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A Ph2, randomized, double-blind, dose finding study to describe the immunogenicity, safety and tolerability of VN-0200 in Japanese adults aged 60-80 years

A Ph2, randomized, double-blind, dose finding study to describe the immunogenicity, safety and tolerability of VN-0200 in Japanese adults aged 60-80 years

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In the immunogenicity analysis set, the mean (standard deviation [SD]) age was 66.2 (5.18) years. The percentage of male subjects was 56.5%. The mean (SD) body weight was 62.55 (11.586) kg. Although there was a slight difference in the sex percentage (female: 30.0% to 63.2%), no significant differences were found in the background of the enrolled subjects among the treatment groups. The demographic and other baseline characteristics of the safety analysis set were similar to those of the immunogenicity analysis set.

A total of 342 subjects were randomized in the study. One subject was not treated, and 341 subjects were included in the safety analysis set. The immunogenicity analysis set included 338 subjects.(hereafter, treatment groups indicated as VAGA-9001a Dose [ug]/MABH-9002b Dose [ug], 18 subjects in the 100/0 group, 40 subjects in the 100/100 group, 40 subjects in the 100/200 group, 40 subjects in the 100/400 group, 21 subjects, in the 200/0 group, 40 subjects in the 200/400 group, 19 subjects in the 400/0 group, 40 subjects in the 400/100 group, 39 subjects in the 400/200 group, 41 subjects in the 400/400 group). A total of 3 subjects were excluded from the immunogenicity analysis set for the following reasons: no available immunogenicity data in 3 subjects (2 subjects in 100/0 group and 1 subject in the 400/200 group). Overall, 97.7% (333/341) of the subjects completed both administrations. Eight subjects discontinued the study after the first administration due to reasons such as withdrawal.

No fatal TEAEs were reported in the observation period. Serious TEAEs were reported in 4 subjects (1.2%) (2 subjects in the 100/0 group and 1 subject each in the 100/100 and 100/400 groups). No study drug-related serious TEAEs were reported. The TEAEs led to discontinuation of study treatment, or study discontinuation were reported in 4 subjects (1.2%) (1 subject each in the 100/0 and 400/200 groups, and 2 subjects in the 200/400 group). A study drug-related TEAE led to discontinuation was reported in 1 subject (limb discomfort) in the 200/400 group. The incidence of solicited AEs through the first and second administrations was higher in the 400/400, 400/100, and 400/200 groups than in the other treatment groups. The incidence of solicited AEs was 78.0% (32/41 subjects) in the 400/400 group, 72.5% (29/40 subjects) in the 400/100 group, and 67.5% (27/40 subjects) in the 400/200 group. Severe solicited AEs were reported in 2 subjects (5.0%, injection site redness and fever) in the 400/200 group, and 1 subject each in the 100/400 (2.5%, injection site redness), 200/400 (2.5%, fever), 400/100 (2.5%, injection site redness), and 400/400 (2.4%, injection site swelling) groups. No severe solicited AEs were reported in the other treatment groups. The most common solicited injection site AEs were injection site tenderness and injection site pain. Most solicited injection site AEs were mild or moderate. The incidence of solicited injection site AEs was higher after the second administration than after the first administration. The most common solicited systemic AEs were myalgia, malaise, and headache. Most solicited systemic AEs were mild or moderate. There were no notable differences in the incidence of solicited systemic AEs between after the first and second administrations. No notable differences were found in the incidence of unsolicited TEAEs between the treatment groups. The incidence of unsolicited TEAEs was 22.3% (76/341 subjects) in total. Severe unsolicited TEAEs were reported in 2 subjects (10.0%, Bilateral iliopsoas abscesses after MRSA bacteremia and right shoulder fracture) in the 100/0 group. No severe unsolicited TEAEs were reported in the other treatment groups. The study drug-related unsolicited TEAEs were reported in 16 subjects (4.7%) in total.

Primary Efficacy Endpoint: -The GMTs of anti-RSV/A neutralization activity in blood on Day 57 (28 days after the second administration) increased from baseline in all treatment groups. Since the GMFRs in the treatment groups with the adjuvant were similar to those in the treatment groups without the adjuvant, no clear adjuvant effect was found. No clear dose-response relationships of the antigen or adjuvant were also found. Secondary Efficacy Endpoints: -The GMTs of anti-RSV/A neutralization activity in blood on Day 29, and the GMTs of anti-RSV/B neutralization activities in blood and anti-VAGA-9001a antibody in blood on Day 29 and Day 57 increased from baseline in all treatment groups, but no clear dose-response relationship was observed for the antigen or adjuvant. Since the GMFRs in the treatment groups with the adjuvant were similar to those in the treatment groups without the adjuvant, no clear adjuvant effect was found. -The mean VAGA-9001a-specific IFN-gamma responses on Day 57 increased from baseline in all treatment groups. The VAGA-9001a-specific IFN-gamma responses were higher on Day 57 than those on Day 29. No clear dose-response relationship of the antigen or adjuvant was found.

The anti-RSV/A neutralization activity increased from baseline on 28 days after the first and second administration of VN-0200 in all treatment groups, but no clear dose-response relationship of the antigen or adjuvant was found within the dose range used in this study. VN-0200 was well tolerated with no safety concerns in all treatment groups.

Yes

De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/ Supporting Information: - Study Protocol - Statistical Analysis Plan (SAP) - Informed Consent Form (ICF) Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication. Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent. URL: https://vivli.org/ourmember/daiichi-sankyo/

https://jrct.niph.go.jp/latest-detail/jRCT2071220051

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. 12, 2022

Interventional

randomized controlled trial

double blind

dose comparison control

parallel assignment

prevention purpose

1) Healthy Japanese subjects aged 60 to 80 years of age at the time of informed consent.
2) Subjects who complied with the compliance instructions in the study, underwent physical examination and examinations specified in the protocol, and were able to report symptoms, etc.

-Serious cardiovascular, respiratory, hepatic, renal, gastrointestinal, or neuropsychiatric disorders.
-Serious acute illness.
-Has been diagnosed with congenital or acquired immunodeficiency.
-Previous vaccination with an RSV vaccine (including the investigational drugs)
-Having a history of anaphylaxis or severe allergies due to medicines, or vaccination, etc.
-Administration of gamma globulins, systemic immunosuppressants (including drugs for the treatment of autoimmune diseases), hematopoietics (excluding iron and vitamins), and corticosteroids (excluding topical preparations, inhalants, and small-dose short-term oral administration*) or planned administration of them in the period starting 28 days prior to informed consent and ending 28 days after the second vaccination. * <14 days, <=20 mg/day on a prednisolone basis.
-Planned or actual administration of other vaccine in the period starting 14 days prior to informed consent and ending 14 days after the second vaccination., etc.

Both

Prevention of respiratory syncytial viral infection

VN-0200 0.5 mL is intramuscularly administered twice at upper arm on Day 1 and Day 29.

Geometric mean titer (GMT) and geometric mean fold rise (GMFR) of anti-RSV/A (RSV subgroup A) neutralizing activity on 28 days after the second administration of the study drug (Day 57)

Efficacy
- GMT and GMFR of anti-RSV/A neutralizing activity on 28 days after the first administration of the Study Drug (Day 29)
- GMT and GMFR of anti-RSV/B (RSV subgroup B) neutralizing activity on Day 29 and Day 57
- GMT and GMFR of anti-VAGA-9001a antibody on Day 29 and Day 57
- Summary statistics of VAGA-9001a-specific IFN-r production responses on Day 29 and Day 57

Safety
- Solicited adverse events (injection site and systemic), Non-solicited adverse events, Serious adverse events, Laboratory test values, Potential immune-mediated disease (pIMD)

+81-92-283-7701

Aug. 26, 2022

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