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A Phase III, Multicenter, Open-Label, Parallel-Group, Comparative Study to Evaluate the Immunogenicity and Safety of CSL402 (Self-Amplifying mRNA COVID-19 Vaccine) in Subjects Aged 12 Years or Older

CSL402 Phase III Study

579

A total of 579 subjects received the study vaccination. Of these, 148 children (12 to 17 years of age) and 431 adults (18 years of age or older). The median age of child subjects was 15.0 years (minimum of 12 years and maximum of 17 years), while that of adult subjects was 50.0 years (minimum of 18 years and maximum of 86 years). Overall, 331 subjects (57.2%) (77 children (52.0%) and 254 adults (58.9%)) were male and 248 subjects (42.8%) (71 children (48.0%) and 177 adults (41.1%)) were female.

A total of 625 healthy volunteers gave informed consent and were enrolled into the study. Of 625 enrolled subjects (149 children and 476 adults), 608 subjects met eligibility criteria, and 148 subjects in the child group and 431 subjects in the adult group received the study vaccine. Overall, 147 subjects in the child group and 429 subjects in the adult group completed the Day 29 assessments after administration of the study vaccine. One subject in the child group and 2 subjects in the adult group discontinued the study before Day 29. The reason for discontinuation for all 3 subjects was a request for withdrawal from the study by the subject or legally acceptable representative. A total of 144 subjects in the child group and 425 subjects in the adult group completed the Day 181 visit. In total, 4 subjects in the child group and 6 subjects in the adult group discontinued the study before Day 181 visit. The most common reason for discontinuation in both groups was a request for withdrawal from the study by the subject or legally acceptable representative. Of 579 (148 children and 431 adults) subjects who received the study vaccine, 572 (147 children and 425 adults) and 564 (146 children and 418 adults) subjects were included in the full analysis set (FAS) and the per protocol set (PPS), respectively.

A total of 579 subjects (148 in the child group and 431 in the adult group) were included in the analysis set for safety. - Solicited local AEs (>= Grade 0) were reported in 144 subjects (97.3%) in the child group and 403 subjects (93.5%) in the adult group. The most commonly reported solicited local AE was injection site tenderness (143 subjects (96.6%) in the child group and 388 subjects (90.0%) in the adult group), followed by injection site pain (132 subjects (89.2%) in the child group and 354 subjects (82.1%) in the adult group) in both groups. Solicited local AEs of Grade 3 were reported in 3 subjects (2.0%) in the child group and 3 subjects (0.7%) in the adult group. - Solicited systemic AEs (>= Grade 0) were reported in 129 subjects (87.2%) in the child group and 261 subjects (60.6%) in the adult group. The most commonly reported solicited systemic AE (Day 1 to Day 7; >= Grade 0) in the child group was pyrexia (103 subjects (69.6%)), followed by headache (83 subjects (56.1%)), while in the adult group it was malaise (167 subjects (38.7%)), followed by headache (119 subjects (27.6%)). Solicited systemic AEs of Grade 3 were reported in 14 subjects (9.5%) in the child group and 11 subjects (2.6%) in the adult group. - Common (incidence of 2% or higher in either group) unsolicited AEs (by PT) in the child group and the adult group were injection site pain (8 subjects (5.4%) and 16 subjects (3.7%), respectively), nasopharyngitis (8 subjects (5.4%) and 13 subjects (3.0%)), influenza (6 subjects (4.1%)) and 3 subjects (0.7%)), and malaise (4 subjects (2.7%) and 4 subjects (0.9%)). - In the child group, no chest pain was reported, while shortness of breath was reported in 1 subject (0.7%) within 7 days after vaccination. The reported featured symptom was considered related to the study vaccine by the investigator. In the adult group, chest pain was reported in 2 subjects (0.5%) within 7 days after vaccination, while no shortness of breath was reported. Chest pain in 1 subject was considered related to the study vaccine by the investigators, while chest pain in the other subject was considered not related to the study vaccine. For all cases of featured symptoms, the possibility of myocarditis or pericarditis was excluded following evaluation by the investigators or a cardiologist. - 1 subject (0.2%) in the adult group had a fatal SAE of malnutrition 113 days after receiving the study vaccine, assessed as not related to the study vaccines. - There were 2 SAEs (2 subjects) other than death reported in the child group (appendicitis and gastroenteritis viral) and 2 SAEs (2 subjects) other than death (large intestine polyp and meniscus injury) reported in the adult group. All of those SAEs were resolved and assessed by investigators as not related to the study vaccines. - No AEs of special interest, medically significant AEs, or AEs leading to discontinuation/dropout from the study excluding SAE were reported in either group by Day 181.

A total of 564 subjects (146 in the child group and 418 in the adult group) were included in the PPS, which was the primary analysis population for immunogenicity. Primary endpoint - The GMT of neutralizing antibody titers against SARS-CoV-2 (Omicron strain JN.1) on Day 29 was higher in the child group and the GMT ratio of children over adults was 1.79 (95% CI: 1.45, 2.21). Since the lower limit of the 95% CI exceeded the predefined non-inferiority margin of 0.67, the non-inferiority of GMT for children to adults was confirmed. Key secondary endpoint - The SRR of neutralizing antibody titers against SARS-CoV-2 (Omicron strain JN.1) on Day 29 was higher in the child group and the difference was 9.1% (95% CI: 2.9, 15.4). Since the lower limit of the 95% CI for SRR difference exceeded the predefined non-inferiority margin of -10%, the non-inferiority of SRR for children to adults was confirmed. Other secondary endpoints - The GMT of neutralizing antibody titers against SARS-CoV-2 (Omicron strain JN.1) gradually decreased from Day 29 to Day 181. The GMTs in the child group were higher than those in the adult group at all timepoints from Day 29 to Day 181. - The SRRs against SARS-CoV-2 (Omicron strain JN.1) gradually decreased from Day 29 to Day 181. The SRRs were higher in the child group than those in the adult group at all timepoints from Day 29 to Day 181. - The GMFR against SARS-CoV-2 (Omicron strain JN.1) on Day 29 was 18.80-fold (95% CI: 15.43, 22.90) in the child group and 15.40-fold (95% CI: 13.36, 17.76) in the adult group. The GMFRs against SARS-CoV-2 (Omicron strain JN.1) gradually decreased from Day 29 to Day 181. The GMFRs in the child group were higher than those in the adult group at all timepoints from Day 29 to Day 181.

The immunogenicity against SARS-CoV-2 (Omicron strain JN.1) in children was non-inferior to that in adults, thus meeting the primary objective of the study. Grade 3 systemic AEs were rare in both groups, with a slightly higher incidence of pyrexia in children. No safety concerns were raised from the study. The results of the study support the favorable benefit/risk profile of the CSL402 vaccine as a booster in adult subjects. In children, the CSL402 vaccine was immunogenic and well tolerated.

May. 15, 2026

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031240386

Minamida Takeshi

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

Oct. 22, 2024

Interventional

single arm study

open(masking not used)

uncontrolled control

parallel assignment

prevention purpose

(1) Subjects (irrespective of gender) must be healthy and >=12 years of age at screening.
(2) Subjects must freely provide documented informed consent. Children who are younger than 18 years of age must have the written consent of a legally acceptable representative and must personally consent using a consent form or assent form.
(3) Subjects must have received at least 2 doses of an authorized mRNA COVID-19 vaccine (COMIRNATY or SPIKEVAX) and satisfy the following criteria:
(a) Received 2 doses of an authorized mRNA COVID-19 vaccine (monovalent: Wuhan strain) as initial immunization
(b) At the time of screening, at least 3 months have passed since the last vaccination
(c) Receipt of these vaccines is supported by documentation, etc.

(1) Individuals with acute medical illness or fever of >= 37.5 degree celcius within 1 day prior to screening. These individuals may be offered the opportunity to enter the study after fever and illness have resolved.
(2) Individuals with a positive SARS-CoV-2 antigen test at screening or confirmed SARS-Cov-2 infection in a family member with whom they live.
(3) Individuals with a confirmed SARS-CoV-2 infection or history of COVID-19 with ongoing sequelae within 6 months.

Both

Prevention of SARS-CoV-2 infection

CSL402: Administer 0.5 mL (5 micro g) as a single intramuscular injection.

SARS-CoV-2, COVID-19

Geometric mean titer (GMT) of neutralizing antibodies against SARS-CoV-2 (Omicron JN.1) on Day 29

+81-3-5050-4268

Oct. 23, 2024

None