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A Phase 3, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of MEDI3250 Compared to Placebo in Healthy Japanese Children age 2 years through 18 years

914

The demographics and baseline characteristics in per protocol set (PPS) is as follows. The proportion of male subjects was 50.8% (302/595) in the MEDI3250 group and 49.7% (144/290) in the placebo group, and that of female subjects was 49.2% (293/595) in the MEDI3250 group and 50.3% (146/290) in the placebo group. The mean age was 8.2 years in the MEDI3250 group and 8.0 years in the placebo group. The proportion of subjects aged 2 to 6 years was 38.0% (226/595) in the MEDI3250 group and 37.2% (108/290) in the placebo group. The proportion of subjects aged 7 to 18 years was 62.0% (369/595) in the MEDI3250 group and 62.8% (182/290) in the placebo group. History of influenza incidence in the 2015/16 season was 31.8% (189/595) in the MEDI3250 group and 32.8% (95/290) in the placebo group. History of influenza vaccination in 2015/16 season was 42.7% (254/595) in the MEDI3250 group and 44.8% (130/290) in the placebo group, and history of influenza vaccination within the past 5 years was 68.4% (407/595) in the MEDI3250 group and 68.6% (199/290) in the placebo group.

A total of 914 subjects were enrolled in this study and 3 subjects were withdrawn from the screening. There were 911 randomized subjects (MEDI3250 group, 609 subjects; placebo group, 302 subjects), of whom 1 who was assigned to the MEDI3250 group was excluded from the safety analysis set because he did not receive the study drug, and the safety analysis set was 910 subjects (608 subjects, 302 subjects). PPS consisted of 885 subjects (595 subjects, 290 subjects). Twenty-six subjects (14 subjects, 12 subjects) were excluded from the PPS. Reasons for exclusion were ineligibility for efficacy assessment (11 subjects, 10 subjects), violation of the exclusion criteria (2 subjects, 2 subjects), and unvaccinated subjects (1 subject, 0 subject). Efficacy was evaluated by PPS.

The incidence of solicited adverse events (pyrexia>=38 degree, runny nose/stuffy nose, sore throat, cough, headache, generalized myalgia, decreased activity (lethargy) or fatigue/weakness, decreased appetite) that occurred within 14 days after study drug administration was 72.5% (441/608) in the MEDI3250 group and 68.9% (208/302) in the placebo group. The incidence of specific events was runny nose/stuffy nose (MEDI3250 group: 63.8%, placebo group: 58.6%, respectively), cough (33.4%, 41.7%), sore throat (21.5%, 21.5%), headache (14.6%, 14.2%), pyrexia>=38 degree (9.9%, 7.9%), decreased activity (lethargy) or fatigue/weakness (9.0%, 8.6%), decreased appetite (8.4%, 8.3%), generalized myalgia (3.0%, 1.7%). The incidence of the study drug-related solicited adverse events was runny nose/stuffy nose (59.2%, 52.6%), cough (27.8%, 36.8%), sore throat (17.9%, 17.2%), headache (11.2%, 10.6%), decreased activity (lethargy) or fatigue/weakness (6.6%, 5.6%), pyrexia>=38 degree (5.9%, 3.0%), decreased appetite (5.4%, 6.0%), generalized myalgia (1.8%, 0.7%). The incidence of adverse events (excluding solicited adverse events) that occurred within 28 days after study drug administration was 36.0% (219/608) in the MEDI3250 group and 33.1% (100/302) in the placebo group, and the incidence was higher (at least 2% in either of the inoculation groups) in the nasopharyngitis (MEDI3250 group: 7.7%, placebo group: 9.9%, respectively), inflammation of the upper respiratory tract (4.4%, 2.3%), bronchitis (3.1%, 3.6%), and diarrhea (3.0%, 3.0%), gastroenteritis (2.8%, 2.6%), influenza (2.1%, 0.7%), abdominal pain (2.0%, 2.3%), and vomiting (2.0%, 1.7%). The incidence of adverse drug reactions (excluding solicited adverse drug reactions) was 8.9% (54/608) in the MEDI3250 group and 8.3% (25/302) in the placebo group. Common adverse drug reactions (incidence of at least 1% in either of the inoculation groups) and their incidences were diarrhea (MEDI3250 group: 2.3%, placebo group: 2.3%, respectively), influenza (1.8%, 0%), nasopharyngitis (1.0%, 1.7%), abdominal pain (1.0%, 1.0%), pyrexia (0.8%, 1.0%), and epistaxis (0.7%, 1.0%).

The incidence of influenza caused by all wild type strains of influenza virus that showed symptoms of influenza infection and were not antigenically consistent with vaccine strains was 25.5% (152/595) in the MEDI3250 group and 35.9% (104/290) in the placebo group, and the relative risk reduction (95% confidence interval, CI) for the placebo group was 28.8% (12.5-42.0). The lower bound of the 95% CI was above 0 to validate the superiority of MEDI3250 over placebo. Of the influenza virus strains identified, the A/H3N2 subtype accounted for 83% of the total population in both the inoculation groups, and the relative risk reduction (95% CI) was 28.0% (9.0-43.1). MEDI3250 showed significant efficacy for the placebo.

The proportion of subjects with influenza symptoms during the influenza crisis investigation period who were confirmed to be caused by the wild strain of the influenza virus whose antigenicity matched the vaccine strain was 10.9% (65/595) in the MEDI3250 group and 17.2% (50/290) in the placebo group, and the relative risk reduction (95% CI) was 36.6% (6.5-56.8) relative to the placebo group. Significant efficacy of MEDI3250 over placebo was confirmed. The relative risk reduction (95% CI) of the A/H3N2 subtype to the placebo group was 41.0% (6.8-62.4), and MEDI3250 showed significant efficacy for the placebo. The incidence of influenza due to symptoms according to the modified CDC-ILI (influenza-like illness) definitions (pyrexia≥37.6℃ plus one or more of cough, sore throat, nasal discharge/nasal obstruction) and all wild strains of influenza virus regardless of antigen concordance with the vaccine strain was 21.3% (127/595) in the MEDI3250 group and 30.7% (89/290) in the placebo group. The relative risk reduction (95% CI) was 30.5% (12.3-44.8) relative to the placebo group, and the significant efficacy of MEDI3250 compared to the placebo was also confirmed in subjects with symptoms according to the modified CDC-ILI definitions. The proportion of subjects with influenza symptoms according to the modified CDC-ILI definitions who were laboratory-identified as being caused by the wild strain of the influenza virus whose antigenicity matched the vaccine strain was 9.1% (54/595) in the MEDI3250 group and 15.5% (45/290) in the placebo group. The relative risk reduction (95% CI) was 41.5% (11.1 to 61.4) relative to the placebo group, and the significant efficacy of MEDI3250 compared to the placebo was also confirmed in subjects with symptoms according to the modified CDC-ILI definitions.

The incidence of symptoms of influenza infection and onset of influenza identified by testing to be due to any wild-type influenza virus regardless of antigen matching with vaccine strain was 25.5% (152/597) in the MEDI3250 group and 35.9% (104/290) in the placebo group. The relative risk reduction (95% CI) versus the placebo group was 28.8% (12.5-42.0), verifying the superiority of single vaccination with MEDI3250 over placebo in terms of preventing influenza onset in children 2 to <19 years old.

June. 30, 2023

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

Interventional

Multicenter, randomized, placebo-controlled double-blind study

3

1) Healthy Japanese Children age 2 years through 18 years at the time of informed consent.
2) The ability of the subject to give to comply with study procedures and performed any study-specific procedure, to offer any symptom.

1) Administration of any influenza virus vaccine within 6 months prior to informed consent.
2) Use of antiviral agents with activity against influenza virus within 28 days prior to informed consent.

Both

Prophylaxis of influenza infection

investigational material(s)
Generic name etc : MEDI3250
INN of investigational material :
Therapeutic category code : 631 Vaccines
Dosage and Administration for Investigational material : Intranasal administration was 0.1 mL per nostril.(total 0.2mL)

control material(s)
Generic name etc : placebo
INN of investigational material :
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Intranasal administration was 0.1 mL per nostril.(total 0.2mL)

1)Efficacy
The incidence of laboratory-confirmed symptomatic influenza infection caused by any community-acquired wild-type strains regardless of match to the vaccine.
2) Safety
Incidence of treatment-emergent adverse events
-Solicited adverse events for 14 days post vaccination
-Adverse events for 28 days post vaccination
-Serious adverse events from informed consent until the end of the study.
The endpoint is evaluated by constructing a 2-sided 95% exact confidence interval for the risk reduction of MEDI3250 compared to placebo.

The incidence of wild type influenza infection from the genotyping test, caused by vaccine-matched strain in the influenza surveillance period.
The endpoint is evaluated by constructing a 2-sided 95% exact confidence interval for the risk reduction of MEDI3250 compared to placebo.