, and report symptoms or other issues (report from his/her legal representative to be available).

1) Having any serious cardiovascular, renal, hepatic, blood, neuropsychiatric, developmental disorder, thrombocytopenia, or coagulopathy.
2) Having a medical history of vaccination-related convulsions or epilepsy.
3) Having a concurrent or medical history of myocarditis or pericarditis.
4) Having tested positive within 3 months before informed consent for SARS-CoV-2 infection (based on RT-PCR, other nucleic acid detection methods, or SARS-CoV-2 antigen test), or having been diagnosed with COVID-19 based on a physician's examination.
5) Having been diagnosed with immunodeficiency in the past or having a close relative with congenital immunodeficiency.
6) Having symptoms suspected of SARS-CoV-2 infection (eg, respiratory symptoms, headache, malaise, anosmia, dysgeusia, pharyngeal pain) at the time of informed consent.
7) Having tested positive for SARS-CoV-2 antigen test at the time of eligibility evaluation.
8) Having tested positive for SARS-CoV-2 antibody test at the time of eligibility evaluation, with symptoms suspected ofSARS-CoV-2 infection (eg, respiratory symptoms, headache, malaise, anosmia, dysgeusia, pharyngeal pain) within 3 months before informed consent.

Both

Prevention of infection due to SARS-CoV-2

A dose of either DS-5670d (0.6 mL) or Comirnaty RTU IM (0.3 mL) will be intramuscularly administered to the deltoid muscle of the upper arm.

- The GMT of blood neutralising activity against SARS-CoV-2 (Omicron XBB.1.5) at 4 weeks after the administration in adults and children aged 12 years and older with at least one of SARS-CoV-2 infection history and SARS-CoV-2 vaccination history.
- The seroresponse rate of blood neutralising activity against SARS-CoV-2 (Omicron XBB.1.5) at 4 weeks after the administration in adults and children aged 12 years and older with at least one of SARS-CoV-2 infection history and SARS-CoV-2 vaccination history.

- The GMT of blood neutralising activity against SARS-CoV-2 (Omicron XBB.1.5) at 4 weeks after the administration in adults and children aged 12 years and older regardless of SARS-CoV-2 infection history and SARS-CoV-2 vaccination history.
- The seroresponse rate of blood neutralising activity against SARS-CoV-2 (Omicron XBB.1.5) at 4 weeks after the administration in adults and children aged 12 years and older regardless of SARS-CoV-2 infection history and SARS-CoV-2 vaccination history.

+81-3-5773-5570

Nov. 08, 2023

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