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A Phase 1 study to assess the safety, tolerability, and immunogenicity of VN-0200 after intramuscular injection in Japanese healthy adults and elderly subjects

A Phase 1 study to assess the safety, tolerability, and immunogenicity of VN-0200 after intramuscular injection in Japanese healthy adults and elderly subjects

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In Step 1 (healthy adults), the mean (SD) age was 37.0 (8.75) years, the mean (SD) body weight was 59.42 (7.935) kg, and the proportion of males was 50.0% (12/24 subjects), with no apparent difference among the treatment groups. In Step 2 (healthy elderly subjects), the mean (SD) age was 70.0 (3.94) years, the mean (SD) body weight was 58.88 (9.409) kg, and the proportion of male was 54.2% (13/24 subjects). In the safety analysis set, the proportion of males was higher than that of female and the mean body weight was greater in the placebo group than in the other VN-0200 groups; however, there was no apparent difference in the mean age or BMI among the treatment groups. The demographic data for the immunogenicity analysis set in both healthy adults and healthy elderly subjects were identical with those for the safety analysis set.

In healthy adults, 24 subjects (placebo group: 6 subjects, VN-0200 groups: 18 subjects [3 dose (cohort1: VAGA-9001a (antigen) 100ug + MABH-9002b (adjuvant) 100ug, cohort2 : antigen 200ug + adjuvant 200ug, cohort3 : antigen 400ug + adjuvant 400ug), each 6 subjects], the same order as below) were randomized. 23 subjects (6 and 17 subjects) completed the study, and 1 subject (0 and 1 subject) discontinued the study due to an adverse event (COVID-19) after the second injection of the study drug. In healthy elderly subjects, 24 subjects (6 subjects, 18 subjects [3 dose (cohort1 : antigen 100ug + adjuvant 100ug, cohort2 : antigen 200ug + adjuvant 200ug, cohort3 : antigen 400ug + adjuvant 400ug), each 6 subjects]) were randomized. Twenty-four subjects received the first injection of the study drug, and 23 subjects (6 subjects and 17 subjects) received the second injection of the study drug and completed the study. One subject (1 subject, 0 subjects) discontinued the study due to withdrawal of consent after the first injection of the study drug.

In healthy adults, the incidence of adverse events was 16.7% (1/6 subjects) in the placebo group and 94.4% (17/18 subjects) in the overall VN-0200 groups. The incidence of the solicited adverse events (injection site pain, injection site redness, injection site induration, injection site swelling, injection site pruritus, injection site warmth) was 0.0% (0/6 subjects) in the placebo group and 77.8% (14/18 subjects) (cohort1: 66.7% [4 subjects], cohort2: 66.7% [4 subject], cohort3: 100.0% [6 subjects]) in the overall VN-0200 groups, the incidence of the solicited systemic adverse events (pyrexia, headache, malaise, myalgia, rash) was 0.0% in the placebo (0/6 subjects), 33.3 % (6/18 subjects) (cohort1: 33.3% [2 subjects], cohort2: 33.3% [2 subjects], cohort3 :33.3% [2 subjects]) in the overall VN-0200 groups. Common solicited adverse events were injection site pain, malaise, injection site warmth, injection site erythema, fever, and headache. The incidence of adverse events was higher in all the VN-0200 groups than in the placebo group. All the adverse events were mild or moderate in severity, and no severe adverse events were reported in this study. In healthy elderly subjects, the incidence of adverse events was 33.3% (2/6 subjects) in the placebo group and 66.7% (12/18 subjects) in the overall VN-0200 groups. The incidence of the solicited adverse events was 16.7% (1/6 subjects) in the placebo group and 61.1% (11/18 subjects) (cohort1: 50.0% [3 subjects], cohort2: 66.7% [4 subjects], cohort3: 66.7% [4 subjects]) in the overall VN-0200 groups, the incidence of the solicited systemic adverse events was 0.0% in the placebo (0/6 subjects), 22.2 % (4/18 subjects) (cohort1: 16.7% [1 subject], cohort2: 33.3% [2 subjects], cohort3: 16.7% [1 subject]) in the overall VN-0200 groups. Common solicited adverse events were injection site pain, injection site erythema, injection site induration, injection site swelling, and injection site warmth. The incidence of adverse events was higher in all the VN-0200 groups than in the placebo group. All the adverse events were mild or moderate in severity, and no severe adverse events were reported in this study. No deaths, serious adverse events, or potential immune-mediated disease (pIMD) were reported in this study. Moderate COVID-19 (healthy adults, VN-0200 group) was reported as an adverse event leading to discontinuation in 1 subject. It was assessed as unrelated to the study treatment.

< Safety > Refer to "Adverse events" section. <Immunogenicity> -Anti-respiratory syncytial virus subgroup A(RSV/A) neutralizing activity in blood In healthy adults, the geometric mean titer (GMT) for anti-RSV/A neutralizing activity in blood showed no apparent change from baseline in the placebo group and increased in the VN-0200 groups. No apparent difference was observed in the geometric mean fold rise (GMFR) between Day 29 and Day 57 in all the VN-0200 groups. No apparent difference was observed in the increase in GMT of blood anti-RSV/A neutralizing activity among the VN-0200 groups (cohort1: Day 29 3.48-fold, Day 57 3.66-fold, cohort2: Day 29 2.15-fold, Day 57 1.77-fold, cohort3: Day 29 2.76-fold, Day 57 2.40-fold). In healthy elderly subjects, the GMT for anti-RSV/A neutralizing activity in blood showed no apparent change from baseline in the placebo group and increased in the VN-0200 groups. The lower limit of 95% CI of GMFR was above 1.0 on Day 29 and Day 57 in all the VN-0200 groups. No apparent difference in GMFR was observed between Day 29 and Day 57 in any of the treatment groups. No apparent difference was observed in the increase in GMT of anti-RSV/A neutralizing activity in blood among the VN-0200 groups (cohort1: Day 29 4.05-fold, Day 57 4.49-fold, cohort2: Day 29 2.79-fold, Day 57 2.78-fold, cohort3: Day 29 3.15-fold, Day 57 3.06-fold). -VAGA-9001a (antigen)-specific interferon (IFN)-gamma production response Both in healthy adults and healthy elderly subjects, the number of VAGA-9001a-specific IFN-gamma-producing T cells was increased on Day 57 compared with that before the first injection and it was higher in all VN-0200 groups than in the placebo group. It is noted that the interpretation of the results is limited due to the large number of missing data.

Intramuscular injection of VN-0200 was well tolerated with no safety concerns in either healthy adults or healthy elderly subjects. Intramuscular injection of VN-0200 induced neutralizing activity against RSV/A in healthy adults and healthy elderly subjects.

No

https://jrct.niph.go.jp/latest-detail/jRCT2031210069

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

May. 20, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

prevention purpose

1. Japanese healthy subjects.
2. Age >=20 and <=50 years upon providing informed consent at step1 or Age >=65 and <=80 years upon providing informed consent at step2.
3. Body mass index (BMI) >=18.0 and <30.0 kg/m2 at screening.

1. Subjects with a history of anaphylaxis or severe allergies due to food, medicine, insect bites, cosmetics, or vaccination
2. Having alcohol or drug dependence etc.

Both

Prevention of respiratory syncytial virus

VN-0200 (antigen: VAGA-9001a, adjuvant: MABH-9002b) or placebo 0.5 mL is administered twice on Day 1 and Day 29.

Safety:Adverse events, specific adverse events, Potential Immune-Mediated Disease, laboratory data, body weight, vital signs and 12-lead ECGs,

Geometric Mean Fold Rise (GMFR) of Anti-RSV Specific Neutralizing activity, Geometric Mean Titer (GMT) of anti-VAGA-9001a IgG, GMT of anti-RSV G IgG, VAGA-9001a-specific IFN-gamma production

+81-3-5366-3006

May. 11, 2021

none