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

NCT04669691 | Completed Phase 2 Results

• 2 other identifiers: V87_302016-001898-32
• Study Type: interventional
• Target: 420
• Locations: 2 countries
• Sites: 7

Brief Summary

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

Conditions

Influenza, Human

Keywords

Pandemic; Influenza; Vaccine; MF59; Adjuvant

Outcome Measures

Primary Outcomes (7)

• 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

• 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

Secondary Outcomes (4)

• Secondary Immunogenicity Endpoint 1a: GMTs, as Measured by HI and MN Assays Against the Homologous H5N1 Strain

  Day 1 (baseline) and Day 202

• Secondary Immunogenicity Endpoint 1b: GMRs, as Measured by HI and MN Assays Against the Homologous H5N1 Strain

  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)

  Day 1 (baseline) and Day 202

• Secondary Immunogenicity Endpoint 1d: Percentage of Subjects Achieving Seroconversion With a Titer ≥1:40

  Day 1 (baseline) and Day 202

Study Arms (6)

Lowest dose, less adjuvant aH5N1 vaccine

EXPERIMENTAL

Two consecutive intramuscular (IM) administrations (Day 1 and Day 22)

Biological: H5N1 antigen combined with MF59 adjuvant

Low dose, less adjuvant aH5N1 vaccine

EXPERIMENTAL

Two consecutive IM administrations (Day 1 and Day 22)

Biological: H5N1 antigen combined with MF59 adjuvant

Mid dose, less adjuvant aH5N1 vaccine

EXPERIMENTAL

Two consecutive IM administrations (Day 1 and Day 22)

Biological: H5N1 antigen combined with MF59 adjuvant

Lowest dose, adjuvanted aH5N1 vaccine

EXPERIMENTAL

Two consecutive IM administrations (Day 1 and Day 22)

Biological: H5N1 antigen combined with MF59 adjuvant

Low dose, adjuvanted aH5N1 vaccine

EXPERIMENTAL

Two consecutive IM administrations (Day 1 and Day 22)

Biological: H5N1 antigen combined with MF59 adjuvant

Mid dose, adjuvanted aH5N1 vaccine

EXPERIMENTAL

Two consecutive IM administrations (Day 1 and Day 22)

Biological: H5N1 antigen combined with MF59 adjuvant

Interventions

H5N1 antigen combined with MF59 adjuvant BIOLOGICAL

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

Also known as: aH5N1

Low dose, adjuvanted aH5N1 vaccine; Low dose, less adjuvant aH5N1 vaccine; Lowest dose, adjuvanted aH5N1 vaccine; Lowest dose, less adjuvant aH5N1 vaccine; Mid dose, adjuvanted aH5N1 vaccine; Mid dose, less adjuvant aH5N1 vaccine

Eligibility Criteria

• Age: 6 Months - 8 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy male and female subjects of 6 months through \<9 years of age on the day of informed consent/assent.
• 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.
• 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.
• Subjects must provide a baseline blood sample within 10 days prior to the Day 1 vaccination.

You may not qualify if:

• Each subject must not have:
• Progressive, unstable or uncontrolled clinical conditions.
• Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
• Clinical conditions representing a contraindication to intramuscular vaccination and blood draws, ie,
• 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.
• History of epilepsy or convulsions (excluding febrile convulsions).
• A subject who has any medical condition meeting the definition of AESI defined for the purposes of this trial (see appendix A).
• 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.
• Abnormal function of the immune system resulting from:
• Clinical conditions.
• 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.
• Administration of antineoplastic and immunomodulating agents or radiotherapy from within 90 days prior to informed consent/assent.
• Suspicion of pandemic influenza illness within past six months or have ever received previous pandemic H5N1 flu vaccination.
• Received immunoglobulins or any blood products within 180 days prior to informed consent/assent.
• Received an investigational or non-registered medicinal within 30 days prior to informed consent/assent.

Sponsors & Collaborators

• Seqirus: lead

Study Sites (7)

23302- Al Mare Perearstikeskus OÜ

Tallinn, Harju, 10617, Estonia

Location

23301- Clinical Research Center

Tartu, Tartu, 50106, Estonia

Location

60805 - De La Salle Medical and Health Sciences Institute

Dasmariñas, Manila, 4114, Philippines

Location

60804 - University of Perpetual Help Dalta Medical Center

Las Piñas, Manila, 1742, Philippines

Location

60802- Philippine General Hospital

Manila, National Capital Region, 1000, Philippines

Location

60803- Philippine General Hospital - Pediatrics

Manila, National Capital Region, 1000, Philippines

Location

60801- Philippine General Hospital - Pediatrics

Manila, 1000, Philippines

Location

Related Publications (2)

• 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.

  PMID: 20819892 BACKGROUND

• 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.

  PMID: 22777094 BACKGROUND

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Seqirus Clinical Trial Manager
• Organization: Seqirus

seqirus.clinicaltrials@Seqirus.com

1-855-358-8966

Study Officials

• Clinical Program Manager

  Seqirus

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: December 17, 2020
• Study Start: December 19, 2020
• Primary Completion: April 15, 2022
• Study Completion: April 15, 2022
• Last Updated: March 13, 2024
• Results First Posted: January 16, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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

Locations

PH (5); ES (2)