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A Phase 3, Randomized, Active-Comparator, Observer-Blind, Non-Inferiority Study of DS-5670a (COVID-19 Vaccine) in Adults Aged 18 Years and Older

A Phase 3, Randomized, Active-Comparator, Observer-Blind, Non-Inferiority Study of DS-5670a in Adults Aged 18 Years and Older

450

In this study, a total of 450 participants were randomized, with 226 in the DS-5670a group and 224 in the Comirnaty intramuscular injection group. Out of the DS-5670a group, 225 participants received the investigational vaccine, while in the Comirnaty intramuscular injection group, 220 participants received the investigational vaccine (5 participants withdrew before receiving the investigational vaccine). The average (standard deviation [SD] ) age of participants in the DS-5670a group was 45.3 (13.62) years old, with 154 males (68.4%) and 71 females (31.6%). The average (standard deviation [SD] ) age of participants in the Comirnaty group was 42.7 (14.99) years old, with 143 males (65.0%) and 77 females (35.0%).

450 participants (226 in the DS-5670a group, 224 in the Comirnaty intramuscular injection group, and the following in the same order) were randomized. In the DS-5670a group, 99.6% (225/226) received the investigational vaccine for the first timedose, and in the Comirnaty intramuscular injection group, 98.2% (220/224) received the investigational vaccine for the first dose and were included in the safety analysis set. Among the participants in the safety analysis set, 98.3% (221/225) in the DS-5670a group and 96.8% (213/220) in the Comirnaty intramuscular injection group received the investigational vaccine for the second dose. Among the randomized participants, 445 participants (225 in the DS-5670a group, 220 in the Comirnaty intramuscular injection group) were included in the full analysis set (FAS), excluding 5 participants (1 and 4) who did not receive the investigational vaccine at all. Among the FAS, 11 participants (4 and 7) who did not receive the investigational vaccine twice as specified in the protocol and 3 participants (3 and 0) with significant deviations from the protocol were excluded from the per-protocol set (PPS) (431 participants [218 and 213]). Among the randomized 450 participants (226 and 224), 438 participants (222 and 216) were included in the Immunogenicity Evaluable FAS, excluding 5 participants (1 and 4) who did not receive the investigational vaccine at all and 7 participants (3 and 4) who had no immunogenicity data after the administration of the investigational vaccine. Among the Immunogenicity Evaluable FAS, 11 participants (4 and 7) who did not receive the investigational vaccine twice as specified in the protocol and 3 participants (3 and 0) with significant deviations from the protocol (including overlapping exclusion reasons) were excluded from the Immunogenicity Evaluable PPS (431 participants [218 and 213]).

The incidence rates of solicited adverse events (injection site and systemic) were 94.2% (212/225) in the DS-5670a group and 94.1% (207/220) in the Comirnaty intramuscular injection group. The incidence rates of solicited injection site adverse events in participants who had solicited adverse events were 98.6% (209/212) in the DS-5670a group and 98.1% (203/207) 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. Redness, swelling, warmth, and pruritus were 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 76.9% (163/212) in the DS-5670a group and 58.5% (121/207) in the Comirnaty intramuscular injection group. The most frequently observed solicited systemic adverse events after the first dose were fatigue, headache, and myalgia, and after the second dose were fatigue, headache, myalgia, and fever. The incidence rates of solicited systemic adverse events were higher after the second dose compared to the first dose in both vaccinated group. The incidence rates of severe solicited adverse events (injection site and systemic) in participants who had solicited adverse events were 13.2% (28/212) in the DS-5670a group and 3.9% (8/207) in the Comirnaty intramuscular injection group. The severe solicited injection site adverse events after the first dose were swelling, induration, pain, and warmth in the DS-5670a group. The most frequently observed severe solicited injection site adverse events after the second dose were redness in the DS-5670a group and warmth in the Comirnaty intramuscular injection group. The most frequently observed severe solicited systemic adverse events after both the first and second doses were fever in both vaccinated groups. The incidence rates of severe solicited systemic adverse events after the first and second doses were similar in the Comirnaty intramuscular injection group, but higher after the second dose compared to the first dose in the DS-5670a group. Other solicited systemic adverse events were mild to moderate in severity. The incidence rates of unsolicited adverse events were 34.2% (77/225) in the DS-5670a group and 23.2% (51/220) in the Comirnaty intramuscular injection group. The most frequently observed unsolicited adverse events in the DS-5670a group were injection site erythema, injection site swelling, injection site induration, injection site pruritus, COVID-19 and fever. Except for COVID-19 and fever, the most frequent adverse reactions were similar to the adverse events in the DS-5670a group. Severe unsolicited adverse events included breast cancer, injection site erythema, injection site swelling, and hospitalization in the DS-5670a group, and pneumonia in the Comirnaty intramuscular injection group. The causality with the investigational vaccine was determined as "not related" for breast cancer and hospitalization in the DS-5670a group, as "not related" for pneumonia in the Comirnaty intramuscular injection group, but as "related" (adverse reaction) for injection site erythema and swelling in the DS-5670a group. No deaths were reported. Serious adverse events were observed in 9 (4.0%) participants in the DS-5670a group and 4 (1.8%) participants in the Comirnaty intramuscular injection group. In the DS-5670a group, these events included hospitalisation in 2 participants, breast cancer, cerebral infarction, epiretinal membrane, acute myocardial infarction/cardiac aneurysm/cardiac failure/cardiac ventricular thrombosis, rotator cuff syndrome, glycosylated haemoglobin increaced, and liver function test increased in 1 participant each. In the Comirnaty intramuscular group, these events included pneumonia, bladder cancer, vertigo positional, and pneumothorax in 1 participant each. None of these events were determined to be related to the investigational vaccine. One serious adverse event leading to discontinuation was observed only in one subject (breast cancer) in the DS-5670a group.

The 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) based on the analysis of covariance (ANCOVA) model (DS-5670a group/Comirnaty intramuscular injection group) was calculated as 0.746 (95% confidence interval: 0.586-0.958), with a difference in seroconversion rate (DS-5670a group - Comirnaty intramuscular injection group) of -4.7% (95% confidence interval: -10.5% to 1.0%). The 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 0.755 (95% confidence interval: 0.594-0.959). The seroconversion rates 4 weeks after the second dose of the investigational vaccine (Day 57) were 89.4% in the DS-5670a group and 94.1% in the Comirnaty intramuscular injection group. The ratio of COVID-19 incidence rates (95% confidence interval) between the DS-5670a group and the Comirnaty intramuscular injection group during the trial period was 1.60 (0.62-4.46).

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 not met, and the non-inferiority of DS-5670a to Comirnaty was not confirmed. No new safety concerns were observed.

No

https://jrct.niph.go.jp/latest-detail/jRCT2031220264

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

Sept. 01, 2022

Interventional

randomized controlled trial

double blind

active control

parallel assignment

prevention purpose

1)Healthy adults >= 18 years of age at the time of consent
2)Has signed and dated a written informed consent form (ICF).
3)With no history of vaccination against SARS-CoV-2.
4)Willing and able to comply with all scheduled requirements (including medical examinations, laboratory tests), and report any symptoms.

1)Known medical history of convulsion or seizure epilepsy due to vaccination.
2)Known medical history of myocarditis or underlying condition of myocarditis.
3)Has been diagnosed with SARS-CoV-2 infection by (RT-PCR test, SARS-CoV-2 antigen test, or SARS-CoV-2 antibody test in the past.
4)Has suggestive symptoms of SARS-CoV-2 infection (respiratory symptoms, headache, malaise, olfactory disturbance, taste disturbance, pharyngalgia etc.) at the time of consent.
5)Has a positive result on the screening for SARS-CoV-2 infection (antigen test or antibody test) at the confirmation of eligibility.
6)Known medical history of immediate systemic allergic reactions such as anaphylaxis, angioedema, or severe allergy to food, pharmaceuticals, cosmetics, vaccines, 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 SARS-CoV-2 infection within 52 weeks from the administration of study drug (Day 393)
Safety:
- Solicited adverse events (injection site and systemic)
- Unsolicited adverse events
- Serious adverse events
- Laboratory test results

+81-3-3263-4801

Aug. 19, 2022

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