Ignite Creation Date:
2025-12-24 @ 8:03 PM
Ignite Modification Date:
2026-01-01 @ 5:17 AM
Study NCT ID:
NCT02529904
Status:
COMPLETED
Last Update Posted:
2023-12-07
First Post:
2015-08-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
ADITEC FLU 2 STUDY: Understanding the Genetics Basis for Immune Responses to Flu Vaccines in Children and Adults
Sponsor:
University of Oxford
Organization:
Study Overview
Official Title:
A Phase II, Open Label Study to Describe Immune & Transcriptional Responses to MF59 Adjuvanted Trivalent Influenza Vaccine (ATIV) in Healthy 13-24 Month Children and Adults 18-65 Years
Status:
COMPLETED
Status Verified Date:
2018-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Influenza infection is related to significant morbidity and mortality in children. The trivalent inactive vaccine (TIV) has been documented to have poor immunogenicity in children and the live attenuated influenza vaccine (ATIV) although proven to have more efficacy is unable to be administered to children under 2 years old. The MF59 adjuvanted influenza vaccine as proven efficacy on reducing the rates of laboratory confirmed influenza, including in children.
The study aims to assess early gene transcriptional responses to priming and boosting with MF59-ATIV in children aged 13-24 months and adults aged 18 - 65 years, and to establish correlations with haemagglutination inhibition (HAI) titers. It will be an open label study with 90 healthy children allocated to 3 groups (groups 1, 2 and 3) and 30 healthy adults allocated to group 4.
The study aims to assess early gene transcriptional responses to priming and boosting with MF59-ATIV in children aged 13-24 months and adults aged 18 - 65 years, and to establish correlations with haemagglutination inhibition (HAI) titers. It will be an open label study with 90 healthy children allocated to 3 groups (groups 1, 2 and 3) and 30 healthy adults allocated to group 4.
Detailed Description:
Influenza infection is related to significant morbidity and mortality in children. The commonly used trivalent inactive influenza vaccine (TIV) has been documented to have poor immunogenicity in children, particularly in those less than 2 years old. The live attenuated influenza vaccine (LAIV) has shown improved efficacy compared to TIV, however LAIV is unable to be administered to children under 2 years old and those with contraindications, hence an effective alternative is required.
The focus toward adjuvanted influenza vaccines for children, particularly the MF59 adjuvant, has shown promising results in relation to safety and efficacy. This study aims to further explore the MF59 adjuvanted influenza vaccine from a gene expression perspective using a systems biology approach and relate these findings to innate immune responses, immunogenicity and reactogenicity.
The MF-59 adjuvant was approved for human use in 1997 and was studied initially in the elderly and more recently in children as young as 6 months. MF59-ATIV (Fluad®, Gripguard® (France) and Chiromas® (Spain)) is approved in Europe for adults aged 65 years and over and has been administered to over 5000 children in clinical trials.
In a recent large study with over 4000 children aged 6 months to 72 months, MF59-ATIV significantly reduced rates of laboratory-confirmed influenza with an absolute efficacy of 86%, demonstrating this vaccine to be an effective option for vaccinating children less than 2 years old unable to have the live attenuated vaccine. Unpublished data from the ADITEC Flu pilot study conducted in 2012 (EudraCT Number: 2012-002443-26, Ethics Ref: OxREC C 12/SC/0407); a phase 2, randomised, open label study, also demonstrated increased immunogenicity and a relatively similar reactogenicity profile following ATIV immunisation compared to TIV.
This study will use a systems biology approach to identify early gene signatures that relate to common innate and adaptive immune pathways following priming and boosting with ATIV, and to correlate these results with HAI response in children and adults.The systems biology approach has been used previously in vaccine research to identify gene module expression, including studies focusing on description of gene expression following the yellow fever vaccine (YF-17D), LAIV and TIV in adults. The study aims to assess early gene transcriptional responses to priming and boosting with MF59-ATIV in children aged 13-24 months and adults aged 18 - 65 years, and to establish correlations with HAI titers. It will be an open label study with 90 healthy children allocated to 3 groups (groups 1, 2 and 3) and 30 healthy adults allocated to group 4. Each participant will have an initial visit where screening will be completed and informed consent taken. The participant will then be enrolled and allocated a study participant number at this time. This initial visit ('Screening visit') will occur within the 56 days prior to the first ATIV immunisation. Group allocation will occur at or after the screening visit. Each child will receive 2 doses of ATIV and adults will receive 1 dose. ATIV is not currently licensed for children, and looking to previous studies, ATIV has been given to children less than 36 months as two 0.25 ml injections 4 weeks apart, and we will follow that immunisation schedule in this study. The timing of blood samples to be taken during the study will differ for each group in order to minimise number of blood collections per child but still enable assessment of gene expression and immune response at multiple time points.
The focus toward adjuvanted influenza vaccines for children, particularly the MF59 adjuvant, has shown promising results in relation to safety and efficacy. This study aims to further explore the MF59 adjuvanted influenza vaccine from a gene expression perspective using a systems biology approach and relate these findings to innate immune responses, immunogenicity and reactogenicity.
The MF-59 adjuvant was approved for human use in 1997 and was studied initially in the elderly and more recently in children as young as 6 months. MF59-ATIV (Fluad®, Gripguard® (France) and Chiromas® (Spain)) is approved in Europe for adults aged 65 years and over and has been administered to over 5000 children in clinical trials.
In a recent large study with over 4000 children aged 6 months to 72 months, MF59-ATIV significantly reduced rates of laboratory-confirmed influenza with an absolute efficacy of 86%, demonstrating this vaccine to be an effective option for vaccinating children less than 2 years old unable to have the live attenuated vaccine. Unpublished data from the ADITEC Flu pilot study conducted in 2012 (EudraCT Number: 2012-002443-26, Ethics Ref: OxREC C 12/SC/0407); a phase 2, randomised, open label study, also demonstrated increased immunogenicity and a relatively similar reactogenicity profile following ATIV immunisation compared to TIV.
This study will use a systems biology approach to identify early gene signatures that relate to common innate and adaptive immune pathways following priming and boosting with ATIV, and to correlate these results with HAI response in children and adults.The systems biology approach has been used previously in vaccine research to identify gene module expression, including studies focusing on description of gene expression following the yellow fever vaccine (YF-17D), LAIV and TIV in adults. The study aims to assess early gene transcriptional responses to priming and boosting with MF59-ATIV in children aged 13-24 months and adults aged 18 - 65 years, and to establish correlations with HAI titers. It will be an open label study with 90 healthy children allocated to 3 groups (groups 1, 2 and 3) and 30 healthy adults allocated to group 4. Each participant will have an initial visit where screening will be completed and informed consent taken. The participant will then be enrolled and allocated a study participant number at this time. This initial visit ('Screening visit') will occur within the 56 days prior to the first ATIV immunisation. Group allocation will occur at or after the screening visit. Each child will receive 2 doses of ATIV and adults will receive 1 dose. ATIV is not currently licensed for children, and looking to previous studies, ATIV has been given to children less than 36 months as two 0.25 ml injections 4 weeks apart, and we will follow that immunisation schedule in this study. The timing of blood samples to be taken during the study will differ for each group in order to minimise number of blood collections per child but still enable assessment of gene expression and immune response at multiple time points.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: