GEneRating Mucosal Immunity After INfluenzA Infection and Vaccination in Lung and Lymphoid TissuE

Официальное название

A Two-arm, Non-randomised, Open-label Experimental Medicine Study to Compare Immune Responses Between Healthy Volunteers Aged 18-55years Receiving Either an Intranasal Live-attenuated Influenza Vaccine or Viral Challenge With GMP Influenza A/Belgium/4217/2015 (H3N2)

Обзор

This experimental medicine study aims to compare immune responses in healthy adult volunteers aged 18-55 years against influenza vaccination and infection in the upper and lower respiratory tract, following administration of a live-attenuated influenza vaccine delivered by nasal spray versus influenza A (H3N2) viral challenge.

Вмешательства

• Биопрепарат FLUENZ
  LAIV (Intranasal Influenza Vaccine)
• Биопрепарат Influenza challenge virus
  Influenza challenge virus (H3N2 strain)

Первичные конечные точки

• Peak symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-55 [Срок оценки: 14 days]
• Average duration of symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-55 [Срок оценки: 14 days]
• To confirm symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-55 by Area Under the Curve [Срок оценки: 14 days]
• Peak symptoms related to inoculation with LAIV in healthy adults aged 18-55 [Срок оценки: 14 days]
• Average duration of symptoms related to inoculation with LAIV in healthy adults aged 18-55 [Срок оценки: 14 days]
• To confirm symptoms related to inoculation with LAIV in healthy adults aged 18-55 by Area Under the Curve [Срок оценки: 14 days]

Вторичные конечные точки (4)

• To assess influenza viral dynamics in upper respiratory samples [Срок оценки: 28 days]
• To assess antibody levels in blood before and after influenza challenge infection [Срок оценки: 28 days]
• To assess LAIV viral dynamics by RT-PCR in upper respiratory samples [Срок оценки: 28 days]
• To assess antibody levels in blood before and after LAIV [Срок оценки: 28 days]

Критерии участия

Критерии включения

• Adults aged between 18-55 years inclusive
• Sero-suitable as defined by a serum micro-neutralisation titre <1:20
• Female participant who is not of child-bearing potential as assessed by an investigator OR is willing and able to use contraception as described in the protocol
• Male participants who are willing to use one of the contraception methods described in the protocol
• In good health with no clinically significant medical conditions

Критерии исключения

• History of clinically significant/currently active conditions;

• Cardiovascular, thromboembolic/cerebrovascular disease.
• Types of chronic respiratory disease in adulthood.
• Significant wheeze in the past
• Respiratory symptoms including wheeze, resulting in hospitalisation
• Known bronchial hyperactivity to viruses
• Diabetes mellitus
• Migraine with associated symptoms like hemiplegia/vision loss. Cluster headache/migraine/prophylactic treatment for migraine.
• History of autoimmune disease/known immunodeficiency of any cause
• Immunosuppression.
• Known coagulation disorder/anticoagulant therapy
• Psychiatric illness including participants with a history of depression and/or anxiety with associated psychiatric comorbidities
• Other major disease that, under the PI's discretion, could interfere with the participant completing the study.
• Concurrent serious illness including history of malignancy that could interfere with the study or a participant completing the study.
• Known IgA deficiency/immotile cilia syndrome/Kartagener's syndrome
• Significant abnormality altering the anatomy/function of the nose or nasopharynx, a clinically significant history of epistaxis within the last 3 months, nasal/sinus surgery within 6 months of Day 0, including nasopharyngeal malignancy, arterio-venous malformation, or undiagnosed nasopharyngeal mass
• Inhaled bronchodilator/inhaled steroid use within the last 12 months before Day 0
• Acute upper respiratory tract infection in the past 6 weeks.
• Receipt of systemic glucocorticoids (in a dose ≥ 5 mg prednisone daily or equivalent) within one month, or any other cytotoxic or immunosuppressive drug within 6 months before Day 0
• Receipt of any vaccine within 30 days of Day -14
• Any significant medical condition/prescribed drug, under the PI's discretion
• Presence of cold-like symptoms and/or fever on Day -14 or Day 0.
• Receipt of blood/blood products/loss (including blood donations) of 550 mL or more of blood during the 3 months prior to Day -14.
• Significant history/presence of drug/alcohol misuse by self-report.
• Current use of drugs through nose inhalation or inhaled route including recreational drugs.
• Regular smoking and/or vaping and/or using nicotine-containing products in the past 3 months OR >5 pack-year lifetime history by self-report (5 pack years is equivalent to one pack of 20 cigarettes per day for 5 years).
• History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food/drug, as assessed by the PI.
• Clinically active rhinitis (including hay fever)/history of moderate to severe rhinitis/history of seasonal allergic rhinitis likely to be active at the time of inclusion into the study and/or requiring regular nasal corticosteroids on an at least weekly basis, within 30 days of enrolment.
• Anyone with any of the following contraindications to receiving the Fluenz Tetra Vaccine:

• Allergy to gentamicin, gelatin or the other ingredients of the fluenz vaccine.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Великобритания · 1 центр

• Imperial Clinical Research Facility, Imperial College Healthcare NHS Trust — London

Идентификаторы

NCT: NCT06620185 · 23HH8514

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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