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A randomized, double-blind, confirmatory study of VN-100 in healthy elderly volunteers

VN-100 Ph3 non-inferiority study

901

To demonstrate the immunological non-inferiority of VN-100 versus subcutaneously administered influenza HA vaccine in healthy elderly volunteers 65 years and older

901 subjects (VN-100 group: 451 subjects, control group: 450 subjects) were randomized. The administered vaccine was 900 subjects (VN-100 group: 450 subjects, control group: 450 subjects) except for one subjects (VN-100 group) who stopped this study. All of the vaccinated subjects were completed in this study.

- Incidence of injection site AEs was 93.1% (419/450) in VN-100 group and 49.6% (223/450) in the control group. - Main injection site AEs were injection site erythema (VN-100 group: 90.4% (407/450), control group: 40.2% (181/450)), injection site swelling (VN-100 group: 50.2% (226/450), control group: 20.7% (93/450)), injection site pruritus (VN-100 group: 37.8% (170/450), control group: 17.6% (79/450)), injection site induration (VN-100 group: 28.2% (127/450), control group: 13.3% (60/450)), injection site hot feeling (VN-100 group: 26.9% (121/450), control group: 17.1% (77/450)), and injection site pain (VN-100 group: 16.2% (73/450), control group: 16.9% (76/450)). - The incidence of systemic AEs was 17.6% (79/150) and 14.9% (67/450) in the control group. - Main systemic AEs were fatigue (VN-100 group: 8.9% (40/450), control group: 8.9% (40/450)), headache (VN-100 group: 5.1% (23/450), control group: 8.2% (37/450)), and chills (VN-100 group: 2.7% (12/450), control group: 2.9% (13/450)).

The Healthy Japanese elderly 65 years and older were randomized at an equal ratio to either the VN-100 group or the licensed standard SC vaccine group, and following immunogenicity conclusion were obtained. - The seroconversion rate of the HI antibody titer on Day 21 was 72.22% (325/450) in VN-100 group and 61.56% (277/450) in the control group in the H1N1 strain. Difference in seroconversion rate between VN-100 group to control group was 10.67% (95% CI: 4.524%-16.70%). The GMT ratio of the HI antibody titer on Day 21 was 224.54 in VN-100 group and 155.39 in the control group in the H1N1 strain. Difference in GMT ratio between VN-100 group to control group was 1.45 (95% CI: 1.22-1.71). - The seroconversion rate of the HI antibody titer on Day 21 was 68.44% (308/450) in VN-100 group and 59.11% (266/450) in the control group in the H3N2 strain. Difference in seroconversion rate between VN-100 group to control group was 9.33% (95% CI: 3.05%-15.51%). The GMT ratio of the HI antibody titer on Day 21 was 437.13 in VN-100 group and 286.41 in the control group in the H3N2 strain. Difference in GMT ratio between VN-100 group to control group was 1.53 (95% CI: 1.28-1.82). - The seroconversion rate of the HI antibody titer on Day 21 was 55.11% (248/450) in VN-100 group and 46.67% (210/450) in the control group in the B strain. Difference in seroconversion rate between VN-100 group to control group was 8.44% (95% CI: 1.91%-14.88%). The GMT ratio of the HI antibody titer on Day 21 was 35.27 in VN-100 group and 27.00 in the control group in the B strain. Difference in GMT ratio between VN-100 group to control group was 1.31 (95% CI: 1.09-1.56). In all strains, the lower limit of the 95% CI exceeded the non-inferiority criterion, and the non-inferiority of VN-100 group to the control group was verified.

- The seroprotection rate of the HI antibody titer on Day 21 was 95.33% (429/450) in VN-100 group and 89.33% (402/450) in the control group in the H1N1 strain. Difference in seroprotection rate between VN-100 group to control group was 6.00% (95% CI: 2.54%-9.57%). - The seroprotection rate of the HI antibody titer on Day 21 was 96.22% (433/450) in VN-100 group and 92.00% (414/450) in the control group in the H3N2 strain. Difference in seroprotection rate between VN-100 group to control group was 4.22% (95% CI: 1.14%-7.42%). - The seroprotection rate of the HI antibody titer on Day 21 was 64.22% (289/450) in VN-100 group and 56.44% (254/450) in the control group in the B strain. Difference in seroprotection rate between VN-100 group to control group was 7.78% (95% CI: 1.39%-14.08%).

As a result of 1st intradermal vaccinated of VN-100 in healthy Japanese 65 years and older, seroconversion rate and GMT of HI antibody titer were confirmed to be good immunogenicity in any strain, and influenza HA vaccine non-inferiority for a 1st subcutaneous inoculation was verified. There were no serious safety problems in the safety of VN-100 group.

Oct. 29, 2015

https://www.sciencedirect.com/science/article/pii/S0264410X15015315

No

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DAIICHISANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

DAIICHISANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

April. 07, 2014

Interventional

A multicenter, randomized, active control, double blind, parallel-group study

prevention purpose

3

Healthy elderly Japanese volunteers

1) Subjects with history of seasonal influenza in the past 6 months
2) Subjects with history of seasonal influenza vaccination in the past 6 months

Both

Prophylaxis of influenza infection

investigational material(s)
Generic name etc : VN-100
INN of investigational material : -
Therapeutic category code : 631 Vaccines
Dosage and Administration for Investigational material : Intradermal

control material(s)
Generic name etc : Influenza HA vaccine
INN of investigational material : -
Therapeutic category code : 631 Vaccines
Dosage and Administration for Investigational material : subcutaneous injection

efficacy
The difference between the seroconversion rates and the ratio of GMTs of HI antibody titer against three vaccine stains at Day 21
To demonstrate the immunological non-inferiority in terms of the difference between the seroconversion rates (VN-100 seasonalinfluenza vaccine) and the ratio of GMTs (VN-100/seasonal influenza vaccine) of HI antibody titer against three vaccine stains at Day 21. The criteria are as follows.
1)The lower bound of the two-sided 95% CI on the difference between the seroconversion rates exceed -10 percentage points.
2)The lower bound of the two-sided 95% CI on the ratio of the GMTs exceed 2/3.
In case the non-inferiority is actually demonstrated, the following criteria regarding superiority are evaluated collaterally.

efficacy
Seroconversion rate, GMTs, and Seroprotection rate of HI antibody titer against three vaccine stains

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Mar. 20, 2014