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A Phase 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 12 Years and Older Who Have Completed Initial and Booster Immunization with SARS-CoV-2 Vaccines

A Phase 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 12 Years and Older Who Have Completed Initial and Booster Immunization with SARS-CoV-2 Vaccines

1403

In Main Study, a total of 701 participants were randomized, with 349 in the DS-5670a/b group and 352 in the Comirnaty RTU intramuscular injection group and administered the investigational product. The average (standard deviation [SD] ) age of participants in the DS-5670a/b group was 53.9 (13.43) years old, with 200 males (57.3%) and 149 females (42.7%). The average (standard deviation [SD] ) age of participants in the Comirnaty RTU intramuscular injection group was 54.1 (13.13) years old, with 215 males (61.1%) and 137 females (38.9%). In Sub Study A, a total of 301 participants were randomized, with 74 in the DS-5670a/b 60 ug group, 75 in the DS-5670a 60 ug group, 77 in the DS-5670b 30 ug group, and 75 in the DS-5670b 60 ug group and administered the investigational product. The average (standard deviation [SD] ) age of participants in the DS-5670a/b 60 ug group was 47.2 (13.52) years old, with 34 males (45.9%) and 40 females (54.1%). The average (standard deviation [SD] ) age of participants in the DS-5670a 60 ug group was 44.5 (14.95) years old, with 38 males (50.7%) and 37 females (49.3%). The average (standard deviation [SD] ) age of participants in the DS-5670b 30 ug group was 47.1 (14.51) years old, with 37 males (48.1%) and 40 females (51.9%). The average (standard deviation [SD] ) age of participants in the DS-5670b 60 ug group was 49.2 (13.24) years old, with 37 males (49.3%) and 38 females (50.7%). In Sub Study B, a total of 401 participants were randomized in the DS-5670a/b group and administered the investigational product. The average (standard deviation [SD] ) age of participants in the DS-5670a/b group was 47.9 (16.44) years old, with 215 males (53.6%) and 186 females (46.4%).

In Main Study, randomised 701 participants, with 349 in the DS-5670a/b group and 352 in the Comirnaty RTU intramuscular injection group were included in the Full Analysis Set (FAS). One participant in the DS-5670a/b group was excluded from the Per Protocol Set (PPS). In Sub Study A, randomised 301 participants, with 74 in the DS-5670a/b 60 ug group, 75 in the DS-5670a 60 ug group, 77 in the DS-5670b 30 ug group, and 75 in the DS-5670b 60 ug group were included in both the Full Analysis Set (FAS) and Per Protocol Set (PPS). In Sub Study B, randomised 401 participants in the DS-5670a/b group were included in the Full Analysis Set (FAS). 2 participants in the DS-5670a/b group was excluded from the Per Protocol Set (PPS).

1) Main Study -The incidence of solicited injection site adverse events was 89.4% (312/349) in the DS-5670a/b group and 86.9% (306/352) in the Comirnaty RTU intramuscular injection group. The incidence of solicited systemic adverse events was 43.0% (150/349) in the DS-5670a/b group and 48.3% (170/352) in the Comirnaty RTU intramuscular injection group. -The incidence of solicited injection site adverse events was not different significantly between the DS-5670a/b group and the Comirnaty RTU intramuscular injection group. The most commonly observed solicited injection site adverse events in both groups were injection site pain and injection site warmth. -The incidence of solicited systemic adverse events was not different significantly between the DS-5670a/b group and the Comirnaty RTU intramuscular injection group. The most commonly observed solicited systemic adverse events in both groups were malaise and headache. -The most commonly observed severe solicited injection site adverse events in the DS-5670a/b group was injection site pain, while in the Comirnaty RTU intramuscular injection group, injection site pain and injection site warmth. The other solicited injection site adverse events were mild or moderate. -The most commonly observed severe solicited systemic adverse events in the DS-5670a/b group was fever, while in the Comirnaty RTU intramuscular injection group, malaise. The other solicited systemic adverse events were mild or moderate. -The incidence of unsolicited adverse events was not different significantly between the DS-5670a/b group and the Comirnaty RTU intramuscular injection group. The most commonly observed unsolicited adverse events in the DS-5670a/b group were nasopharyngitis, fever, COVID-19, diarrhea and injection site erythema. Among of them, fever, diarrhea and injection site erythema were considered to be related to the investigational product. -The incidence of delayed injection site adverse events was 1.4% (5/349) in the DS-5670a/b group and 0.3% (1/352) in the Comirnaty RTU intramuscular injection group. The incidence of delayed systemic adverse events was 0.6% (2/349) in the DS-5670a/b group and 0.9% (3/352) in the Comirnaty RTU intramuscular injection group. -Diarrhea, inguinal hernia, injection site erythema and injection site swelling were observed in the DS-5670a/b group as the severe unsolicited adverse events. No severe unsolicited adverse events were observed in the Comirnaty RTU intramuscular injection group. Among of them, diarrhea, injection site erythema and injection site swelling were considered to be related to the investigational product. Injection site erythema and injection site swelling were considered as delayed injection site adverse events. Diarrhea, injection site erythema and injection site swelling were recovered. Inguinal hernia was also recovered during follow-up period. 2) Sub Study A -The incidence of solicited injection site adverse events was 90.5% (67/74) in the DS-5670a/b 60 ug group, 89.3% (67/75) in the DS-5670a 60 ug group, 87.0% (67/77) in the DS-5670b 30 ug group, and 89.3% (69/75) in the DS-5670b 60 ug group. The incidence of solicited systemic adverse events was 48.6% (36/74) in the DS-5670a/b 60 ug group, 52.0% (39/75) in the DS-5670a 60 ug group, 44.2% (34/77) in the DS-5670b 30 ug group, and 49.3% (37/75) in the DS-5670b 60 ug group. -The incidence of solicited injection site adverse events was not different significantly between these groups. -The incidence of solicited systemic adverse events was not different significantly between these groups. -The incidence of severe solicited injection site adverse events was not different significantly between these groups. All these events were recovered. -The incidence of severe solicited systemic adverse events was not different significantly between these groups. All these events were recovered. 3) Sub Study B -Clavicle fracture was observed with one participant as severe adversed event. The severity of this event is moderate. This event was considered not to be related to the investigational product due to the accidental traffic accident. The outcome was recovering.

1) Main Study -The ratio of the adjusted geometric mean titer (GMT) of anti-SARS-CoV-2 (Omicron variant BA.5.2.1) neutralizing activity in the blood at 4 weeks after the administration of the investigational product (Day 29) between the DS-5670a/b group and the Comirnaty RTU intramuscular injection group (95% confidence interval) was 1.720 (1.516 - 1.952), and the difference in immunological response rates (DS-5670a/b group - Comirnaty RTU intramuscular injection group) (95% confidence interval) was 21.6 (14.0 - 28.8)%. Both met the non-inferiority criteria in this clinical trial, confirming the non-inferiority of DS-5670a/b compared to Comirnaty RTU intramuscular injection. -The ratio of the adjusted GMT of anti-SARS-CoV-2 (original strain) neutralizing activity in the blood at 4 weeks after the administration of the investigational product (Day 29) (95% confidence interval) was 1.893 (1.707 - 2.100), and the difference in immunological response rates (95% confidence interval) was 30.9 (23.6 - 37.7)%. An increase in anti-SARS-CoV-2 (original strain) neutralizing activity due to the additional dose of DS-5670a/b was confirmed, showing higher GMT and immunological response rates compared to the Comirnaty RTU intramuscular injection group. -There was no significant difference in the incidence of COVID-19 between the groups from 7 days after the administration of the investigational product through to 4 weeks later (Day 29). -Regarding the neutralizing activity of anti-SARS-CoV-2 (Omicron variant BA.5.2.1) in the blood at 4 weeks after the administration of the investigational product (Day 29) by subgroup (age, interval since last vaccination, gender, vaccination history, age, and vaccination history), no significant differences were observed in the ratio of GMT between the DS-5670a/b group and the Comirnaty RTU intramuscular injection group, nor in the difference in immunological response rates between the DS-5670a/b group and the Comirnaty RTU intramuscular injection group within any of the subgroups. 2) Sub Study A Not Applicable 3) Sub Study B Not Applicable

It was confirmed that the anti-SARS-CoV-2 (Omicron variant BA.5.2.1) neutralizing activity in the blood at 4 weeks after the additional immunization with DS-5670a/b 60 ug (Day 29) was non-inferior to that of the control vaccine, Comirnaty RTU intramuscular injection. Regarding safety, no significant differences were observed between the groups receiving DS-5670a/b 60 ug and those receiving Comirnaty RTU intramuscular injection.

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https://jrct.mhlw.go.jp/latest-detail/jRCT2071220111

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

Main Study:
1) Subjects aged 12 years and older at the time of informed consent.
2) Having provided written consent to study participation (by the subject or via his/her legal representative).
3) Having completed initial immunization with Comirnaty IM and booster immunization with Comirnaty RTU IM or having completed booster immunization with Comirnaty RTU IM after receiving initial and booster immunization with Comirnaty IM in the past, with at least 3 months elapsed since the last booster dose of Comirnaty RTU IM.
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 (reporting by the legal representative is also acceptable).
Sub Study A:
1) Subjects aged 12 years and older at the time of informed consent.
2) Having provided written consent to study participation (by the subject or via his/her legal representative).
3) Having completed initial and booster immunization with Comirnaty IM in the past, with at least 3 months elapsed since the last booster 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 (reporting by the legal representative is also acceptable).
Sub Study B:
1) Subjects aged 12 years and older at the time of informed consent.
2) Having provided written consent to study participation (by the subject or via his/her legal representative).
3) Having completed initial immunization with approved SARS-CoV-2 vaccines (Comirnaty IM or Spikevax IM) and booster immunization with approved SARS-CoV-2 vaccines (Comirnaty IM, Comirnaty RTU IM [bivalent: original strain/Omicron strain BA.1, or bivalent: original strain/Omicron strain BA.4-5], Spikevax IM [univalent: original strain, bivalent: original strain/Omicron strain BA.1, or bivalent: original strain/Omicron strain BA.4-5], or Nuvaxovid IM) or DS-5670a in the past, with at least 3 months elapsed since the last booster 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 (reporting by the legal representative is also acceptable).

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 in the past (in the case of Sub Study B, 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.

Both

Prevention of infection due to SARS-CoV-2

A dose of either DS-5670a/b (60ug), DS-5670a (60ug), DS-5670b (60ug or 30ug), or Comirnaty RTU IMA (30ug) will be intramuscularly administered to the deltoid muscle of the upper arm.

Main Study:
Geometric mean titer (GMT) of blood neutralizing activity against SARS-CoV-2 (Omicron strain BA.5) and seroresponse rate at 4 weeks after study drug administration
Sub Study A, Sub Study B: Not applicable.

Efficacy
Main Study:
- 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
Sub Study A, Sub Study B: Not applicable.

Safety
Main Study, Sub Study B: Solicited adverse events (injection site and systemic), Unsolicited adverse events, Serious adverse events
Sub Study A: Solicited adverse events (injection site and systemic), Unsolicited adverse events, Serious adverse events, Laboratory values for 28 days after study drug administration

+81-92-283-7701

Mar. 09, 2023

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