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A Phase 2/3, Randomized, Active-controlled, Observer-blinded, Non-inferiority Study to Evaluate the Safety and Immunogenicity of Booster Immunization with DS-5670a/b (Bivalent: Original Strain/Omicron Strain BA.4-5) in Subjects Aged 5 to 11 Years Who Have Completed Initial Immunization with Comirnaty Intramuscular Injection (Univalent: Original Strain)

A Phase 2/3, Randomized, Active-controlled, Observer-blinded, Non-inferiority Study to Evaluate the Safety and Immunogenicity of Booster Immunization with DS-5670a/b (Bivalent: Original Strain/Omicron Strain BA.4-5) in Subjects Aged 5 to 11 Years Who Have Completed Initial Immunization with Comirnaty Intramuscular Injection (Univalent: Original Strain)

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Part 1: The investigational drug was administered to 7 participants (4 participants in the DS-5670a/b 10 ug group and 3 participants in the DS-5670a/b 20 ug group). The mean age (standard deviation) of the 7 participants was 8.6 (1.92) years. There were 6 females(85.7%) and 1 male(14.3%). Part 2: A total of 155 participants (76 in the DS-5670a/b 20 ug group and Comirnaty group: 79 participants) were randomized, and the investigational drug was administered to 154 participants except for 1 participant in the DS-5670a/b 20 ug group. The mean age (standard deviation) of the 149 participants included in the Immunogenicity Evaluable PPS in Part 2 was 8.8 (1.86) years.There were 73 males (49.0%). The median (range) interval between the second Comirnaty intramuscular injection for ages 5 - 11 years (monovalent: strain of origin) and administration of the investigational drug was 13.80 (3.9 - 18.8) months. The proportion of participants with a history of SARS-CoV-2 infection was 47.7% (71/149). No apparent differences between treatment groups were observed in the main demographic characteristics and baseline characteristics of the Immunogenicity Evaluable PPS in Part 2. The main demographic characteristics and baseline characteristics of other analyzable populations were similar to those of the Immunogenicity Evaluable PPS.

Part 1: 7 participants who completed tInitial Immunization with Comirnaty (4 in the DS-5670a/b 10 ug group and 3 in the DS-5670a/b 20 ug group) received the investigational drug, and all were included in the safety analysis population and the specific safety analysis population. Part 2: Of the 155 randomized participants (76 in the DS-5670a/b group and 79 in the Comirnaty group), 154 (75 in the DS-5670a/b group and 79 in the Comirnaty group) were enrolled in the FAS after excluding 1 participant (1 in the DS-5670a/b group) who did not receive the investigational drug. Among the FAS, 150 participants (74 men, 76 women) were enrolled in the PPS, excluding 1 participant in the DS-5670a/b group and 3 participants in the Comirnaty intramuscular injection group who had serious protocol violations that could affect the efficacy evaluation. Among the FAS,153 participants (75 in the DS-5670a/b group, 78 in the Comirnaty group) were included in the Immunogenicity Evaluable FAS, excluding 1 participant in the Comirnaty group who did not have available immunogenicity measurements at Day 29. Among the Immunogenicity Evaluable FAS,149 participants (74 in the DS-5670a/b group, 75 in the Comirnaty group) were enrolled in the Immunogenicity Evaluable PPS, excluding 1 participant in the DS-5670a/b group and 3 participants in the Comirnaty group who had serious protocol violations that affected immunogenicity assessment.

Part 1: The number of participants who experienced solicited injection site adverse events was 4 in the DS-5670a/b 10 ug group and 3 in the DS-5670a/b 20 ug group. No severe solicited injection site adverse events were observed. The number of participants who experienced solicited systemic adverse events was 2 in the DS-5670a/b 10 ug group and 1 in the DS-5670a/b 20 ug group. No severe solicited systemic adverse events were observed in the DS-5670a/b 10 ug group, and one case was observed in the DS-5670a/b 20 ug group. The number of subjects who experienced unsolicited adverse events was 2 in the DS-5670a/b 10 ug group and 2 in the DS-5670a/b 20 ug group. No severe unsolicited adverse events were observed. No adverse events or seriouse adverse events leading to death, or adverse events resulting in discontinuation of the investigational drug or termination of the trial were observed. No major safety concerns were identified at either the 10 ug or 20 ug dose of DS-5670a/b, and tolerability was observed. Part 2: The incidence rate of solicited adverse events (injection site and systemic) was 88.0% (66/75) in the DS-5670a/b group and 91.1% (72/79) in the Comirnaty group. The incidence rate of solicited injection site adverse events was 86.7% (65/75) in the DS-5670a/b group and 88.6% (70/79) in the Comirnaty group, and the incidence rate of solicited systemic adverse events was 37.3% (28/75) in the DS-5670a/b group and 29.1% (23/79) in the Comirnaty group.Severe solicited injection site adverse events were observed in 2.7% (2/75) of the DS-5670a/b group and were not observed in the Comirnaty group. The incidence rate of severe solicited systemic adverse events was 4.0% (3/75) in the DS-5670a/b group and 1.3% (1/79) in the Comirnaty group. The incidence rate of unsolicited adverse events was 48.0% (36/75) in the DS-5670a/b group and 41.8% (33/79) in the Comirnaty group. No severe unsolicited adverse events were observed. No adverse events or seriouse adverse events leading to death, or adverse events resulting in discontinuation of the investigational drug or termination of the trial were observed.

Part 2: - The ratio of adjusted GMT of serum anti-SARS-CoV-2 (Omicron strain BA.5.2.1) neutralizing activity 4 weeks after investigational drug administration (Day 29) (DS-5670a/b group/Comirnaty intramuscular injection group) (95% confidence interval) was 1.636 (1.221 to 2.190), and the difference in adjusted immune response rates (DS-5670a/b group - Comirnaty intramuscular injection group) (95% confidence interval) was 2.6 (-7.8 to 13.8)%. Both met the non-inferiority criteria in this clinical trial, confirming the non-inferiority of DS-5670a/b compared to Comirnaty intramuscular injection. - The ratio of adjusted GMT of serum anti-SARS-CoV-2 (original strain) neutralizing activity 4 weeks after administration of the investigational drug (Day 29) (95% confidence interval) was 1.105 (0.843 to 1.448), and the difference in adjusted immune response rate (95% confidence interval) was -4.4 (-17.1 to 8.8)%. An increase in serum anti-SARS-CoV-2 (original strain) neutralizing activity was observed following the DS-5670a/b booster dose, with GMTs higher than those in the Comirnaty intramuscular injection group. Additionally, the immune response rate in the DS-5670a/b group was comparable to that in the Comirnaty intramuscular injection group. - No cases of COVID-19 were observed in either treatment group from 7 days after administration of the investigational drug until 4 weeks later (Day 29). - At 4 weeks after investigational drug administration (Day 29), the GMT of serum anti-SARS-CoV-2 (Omicron strain BQ.1.1.3) neutralizing activity increased from baseline in both treatment groups, with values of 900.376 in the DS-5670a/b group and 982.676 in the Comirnaty group, and were comparable between treatment groups.The immune response rate 4 weeks after administration of the investigational drug (Day 29) was 88.1% in the DS-5670a/b group and 89.8% in the Comirnaty group, with no significant difference between treatment groups. - The GMT of serum anti-SARS-CoV-2 (Omicron strain XBB.1.5.6) neutralizing activity 4 weeks after administration of the investigational drug (Day 29) increased from baseline in both treatment groups, with values of 783.048 in the DS-5670a/b group and 488.448 in the Comirnaty group, DS-5670a/b group was higher than that in the Comirnaty group. The immune response rate 4 weeks after administration of the investigational drug (Day 29) was 95.5% in the DS-5670a/b group and 86.4% in the Comirnaty group, with the DS-5670a/b group showing a higher rate than the Comirnaty group. - Regarding the neutralizing activity of serum anti-SARS-CoV-2 (Omicron strain BA.5.2.1) 4 weeks after administration of the investigational drug (Day 29), by sex and history of SARS-CoV-2 infection,there were no significant differences in the GMT ratio of the DS-5670a/b group compared to the Comirnaty group or in the difference in immune response rates between the DS-5670a/b group and the Comirnaty group, no significant differences were observed in either subgroup compared to the overall population. When stratified by the interval between the second dose of the Comirnaty intramuscular injection for ages 5 - 11 (monovalent: original strain) and the investigational drug administration, the subgroup with an interval of 3 months or more but less than 6 months had only 7 eligible participants in the overall population, making it difficult to evaluate the results.

In Part 2, the study enrolled participants aged 5 to 11 years who had completed the initial immunization with Comirnaty, DS-5670a/b at the dose determined in Part 1 (20 ug) or Comirnaty was administered intramuscularly. At 4 weeks after the booster dose (Day 29) following administration of DS-5670a/b, the neutralizing activity against SARS-CoV-2 (Omicron strain BA.5.2.1) was non-inferior to Comirnaty. Regarding safety, no significant differences were observed between DS-5670a/b and Comirnaty.

Sept. 02, 2024

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1445459/full

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031220665

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

May. 09, 2023

Interventional

randomized controlled trial

double blind

active control

parallel assignment

prevention purpose

1) Subjects aged 5 to 11 years at the time of informed consent.
2) Having provided written consent to study participation via the legal representative.
3)Having completed initial immunization with Comirnaty IM in the past, with at least 3 months elapsed since the 2nd dose.
4) Able to comply with the rules of the study, undergo physical examinations and tests that are specified in the protocol, and report symptoms or other issues.

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 for SARS-CoV-2 infection (based on reverse transcription polymerase chain reaction [RT-PCR], other nucleic acid detection methods, or SARS-CoV-2 antigen test) within 3 months before informed consent, or having been diagnosed with coronavirus disease 2019 (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 antibody test at the time of eligibility evaluation, with symptoms suspected of SARS-CoV-2 infection (eg, respiratory symptoms, headache, malaise, anosmia, dysgeusia, pharyngeal pain) within 3 months before informed consent.

Both

Prevention of infectious disease by Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)

A dose of either DS-5670a/b or Comirnaty IM will be intramuscularly administered to the deltoid muscle of the upper arm.

GMT of blood neutralizing activity against SARS-CoV-2 (Omicron strain BA.5) and seroresponse rate at 4 weeks after study drug administration

Efficacy
- GMT of blood neutralizing activity against SARS-CoV-2 (original strain) and seroresponse rate at 4 weeks after study drug administration
- Incidence of COVID-19 for 52 weeks after study drug administration

Safety
Solicited adverse events (injection site and systemic), Unsolicited adverse events, Serious adverse events, Laboratory values for 28 days after study drug administration

+81-3-5366-3006

April. 12, 2023

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