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Open-label, uncontrolled, phase I / II study of the safety and immunogenicity of intracutaneous inoculation of the COVID-19 DNA vaccine (AG0302-COVID19) in healthy adults

Phase I / II study of intracutaneous inoculation of COVID-19 DNA vaccine (AG0302-COVID19)

20

Twenty patients (10 in the ID low-dose group and 10 in the ID high-dose group, in the same order) were enrolled in this study: 4 males and 6 females in the ID low-dose group and 5 males and 5 females in the ID high-dose group. The mean (standard deviation) age was 46.8 (10.6) years in the low-dose ID group and 44.2 (15.3) years in the high-dose ID group. 60.0% (6/10) of the patients in the low-dose ID group and 50.0% (5/10) in the high-dose ID group were under 50 years old.

Twenty subjects (10 in the low ID dose group and 10 in the high ID dose group, in that order) were enrolled in the study. All subjects received the prescribed number of doses and completed the vaccination and observation periods. Of these, 6 subjects (2 and 4) completed the follow-up period, 13 subjects (8 and 5) withdrew consent, and 1 subject (in the ID high-dose group) discontinued the study during the follow-up period for his/her own reasons. In the 13 cases of discontinuation due to withdrawal of consent, the study was discontinued because the subjects wished to be publicly vaccinated after receiving notification from the Pharmaceuticals and Medical Devices Agency and distributing a letter urging participation in a public vaccination program for approved vaccines.

There were no adverse events that resulted in death during the study period. From the time of the first dose of study drug to 8 weeks after the first dose (inoculation and observation periods), no serious adverse events occurred. From 8 weeks after the first dose of study drug to 52 weeks after the first dose (follow-up period), one patient in the high ID dose group reported a serious adverse event (disc protrusion), but the outcome recovered and was not causally related to study drug. There were no adverse events that led to discontinuation of study drug inoculation.

No notable safety issues were observed with the two intradermal inoculations of AG0302-COVID19, and there were no notable differences compared to the safety of the intramuscular inoculation (AG0302-COVID19-JN-01 study). Regarding immunogenicity, SARS-CoV-2 spike (S) glycoprotein-specific antibody titers prior to the first dose of study drug were below the cut point in all subjects in the low ID dose group and above the cut point in three subjects in the high ID dose group. Antibody titers at 2, 4, 6, and 8 weeks after the first dose of study drug were above the cut point in 2 subjects in the ID low-dose group (2 time points total) and in 3 subjects in the ID high-dose group (12 time points total).

No notable safety issues were observed with the two intradermal inoculations of AG0302-COVID19, and there were no notable differences compared to the safety of the intramuscular inoculation (AG0302-COVID19-JN-01 study). Regarding immunogenicity, an immune response was observed in some subjects after AG0302-COVID19 intradermal inoculation, but no significant antibody production was observed.

Aug. 30, 2022

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9503587/

No

https://jrct.niph.go.jp/latest-detail/jRCT2051200085

RAKUGI Hiromi

Osaka University Hospital

2-15 Yamadaoka, Suita, Osaka 565-0871

rakugi@geriat.med.osaka-u.ac.jp

ASANO Kento

Osaka University Hospital

4F, Center of Medical Innovation and Translational Research, 2-2 Yamadaoka, Suita, Osaka 565-0871

+81-6-6210-8290

k-asano@dmi.med.osaka-u.ac.jp

Complete

Nov. 25, 2020

Interventional

non-randomized controlled trial

open(masking not used)

dose comparison control

parallel assignment

prevention purpose

(1) Subjects who have obtained written consent voluntarily to participate in this clinical trial
(2) Subjects whose age at the time of obtaining consent is 20 years to 75 years
(3) Subjects who are negative for SARS-CoV-2 by PCR test
(4) Subjects who are negative for both SARS-CoV-2 IgM antibody and SARS-CoV-2 IgG antibody by antibody test

(1) Subjects with symptoms of suspected COVID-19 infection (respiratory symptoms, headache, malaise, olfactory disorders, taste disorders, etc.)
(2) Subjects with a history of COVID-19 (hearing from subjects)
(3) History of participation (history of inoculation) for the unapproved vaccine clinical trials
(4) Subjects with axillary temperature of 37.0 degree or higher
(5) Subjects who have a history of anaphylaxis due to the food or the drugs etc.
(6) Medical history of serious cardiovascular system, haemal system, respiratory system, liver, kidney, digestive system and neuropsychiatric system, or subjects who has a current medical history
(7) Subjects with a history of convulsion or epilepsy
(8) Subjects with a history of diagnosis of immunodeficiency
(9) Subjects who have a close relative (within 3rd degree) of congenital immunodeficiency
(10) Subjects who have a history of bronchial asthma
(11) Subjects who had a fever of 39.0 degree or higher within 2 days after the last vaccination, and those who suspected allergy such as a systemic rash
(12) Females who wish to become pregnant from the date of study registration to 12 weeks after the first inoculation of the investigational drug, and pregnant females who are breast-feeding. In addition, females who may become pregnant and their male sexual partners should use appropriate contraceptives (pill), condoms, vasectomy, tubal ligation, diaphragm, intrauterine devices, spermicides, intrauterine hormone-releasing system, etc. from the study entry date until 12 weeks after vaccination
(13) Subjects who have participated in clinical trials of other unapproved drugs and received the investigational drug within 4 weeks before the start of this clinical trial (starting from vaccination day)
(14) Subjects who have been received a live vaccine, inactivated vaccine, or toxoid within 4 weeks before the start of this clinical trial (starting from vaccination day)
(15) Subjects who have been administered with drugs that affect the immune system (however, excluding external preparations) such as immunomodulators (DMARDs, etc.), immunosuppressants, biologics, etc. within 4 weeks from vaccination
(16) Subjects who received blood transfusion or gamma globulin therapy within 12 weeks before vaccination, or high-dose gamma globulin therapy (200 mg/kg or more) within 24 weeks before vaccination
(17) Subjects who have a history of overseas travel within 4 weeks before the start of the clinical trial (starting from vaccination day)
(18) Subjects who are unable to comply with the clinical trial protocol and follow up (for mental, family, social or geographical reasons)
(19) Subjects who are judged to be ineligible for this clinical trial by the investigator

Both

COVID-19

Inoculate AG0302-COVID19 intracutaneously

1. Safety
Information such as the type, frequency and severity of adverse events that occurred from the time of the first inoculation of the investigational drug to 8 weeks after the first inoculation will be collected to evaluate the safety.
2. Immunogenicity
Rate of change from baseline in SARS-CoV-2 spike (S) glycoprotein-specific antibody titers 2 weeks after the first inoculation of the investigational drug (immediately before the second inoculation), 4 weeks, 6 weeks, and 8 weeks Analyze and assess immunogenicity.

+81-6-6210-8290

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