A Dose-ranging Pediatric Study of an Adjuvanted Pandemic Influenza Vaccine

A Phase 2, Randomized, Observer-Blind, Multicenter Study to Evaluate the Immunogenicity and Safety of Several Doses of Antigen and MF59 Adjuvant Content in a Monovalent H5N1 Pandemic Influenza Vaccine in Healthy Pediatric Subjects 6 Months to < 9 Years of Age

This study is a pediatric dose-ranging study to evaluate the safety and immunogenicity of vaccination with different MF59-adjuvanted H5N1 vaccine formulations.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Biological: H5N1 antigen combined with MF59 adjuvant

• Study Type: Interventional
• Enrollment (Actual): 420
• Phase: Phase 2

Contacts and Locations

Study Locations

• Estonia
  • Harjumaa
    • Tallinn, Harjumaa, Estonia, 10617
      • 23302- Al Mare Perearstikeskus OÜ
  • Tartumaa
    • Tartu, Tartumaa, Estonia, 50106
      • 23301- Clinical Research Center
• Philippines
  • Manila, Philippines, 1000
    • 60801- Philippine General Hospital - Pediatrics
  • Manila
    • Dasmarinas, Manila, Philippines, 4114
      • 60805 - De La Salle Medical and Health Sciences Institute
    • Las Piñas, Manila, Philippines, 1742
      • 60804 - University of Perpetual Help Dalta Medical Center
  • National Capital Region
    • Manila, National Capital Region, Philippines, 1000
      • 60802- Philippine General Hospital
    • Manila, National Capital Region, Philippines, 1000
      • 60803- Philippine General Hospital - Pediatrics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 8 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy male and female subjects of 6 months through <9 years of age on the day of informed consent/assent.
2. Documented consent provided by the subject's parent(s)/LAR(s) have voluntarily given written informed consent/assent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
3. Subject's parent(s)/LAR(s) able to comprehend and comply with all study procedures, and available for all clinic visits and telephone contacts scheduled in the study.
4. Subjects must provide a baseline blood sample within 10 days prior to the Day 1 vaccination.

Exclusion Criteria:

Each subject must not have:

1. Progressive, unstable or uncontrolled clinical conditions.
2. Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.

3. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws, ie,

   1. Subjects who have had a fever (body temperature measurement ≥ 38°C) within three days prior to vaccination. The subject may return for vaccination after they have been free of fever for three days.
   2. History of epilepsy or convulsions (excluding febrile convulsions).
   3. A subject who has any medical condition meeting the definition of AESI defined for the purposes of this trial (see appendix A).
   4. Subjects who have received antipyretic medication within the past 24 hours prior to vaccination. The subject may return for vaccination after a period of 24 hours has passed since the administration of an antipyretic.

4. Abnormal function of the immune system resulting from:

   1. Clinical conditions.
   2. Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to informed consent/assent. Topical, inhaled and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids are also permitted.
   3. Administration of antineoplastic and immunomodulating agents or radiotherapy from within 90 days prior to informed consent/assent.
5. Suspicion of pandemic influenza illness within past six months or have ever received previous pandemic H5N1 flu vaccination.
6. Received immunoglobulins or any blood products within 180 days prior to informed consent/assent.
7. Received an investigational or non-registered medicinal within 30 days prior to informed consent/assent.
8. Children of study site staff (this includes research or clinic staff) or children who are otherwise related to study site staff or have household members who are study site staff. Study site staff are employees with direct or indirect contact with study subjects and/or have access to any study documents containing subject information. This would include receptionists, persons scheduling appointments or making screening calls, regulatory specialists, laboratory technicians, medical assistants, document scanners, etc. study personnel as an immediate family or household member.
9. Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study.
10. Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrolment in this study or who are planning to receive any vaccine prior to day 43. Following day 43 other vaccines may be administered, including seasonal flu.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lowest dose, less adjuvant aH5N1 vaccine; Two consecutive intramuscular (IM) administrations (Day 1 and Day 22)	Biological: H5N1 antigen combined with MF59 adjuvant; Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart; Other Names: aH5N1
Experimental: Low dose, less adjuvant aH5N1 vaccine; Two consecutive IM administrations (Day 1 and Day 22)	Biological: H5N1 antigen combined with MF59 adjuvant; Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart; Other Names: aH5N1
Experimental: Mid dose, less adjuvant aH5N1 vaccine; Two consecutive IM administrations (Day 1 and Day 22)	Biological: H5N1 antigen combined with MF59 adjuvant; Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart; Other Names: aH5N1
Experimental: Lowest dose, adjuvanted aH5N1 vaccine; Two consecutive IM administrations (Day 1 and Day 22)	Biological: H5N1 antigen combined with MF59 adjuvant; Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart; Other Names: aH5N1
Experimental: Low dose, adjuvanted aH5N1 vaccine; Two consecutive IM administrations (Day 1 and Day 22)	Biological: H5N1 antigen combined with MF59 adjuvant; Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart; Other Names: aH5N1
Experimental: Mid dose, adjuvanted aH5N1 vaccine; Two consecutive IM administrations (Day 1 and Day 22)	Biological: H5N1 antigen combined with MF59 adjuvant; Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart; Other Names: aH5N1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Endpoint 3: Percentages of Subjects Reporting Serious Adverse Events (SAEs), New-onset Chronic Disease (NOCD), Adverse Events of Special Interest (AESI), and AEs Leading to Vaccine and/or Study Withdrawal	Percentages of subjects reporting SAEs, NOCDs, AESIs, and AEs leading to vaccine and/or study withdrawal, as collected from Day 1 through Day 387, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.	Day 1 through Day 387
Primary Immunogenicity Endpoint 1a: Geometric Mean Titers (GMTs), as Measured by Hemagglutination Inhibition (HI) and Microneutralization (MN) Assays Against the Homologous H5N1 Strain	GMTs on Day 1 (prior to the first vaccination), Day 22 (3 weeks after the first vaccination), and Day 43 (3 weeks after the second vaccination) as determined by HI and MN assays against the homologous H5N1 pandemic influenza strain, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.	Day 1 (baseline), Day 22, and Day 43
Primary Immunogenicity Endpoint 1b: Geometric Mean Ratios (GMR), as Measured by HI and MN Assays Against the Homologous H5N1 Strain	GMRs calculated as follows: Day 22/Day 1 and Day 43/Day 1 as determined by HI and MN assays against the homologous H5N1 pandemic influenza strain, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.	Day 1 (baseline), Day 22, and Day 43
Primary Immunogenicity Endpoint 1c: Percentage of Subjects Achieving Seroconversion (Non-detectable to ≥1:40, or 4-fold Increase From a Detectable Day 1 Titer)	Percentage of subjects achieving seroconversion (non-detectable to ≥1:40, or 4-fold increase from a detectable Day 1 titer) on Day 22 and Day 43 as determined by HI and MN assays against the homologous H5N1 pandemic influenza strain, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.	Day 1 (baseline), Day 22, and Day 43
Primary Immunogenicity Endpoint 1d: Percentage of Subjects Achieving Seroconversion With a Titer ≥1:40	Percentage of subjects achieving seroconversion with a titer ≥1:40 on Day 1, Day 22, and Day 43 as determined by HI and MN assays against the homologous H5N1 pandemic influenza strain, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.	Day 1 (baseline), Day 22, and Day 43
Safety Endpoint 1: Percentages of Subjects With Solicited Local and Systemic Adverse Events (AEs)	Percentages of subjects with solicited local and systemic AEs that occurred within 7 days following each vaccination, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.	Day 1 through Day 7 and Day 22 through Day 28
Safety Endpoint 2: Percentages of Subjects With Any Unsolicited AEs	Percentages of subjects with any unsolicited AEs reported within 21 days after each vaccination within each vaccine group, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.	Day 1 through Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Immunogenicity Endpoint 1a: GMTs, as Measured by HI and MN Assays Against the Homologous H5N1 Strain	GMTs on Day 1 (prior to the first vaccination) and Day 202 (6 months after the second vaccination) as determined by HI and MN assays against the homologous H5N1 pandemic influenza strain, by total population and by age cohort.	Day 1 (baseline) and Day 202
Secondary Immunogenicity Endpoint 1b: GMRs, as Measured by HI and MN Assays Against the Homologous H5N1 Strain	GMRs calculated as follows: Day 202/Day 1 as determined by HI and MN assays against the homologous H5N1 pandemic influenza strain, by total population and by age cohort.	Day 1 (baseline) and Day 202
Secondary Immunogenicity Endpoint 1c: Percentage of Subjects Achieving Seroconversion (Non-detectable to ≥1:40, or 4-fold Increase From a Detectable Day 1 Titer)	Percentage of subjects achieving seroconversion (non-detectable to ≥1:40, or 4-fold increase from a detectable Day 1 titer) on Day 202 as determined by HI and MN assays against the homologous H5N1 pandemic influenza strain, by total population and by age cohort.	Day 1 (baseline) and Day 202
Secondary Immunogenicity Endpoint 1d: Percentage of Subjects Achieving Seroconversion With a Titer ≥1:40	Percentage of subjects achieving seroconversion with a titer ≥1:40 on Day 1 and Day 202 as determined by HI and MN assays against the homologous H5N1 pandemic influenza strain, by total population and by age cohort.	Day 1 (baseline) and Day 202

Collaborators and Investigators

• Sponsor: Seqirus
• Investigators: Study Director: Clinical Program Manager, Seqirus

Publications and helpful links

General Publications

• Vesikari T, Karvonen A, Tilman S, Borkowski A, Montomoli E, Banzhoff A, Clemens R. Immunogenicity and safety of MF59-adjuvanted H5N1 influenza vaccine from infancy to adolescence. Pediatrics. 2010 Oct;126(4):e762-70. doi: 10.1542/peds.2009-2628. Epub 2010 Sep 6.
• Vesikari T, Forsten A, Borkowski A, Gaitatzis N, Banzhoff A, Clemens R. Homologous and heterologous antibody responses to a one-year booster dose of an MF59((R)) adjuvanted A/H5N1 pre-pandemic influenza vaccine in pediatric subjects. Hum Vaccin Immunother. 2012 Jul;8(7):921-8. doi: 10.4161/hv.20248. Epub 2012 Jul 1.

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2020
• Primary Completion (Actual): April 15, 2022
• Study Completion (Actual): April 15, 2022

Study Registration Dates

• First Submitted: November 30, 2016
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Influenza; Vaccine; Adjuvant; Pandemic; MF59
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: V87_30; 2016-001898-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

SEQIRUS supports the release of anonymized subject-level and study-level data in compliance with regulatory requirements, including Clinical Documents which are part of the CTD modules submitted to regulatory agencies for public release.

Summary results disclosure is either in document form (e.g., ICH E3 Clinical Study Report synopsis) or structured data form (such as summary results in ClinicalTrials.gov (United States) or eudract.ema.europa.eu (EU Clinical Trial Registry [EU CTR])

• IPD Sharing Time Frame: SEQIRUS discloses results from clinical studies within 12 months of last patient last visit (LPLV) unless otherwise mandated by local laws or regulations.
• IPD Sharing Access Criteria: SEQIRUS will consider requests from qualified scientific and medical researchers to disclose protocols, anonymized subject-level data and study-level data when there is medical, scientific and/or public health interest to ensure the safe use of a Seqirus product licensed on or after 1 January 2014 in the United States (US) and/or the European Union (EU). This applies to Seqirus-sponsored interventional studies initiated after 27 September 2007 and ongoing as of 26 December 2007, that have been included as part of a US or EU submission package which received approval in US and EU on or after 1 January 2014 and have been accepted for publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No