A Phase 4 interventional study of Nasovac-S and Azithromycin in Influenza, sponsored by London School of Hygiene and Tropical Medicine. Completed at 1 site in Gambia. Open to participants aged 24 Months to 59 Months, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-02-21.
Sponsored by London School of Hygiene and Tropical Medicine · Phase 4, Interventional, and Prevention
The live attenuated influenza vaccine (LAIV) is made up of weakened influenza viruses given into the nose and in early studies was shown to be better than the standard influenza vaccine at preventing infections in children. However, more recently, it has performed less well and it may also work less well in Sub-Saharan Africa. Not only do the investigators not know why this is, but the investigators also do not fully understand why LAIV produces stronger nasal antibody responses in some individuals but not others. Usually harmless bacteria that are present in participants noses can influence how our immune system works and variations in these may explain differences in how LAIV works. The project will recruit children given LAIV in the Gambia to gain further understanding of these issues.
The investigators will measure a variety of responses to LAIV, including genes that can change their expression early after vaccination and use advanced computational techniques to identify new relationships between these genes and other LAIV responses. The investigators will also see whether nasal bacterial profiles in children who respond to LAIV are different from those who do not. In addition, the investigators will alter these bacteria in a subset of children with antibiotics and see whether this affects both nasal gene expression and later responses to LAIV.
Purpose The overall goal of this study is to conduct at detailed immunogenicity study of intranasal live attenuated influenza vaccine (LAIV; Nasovac-S, Serum Institute of India Pvt. Ltd.), including identification of early molecular signatures associated with a robust mucosal immune response. In addition, the study team will explore whether the nasopharyngeal microbiome influences this immune response and whether LAIV has an impact on the microbiome.
A total of 365 healthy children aged 24 - 59 months will be recruited in The Gambia for this study.
Background Both the burden of infection and use of influenza vaccines in children from sub-Saharan Africa (SSA) have been neglected. There are limited immunogenicity or efficacy data from SSA of the widely used Ann Arbor strain-derived LAIV. This LAIV was shown to have greater relative efficacy compared to inactivated influenza vaccine in children in early randomized-controlled trials. There has, however, been concern regarding lower vaccine effectiveness in the US in recent years.
The Serum Institute of India Pvt. Ltd. has recently developed a trivalent LAIV (Nasovac-S) via a WHO facilitated donation of a Russian-derived LAIV, with the intention of scaling up provision of LAIV to resource-limited settings. Based on initial safety and immunogenicity data, Nasovac-S was licensed in India and granted a WHO prequalification certificate in 2015. Two placebo-controlled efficacy studies using Nasovac-S were recently undertaken in Bangladesh and Senegal (in children aged 24 - 59 months and 24 - 71 months respectively), providing mixed and contrasting results. In Senegal, no efficacy was found against the circulating pandemic H1N1 influenza strain (-9.7%, 95% CI -62.6, 26.1). In Bangladesh the overall vaccine efficacy to vaccine-matched strains, in a study of identical design, was 57.5% (95% CI 43.6, 68.0), with efficacy against H1N1 and H3N2, 50.0% (95% CI 9.2, 72.5) and 60.4% (95% CI 44.8, 71.6) respectively. The reason for the discrepancy in these studies or the poorer performance of the H1N1 component is not clear and emphasizes the need to undertake detailed immunogenicity studies of this vaccine in SSA. On a wider note, the exact immunological mechanisms of action of LAIV are also under-explored.
Study type:
Interventional
Design:
All primary objectives will be addressed through the conduct of a phase 4, randomized, controlled clinical vaccine trial. A total of 330 healthy children aged 24 - 59 months will be enrolled into one of three groups of equal size (3 x 110 children):
(i) LAIV-vaccinated (Group A - blood sample at day 0, 2, 21) (ii) LAIV-vaccinated (Group B - blood sample at day 0, 7, 21) (iii) Control group (Group C)
The study is not blinded, but group allocation will be concealed from the investigator team and block randomization stratified by sex will be undertaken.
Two LAIV-vaccinated groups are included in order to achieve several exploratory objectives, which require blood sampling at different times following vaccination, whilst minimizing the number of times children are bled. The unvaccinated subjects will serve as a control group for the primary objective of assessing the impact of LAIV on the nasopharyngeal microbiome.
An additional 35 healthy children aged 24 - 59 months will be recruited in the 2nd phase of recruitment (approximately Jan - June 2018) to assess how modulation of the nasopharyngeal microbiome with antibiotics impacts the mucosal immunogenicity to LAIV. These subjects will be matched as closely as possible by pre-antibiotic nasopharyngeal microbiome profile, age and sex (in that order of preference), in an exploratory nested case-control study, to n = 35 children recruited in the main clinical trial.
Official title A Study of Intranasal Live Attenuated Influenza Vaccine Immunogenicity and Associations with the Nasopharyngeal Microbiome Among Children in the Gambia (The NASIMMUNE study)
Primary outcome measures
2,356 studies on the registry are indexed under Influenza, Human; 184 are open to participants now.
This study's enrollment of 364 is above the median of 227 across 1,957 interventional studies indexed under Influenza, Human.
Browse Influenza, Human studies →London School of Hygiene and Tropical Medicine is the lead sponsor of 298 studies on the registry; 15 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Healthy male or female child at least 24 months of age and less than 60 months of age at the time of study entry.
Exclusion Criteria:
Serious, active, medical condition, including but not limited to:
known genetic disorders, such as Down's syndrome or other cytogenetic disorder
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The human immunodeficiency virus, which weakens the immune system.
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Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
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A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
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Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Nasovac-S vaccination group A , blood samples days 0, 2, 21
Biological: Nasovac-S
Nasovac-S vaccination group B, blood samples at days 0, 7, 21
Biological: Nasovac-S
control group C
group D - a single dose of oral Azithromycin will be given 28 days prior to Nasovac-S vaccination
Biological: Nasovac-S · Drug: Azithromycin
one of 0.5ml intranasal dose of trivalent live attenuated vaccine (LAIV)
a single dose of Azithromycin (liquid formulation - Zithromax) at 20mg/Kg (up to a maximum adult dose 1g) to be given to a subset of subjects
Also known as: Zithromax
nasal IgA response
Influenza specific nasal IgA responses
Time frame: 21 days post LAIV
fold increase in oral fluid influenza-specific/total IgA ratio
Time frame: day 0 - Day 21
fold increase in oral fluid influenza-specific/total IgG ratio
Time frame: Day 0 - Day 21
density of S. Pneumoniae
density of S. Pneumoniae before and after LAIV as established by quantitative PCR
Time frame: day 7 and day 21 after LAIV compared to day 0
Changes in the relative abundance of different operational taxanomic units (OTUs) of nasopharyngeal microbiota
Time frame: day 7 and day 21 compared to day 0 in each participant
gene expression changes in nasal and systemic samples
Time frame: 2 days after LAIV
Plan to share: No
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Studies of the drug tested here: Azithromycin
London School of Hygiene and Tropical Medicine →