臨床研究等提出・公開システム

A randomized, controlled, blinded study of ARCT-2301 as booster in healthy adults in Japan (Phase III)

ARCT-2301 Phase III Study

930

Of 923 subjects in the FAS, 856 (92.7%) were >=18 to <65 years and 67 (7.3%) were >=65 years of age, and 217 (23.5%) were >=60 years and 565 (61.2%) were >=50 years of age. A total of 445 (48.2%) participants were male and 478 (51.8%) were female.

Of 930 subjects who were randomized and exposed, 923, 804 and 914 subjects were included in the FAS, PPS-1, and PPS-2, respectively. One subject who received 2 doses of the study vaccine was excluded from all analysis sets. For the analysis of neutralizing antibody titers up to Day 181, a modified version of the PPS-1 was used, which was termed PPS-1-ic. This set excluded immunogenicity data from those subjects who had positive results from the nucleocapsid-specific antibody test at the given time point being assessed and all subsequent timepoints.

-Solicited local AEs (>=Grade 1) were reported in 439 subjects (94.8%) in the ARCT-2301 group and 441 subjects (95.0%) in the COMIRNATY (BA.4/5) group. The most commonly reported solicited local AE (>=Grade 1) was injection site tenderness (430 subjects [92.9%] in the ARCT-2301 group and 427 subjects [92.0%] in the COMIRNATY [BA.4/5] group), followed by injection site pain (379 subjects [81.9%] in the ARCT-2301 group and 378 subjects [81.5%] in the COMIRNATY [BA.4/5] group) in both groups. Solicited local AEs of grade 3 or higher were reported in 2 subjects (0.4%) in the COMIRNATY (BA.4/5) group, while no solicited local AEs of grade 3 or higher were reported in the ARCT-2301 group. -Solicited systemic AEs (>=Grade 1) were reported in 257 subjects (55.5%) in the ARCT-2301 group and 234 subjects (50.4%) in the COMIRNATY (BA.4/5) group. The most commonly reported solicited systemic AE (>=Grade 1) was malaise in both groups (177 subjects [38.2%] in the ARCT-2301 group and 157 subjects [33.8%] in the COMIRNARY [BA.4/5] group). Solicited systemic AEs of grade 3 or higher were reported in 5 subjects (1.1%) in the ARCT-2301 group and 6 subjects (1.3%) in the COMIRNATY (BA.4/5) group. -Unsolicited AEs (any grade) were reported in 73 subjects (15.8 %) in the ARCT-2301 group and 83 subjects (17.9%) in the COMIRNATY (BA.4/5) group. Most common (incidence of 1% or higher; i.e., 5 or more subjects in either group) unsolicited AE (any grade) related to the study vaccinate (by PT) in the ARCT-2301 group and the COMIRNATY (BA.4/5) group was injection site pruritus (3 subjects [0.6%] and 10 subjects [2.2 %], respectively) (Table 14.3.6-2_Day181). The reported AEs of injection site pruritus were all related to the study vaccine. -Featured symptoms (chest pain and shortness of breath) were collected in all subjects for early detection of AEs of special interest (myocarditis and pericarditis). In the ARCT-2301 group, chest pain was reported in 2 subjects (0.4%) and shortness of breath was reported in 1 subject (0.2%) within 7 days after vaccination. In the COMIRNATY (BA.4/5) group, chest pain was reported in 2 subjects (0.4%) and shortness of breath was reported in 1 subject (0.2%) within 7 days after vaccination. All the reported featured symptoms were assessed as related to the study vaccine by the investigators. For all cases of featured symptoms, the possibility of myocarditis or pericarditis was excluded following evaluation by the investigators or a cardiologist. -From Day 1 to Day 29, there was 1 SAE reported in 1 subject (0.2%) in the ARCT-2301 group and 1 SAE reported in 1 subject (0.2%) in the COMIRNATY (BA.4/5) group. Between Day 29 and Day 181, there was 1 SAE reported in 1 subject (0.2%) in the ARCT-2301 group and 3 SAEs reported in 3 subjects (0.6%) in the COMIRNATY (BA.4/5) group. Of the 6 SAEs, 4 were resolved, and 2 were resolving. All SAEs were assessed by investigators as not related to the study vaccines. -No AEs of special interest or AEs leading to discontinuation/dropout were reported up to Day 181.

Primary and secondary objectives were met. Primary endpoint -The GMT ratio of neutralizing antibodies against SARS-CoV-2 (Omicron strain BA.4/5) of ARCT-2301 compared with COMIRNATY (BA.4/5) was 1.49 (95% CI: 1.26, 1.76) on Day 29. Since the lower limit of the 95% CI exceeded the predefined non-inferiority margin of 0.67, the non-inferiority of ARCT-2301 to COMIRNATY (BA.4/5) was confirmed. -The difference in SRR of neutralizing antibodies against SARS-CoV-2 (Omicron strain BA.4/5) of ARCT-2301 and COMIRNATY (BA.4/5) was 7.2% (95% CI: 0.6, 13.7) on Day 29. Since the lower limit of the 95% CI exceeded the predefined non-inferiority margin of -10%, the non-inferiority of ARCT-2301 to COMIRNATY (BA.4/5) was confirmed. Secrondary endpoint -The GMT ratio and the difference in SRR of neutralizing antibodies against SARS-CoV-2 (Wuhan strain) of ARCT-2301 compared with COMIRNATY (BA.4/5) were 1.45 (95% CI: 1.28, 1.63) and 12.5% (95% CI: 5.9, 19.0), respectively, on Day 29. Since each lower limit of the 95% CI for GMT ratio and SRR difference exceeded the predefined non-inferiority margin of 0.67 and -10%, respectively, the non-inferiority of ARCT-2301 to COMIRNATY (BA.4/5) was confirmed. -Since the non-inferiority of ARCT-2301 to COMIRNATY (BA.4/5) was confirmed for both SARS-CoV-2 (Omicron strain BA.4/5 and Wuhan strain) on Day 29, superiority for the GMT and SRR of neutralizing antibodies against SARS-CoV-2 (Omicron strain BA.4/5) on Day 29 was evaluated. Since each lower limit of the 95% CI for GMT ratio and SRR difference exceeded the predefined superiority margins of 1.0 and 0%, the superiority of ARCT-2301 to COMIRNATY (BA.4/5) was confirmed.

The immunogenicity of ARCT-2301 was non-inferior to COMIRNATY (BA.4/5) against SARS-CoV-2 (Omicron BA.4/5 and Wuhan), and meeting the primary objective of the study. The immunogenicity against SARSCoV-2 (Omicron BA.4/5 and Wuhan) of ARCT-2301 was confirmed to be superior to that of COMIRNATY (BA.4/5). No safety concerns were raised from the study. The results of the study support the favorable benefit/risk profile of the ARCT-2301 vaccine when administered as a booster dose in adult subjects.

Jan. 14, 2025

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031230340

Yusuke Okada

Meiji Seika Pharma Co.,Ltd.

2-4-16, Kyobashi, Chuo-ku, Tokyo

clinical-trials@meiji.com

Clinical Development Dept.

Meiji Seika Pharma Co.,Ltd.

2-4-16, Kyobashi, Chuo-ku, Tokyo

+81-3-3273-3746

clinical-trials@meiji.com

Complete

Sept. 30, 2023

Interventional

randomized controlled trial

double blind

active control

parallel assignment

treatment purpose

1) Individuals are participant (irrespective of gender) >=18 years of age at Informed consent.
2) Participant or legally authorized representatives must freely provide documented informed consent prior to study procedures being performed.
3) Individuals must have been previously vaccinated with mRNA COVID-19 vaccine and satisfy the following criteria.
- Received 2~4 doses with authorized mRNA COVID-19 vaccine (monovalent COMIRNATY or monovalent SPIKEVAX)
- Received the last booster dose of COMIRNATY RTU intramuscular injection ([bivalent: Wuhan strain/Omicron BA.1] or [bivalent: Wuhan strain/Omicron BA.4/5])
- At least 3 months have passed since the last vaccination at the time of screening
- Receipt of these vaccines is supported by any documents and application software

1) Individuals with acute medical illness or febrile illness, including oral temperature >= 37.5 degree Celsius within 1 day prior to Screening. These individuals may be offered the opportunity to enter the study after fever and illness has stabilized. Participants with suspected or confirmed COVID-19 should be excluded and referred for medical care. Rescreening will be permitted for individuals who presented with suspected COVID-19 if another cause is confirmed.
2) Individuals with a positive SARS-CoV-2 rapid antigen test at Screening
3) Individuals with a history of COVID-19 with ongoing sequelae of COVID-19 infection within 6 months
sequelae.

Both

Prevention of SARS-CoV-2 infection

ARCT-2301: Administer 0.5 mL (5 micro g) as a single intramuscular injection.
COMIRNATY (BA.4-5) : Administer 0.3 mL (30 micro g) as a single intramuscular injection.

SARS-CoV-2, COVID-19

Geometric mean titer (GMT) and Seroresponse rate (SRR) of neutralizing antibodies against SARS-CoV-2 (Omicron strain BA.4-5) on Day 29

+81-3-6779-8166

none