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A Phase 1/2 study to assess the safety, immunogenicity and recommended dose of DS-5670a (COVID-19 Vaccine) in Japanese healthy adults and elderly subjects

A Phase 1/2 study to assess the safety, immunogenicity and recommended dose of DS-5670a in Japanese healthy adults and elderly subjects

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In the baseline characteristics for all healthy adults, the mean age (standard deviation [SD]) at informed consent was 42.3 (12.27) years. Thirty-one (38.8%) male and 49 (61.3%) female subjects were randomized. The mean BMI (SD) was 22.09 (2.863) kg/m^2. Subjects in the 60 ug group were younger than those in other groups. In the 10 ug, 30 ug, and 100 ug groups, more females were included than males, and in the placebo group, more males were included than females. Other demographic data were similar among groups. In the baseline characteristics for all healthy elderly subjects, the mean age (SD) at informed consent was 69.0 (2.75) years. Thirty-four (54.8%) male and 28 (45.2%) female subjects were randomized. The mean BMI (SD) was 23.39 (2.860) kg/m^2. In the 100 ug group, more females were included than males, and in the placebo and 30 ug groups, more males were included than females. Other demographic data were similar among the groups. The demographic data for the immunogenicity analysis set and the PK analysis set were identical with those for the safety analysis set, respectively.

80 healthy adults (16 healthy adults for each group) were randomized. 79 healthy adults (98.8%) completed observation period up to Day 57. One healthy adult discontinued the study due to an adverse event. Sixty-two healthy elderly subjects (14 subjects for DS-5670a 10 ug, 14 subjects for 30 ug, 10 subjects for 60 ug, 9 subjects for 100 ug, and 15 subjects for placebo) were randomized. Sixty-one healthy elderly subjects (98.4%) completed observation period up to Day 57. One healthy elderly subject discontinued the study due to "withdrawal by subject". Of 110 subjects (63 healthy adults, 47 healthy elderly subjects) who received either dose of DS-5670a and completed observation period up to Day 57, 89 subjects (51 healthy adults, 38 healthy elderly subjects) were withdrawn from the study in the 1-year follow-up period, and 21 subjects (12 healthy adults, 9 healthy elderly subjects) completed the follow-up period.

The incidence of adverse events in the DS-5670a Total group and placebo group was 96.9% (62/64) and 62.5% (10/16) in healthy adults and 91.5% (43/47) and 26.7% (4/15) in healthy elderly subjects, respectively. Commonly reported adverse events in the DS-5670a Total group in healthy adults and healthy elderly subjects were injection site pain (84.4% in healthy adults and 74.5% in healthy elderly subjects) and myalgia (54.7% in healthy adults and 74.5% in healthy elderly subjects), respectively. These adverse events were almost related to the study treatment. Of the solicited injection site adverse events reported in the DS-5670a treatment groups, the most frequently reported event was injection site pain (84.4% in healthy adults and 74.5% in healthy elderly subjects). Among the solicited systemic adverse events reported in the DS-5670a treatment groups, the most frequently reported events were myalgia (54.7% in healthy adults and 74.5% in healthy elderly subjects). Two serious adverse events (cervical vertebral fracture and concussion) were reported in 1 healthy adult in the 100 ug group and the subject discontinued the study due to the serious adverse events. These serious adverse events were due to a traffic accident and were assessed as unrelated to the study treatment. No safety concern was noted in the 1-year follow-up period. In this study, no serious adverse events related to the study drug were reported. the DS-5670a treatment is considered safe and well tolerable at doses of up to 100 ug in both healthy adults and healthy elderly subjects.

- Safety Refer to "Adverse events" section. - Immunogenicity The serum neutralization GMT against SARS-CoV-2 did not increase after the first administration of DS-5670a, but increased after the second administration. The SARS-CoV-2 neutralizing activity GMTs were higher in healthy adults than healthy elderly subjects and they peaked at Day 43 (14 days after the second administration) in any groups. In healthy adults, the serum SARS-CoV-2 neutralizing activity geometric mean titers (GMTs) in 30 ug or higher dose groups were higher than those in the 10 ug group. The seroconversion rates (defined as proportion of subjects with >=4-fold rise) in the neutralization titers on Day 43 and 57 increased with increasing doses over the dose range evaluated (10 ug to 100 ug). In healthy elderly subjects, the neutralizing activity GMTs and the seroconversion rates were increased with increasing doses over the dose range evaluated (10 ug to 100 ug). The seroconversion rate of 100% was observed in 100 ug dose group in both healthy adults and healthy elderly subjects. The SARS-CoV-2 neutralization titers and receptor binding domain (RBD)-binding IgG antibody concentrations were positively correlated in healthy adults and healthy elderly subjects. The SARS-CoV-2 neutralizing activity decreased from the peak at Day 43 and Day 57 to almost baseline levels in the follow-up period up to Day 394 (1 year after second administration) in any dose group for both healthy adults and elderly subjects. - Pharmacokinetics In healthy adults, the median Tmax of MAFB-7566a was approximately 2-4 hours in each treatment group after the first administration and approximately 2-14 hours after the second administration. The mean Cmax after the first administration of MAFB-7566a increased with dose in the range from 10 to 100 ug of DS-5670a. No apparent correlation was observed between the mean AUClast of MAFB-7566a and the dose of DS-5670a. The mean Cmax and AUClast after the second administration were lower than those after the first administration except in the 60 ug group. In healthy elderly subjects, the median Tmax of MAFB-7566a was approximately 1-2 hours in each treatment group after the first and second administration. The mean Cmax of MAFB-7566a increased with dose in the range from 10 ug to 100 ug in the first administration and from 10 ug to 60 ug in the second administration. No apparent correlation was observed between the mean AUClast of MAFB-7566a and the dose of DS-5670a. The mean Cmax and AUClast after the second administration were lower than those after the first administration except for AUClast in the 60 ug group. After both the first and second administrations, the plasma concentrations of cationic lipid were below the LLOQ in all measurement samples in the 10 ug and 30 ug groups of healthy adults and healthy elderly subjects.The plasma concentrations of cationic lipid in almost all the measurement samples were below the LLOQ in the 60 ug group. In the 100 ug group, the median Tmax after the first administration was approximately 24 hours in healthy adults and 4 hours in healthy elderly subjects. The mean Cmax and AUClast of cationic lipids in plasma were highly variable, and no apparent difference was observed between healthy adults and healthy elderly subjects. The plasma PEG concentrations were below the LLOQ in almost all measurement samples.

The basic data on safety and immunogenicity for determining recommended dose were obtained in this phase 1/2 study. The recommended dose of DS-5670a will be decided according to the results of the future phase 2 study in addition to the information obtained from this study, considering that the formulation of DS-5670a was optimized after this phase 1/2 study.

No

https://jrct.niph.go.jp/latest-detail/jRCT2071200110

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

Mar. 12, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

prevention purpose

1) Japanese
2) Healthy adults aged >=20 and <65 years, or healthy elderly aged >=65 and <75 years (at the time of informed consent)
3) Body Mass Index (BMI) is >=17.5 and <30.0 kg/m^2 (at screening )
4) Subjects who can follow the compliance requirements during clinical trials, undergo medical examinations and tests specified by the protocol, and report symptoms, etc.

1) Having a history of anaphylaxis or severe allergies due to food, cosmetics, medicines, or vaccination.
2) Having alcohol or drug dependence.
3) Having a history of immunodeficiency or having a close relative with congenital immunodeficiency.
4) Having a history of SARS-CoV-2 infection.
5) Having fever of >=39.0 C or symptoms of suspected allergies such as systemic rash within 2 days after past vaccination.
etc.

Both

Prevention of COVID-19

A intramuscular injection of DS-5670a (10, 30, 60 or 100 ug) or placebo twice in total.

- Safety: Adverse events, specific adverse events, laboratory data, weight, vital signs and 12-lead ECGs
- Immunogenicity: Neutralizing antibodies against SARS-CoV-2 levels in blood

- Immunogenicity: Anti-IgG levels in blood
- Pharmacokinetics: Plasma concentration of MAFB-7566a and constituent lipids of LNP

+81-92-283-7701

Mar. 11, 2021

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