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A phase III, randomized, active-comparator, non-inferiority study to demonstrate the Immunogenicity and Safety of DS-5670a (COVID-19 vaccine) in children 12 through 17 years of age.

A phase III, randomized, active-comparator, non-inferiority study to demonstrate the Immunogenicity and Safety of DS-5670a in children 12 through 17 years of age.

131

In this study, a total of 131 participants were randomized, with 88 in the DS-5670a group and 43 in the Comirnaty intramuscular injection group. Out of the131 participants, 126 participants ((DS-5670a group, n=87, Comirnaty intramuscular injection group, n=39) were included in the Immunogenicity Evaluable PPS. The average (standard deviation [SD]) age of participants in the DS-5670a group was 13.2(1.39) years old, with 52 males (59.8%) and 35 females (40.2%). The average (standard deviation [SD]) age of participants in the Comirnaty intramuscular injection group was 13.8 (1.76) years old, with 15 males (38.5%) and 24 females (61.5%).

131 participants (88 in the DS-5670a group, 43 in the Comirnaty intramuscular injection group, and the following in the same order) were randomized. In the DS-5670a group, 98.9% (87/88) received the investigational vaccine for the first-time dose, and in the Comirnaty intramuscular injection group, 97.7% (42/43) received the investigational vaccine for the first dose and were included in the safety analysis set. Among the participants in the safety analysis set, 100.0% (87/87) in the DS-5670a group and 95.2% (40/42) in the Comirnaty intramuscular injection group received the investigational vaccine for the second dose. Among the randomized 131 participants, 129 participants (87 and 42) were included in the full analysis set (FAS), excluding 2 participants (1 and 1) who did not receive the investigational vaccine at all. Among the randomized 131 participants, 2 participants (1 and 1) who did not receive the investigational vaccine at all, 2 participants (0 and 2) who did not receive the investigational vaccine twice as specified in the protocol and 3 participants (1 and 2) with significant deviations from the protocol were excluded from the per-protocol set (PPS) (126 participants [87 and 39] were included. The reasons of exclusion were overlapped.). Among the FAS, 128 participants (87 and 41) were included in the Immunogenicity Evaluable FAS, excluding 1 participant (0 and 1) who had no immunogenicity data after the administration of the investigational vaccine. Among the randomized 131 participants, 2 participants (1 and 1) who did not receive the investigational vaccine at all, 2 participants (0 and 2) who did not receive the investigational vaccine twice as specified in the protocol, 1 participant (0 and 1) who had no immunogenicity data after the administration of the investigational vaccine and 3 participants (1 and 2) with significant deviations from the protocol were excluded from the Immunogenicity Evaluable PPS (126 participants [87 and 39] were included. The reasons of exclusion were overlapped.).

The incidence rates of solicited adverse events (injection site and systemic) were 97.7% (85/87) in the DS-5670a group and 100.0% (42/42) in the Comirnaty intramuscular injection group. The incidence rates of solicited injection site adverse events in participants were 97.7% (85/87) in the DS-5670a group and 97.6% (41/42) in the Comirnaty intramuscular injection group. The most frequently observed solicited injection site adverse events in both vaccinated groups were injection site pain and warmth after both the first and second doses. Warmth was more frequently observed after the second dose compared to the first dose in both vaccinated groups. The incidence rates of solicited systemic adverse events were 92.0% (80/87) in the DS-5670a group and 83.3%(35/42) in the Comirnaty intramuscular injection group. The most frequently observed solicited systemic adverse events in both vaccinated groups were fever, fatigue and headache after both the first and second doses. The incidence rates of each solicited systemic adverse event were higher after the second dose compared to the first dose. The incidence rates of severe solicited adverse events (injection site and systemic) were 28.7% (25/87) in the DS-5670a group and 16.7% (7/42) in the Comirnaty intramuscular injection group. The incidence rate of severe solicited injection site adverse events after the second dose was higher than the ones after the first dose in the DS-5670a group. The most frequently observed severe solicited injection site adverse event after the first dose was pain in both vaccinated groups. The most frequently observed severe solicited injection site adverse events after the second dose were swelling in the DS-5670a group and pain in the Comirnaty intramuscular injection group. Other solicited injection site adverse events were mild to moderate in severity. The incidence rate of severe solicited systemic adverse events after the second dose was higher than the ones after the first dose in the DS-5670a group. The most frequently observed severe solicited systemic adverse events after the first dose were fever and fatigue in the DS-5670a group and fever, fatigue and headache in the Comirnaty intramuscular injection group. The most frequently observed severe solicited systemic adverse event after the second dose was fever in both vaccinated groups. Other solicited systemic adverse events were mild to moderate in severity. The incidence rates of unsolicited adverse events were 40.2% (35/87) in the DS-5670a group and 28.6% (12/42) in the Comirnaty intramuscular injection group. The most frequently observed unsolicited adverse events in the DS-5670a group were nasopharyngitis, oropharyngeal pain, and injection site pruritus. The injection site pruritus was the adverse reaction. Severe unsolicited adverse events, deaths, serious adverse events and adverse events leading to discontinuation were not reported.

- The adjusted ratio of geometric mean titers (GMT) of the serum neutralizing activities against SARS-CoV-2 (original strain) 4 weeks after the second dose of the investigational vaccine (Day 57) (DS-5670a group/Comirnaty intramuscular injection group) was calculated as 1.103 (95% confidence interval: 0.777-1.564), with the adjusted difference in seroconversion rate (DS-5670a group - Comirnaty intramuscular injection group) of 0.0% (95% confidence interval: -4.9-10.4). - The adjusted ratio of geometric mean fold rise (GMFR) of serum neutralizing activities against SARS-CoV-2 (original strain) 4 weeks after the second dose of the investigational vaccine (Day 57) between the DS-5670a group and the Comirnaty intramuscular injection group (DS-5670a group/Comirnaty intramuscular injection group) was 1.103 (95% confidence interval: 0.777-1.564). - The ratio of COVID-19 incidence rates between the DS-5670a group and the Comirnaty intramuscular injection group during the trial period was 3.71 (95% confidence interval: 0.50-164.77).

In this study, the non-inferiority criteria set for geometric mean titer and seroresponse rate of serum neutralizing activities against SARS-CoV-2 (original strain) in this study were met, and the non-inferiority of DS-5670a to Comirnaty was confirmed. No new safety concerns were observed.

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https://jrct.niph.go.jp/latest-detail/jRCT2031220400

Inoguchi Akihiro

DAIICHI SANKYO Co.,Ltd.

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

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

DAIICHI SANKYO Co.,Ltd.

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

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Complete

Oct. 24, 2022

Interventional

randomized controlled trial

double blind

active control

parallel assignment

prevention purpose

1)Children aged 12 to 17 years at the time of informed consent.
2)Subjects who have legal representative signed a written informed consent
3)Subjects who have no history of vaccination against SARS-CoV-2 at the time of consent.
4)Subjects who are willing and able to comply with all scheduled requirements including medical examinations, laboratory tests, and report any symptoms. (possibly filed by legal representative )

1)Subjects who have a history of seizure or epilepsy due to vaccination.
2)Subjects who have a history of myocarditis or pericarditis
3))Subjects who have had a positive result of SARS-CoV-2 infection test or diagnosed as SARS-CoV-2 infection by medical attention within three months of consent
4)Subjects who have suggestive symptoms of SARS-CoV-2 infection (respiratory symptoms, headache, malaise, olfactory disturbance, taste disturbance, pharyngalgia etc.) at the time of consent.
5)Subjects who have a positive result of SARS-CoV-2 antigen test at the time of eligibility assessment.
6)Subjects who have a history of anaphylaxis or severe allergy to food, pharmaceuticals, cosmetics, vaccination, etc.

Both

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

A intramuscular injection of DS-5670a or Comirnaty twice in total

Geometric mean titer (GMT) and seroconversion rate of serum neutralizing activity against SARS-CoV-2 4 weeks after the second dose of the study drug (Day 57)

Efficacy
- Geometric mean fold rise (GMFR) of serum neutralizing activity against SARS-CoV-2 4 weeks after the second dose of the study drug (Day 57)
- The incidence of COVID-19 infection within 52 weeks from the administration of study drug (Day 393)

Safety
- Specified adverse events (injection site and systemic), Non-specified adverse events, Serious adverse events, Laboratory test values

+81-3-3517-6688

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