Lung Immune Challenge Study Controlled Exposure to Inhaled Resiquimod (R848) to Study Mechanisms of Inflammation

A096886

Respiratory viral infections can be a cause of significant illness, particularly in vulnerable individuals as we have seen in the COVID-19 pandemic. An underactive or overactive immune response can lead to ineffective resolution of inflammation after an infection, especially in people with airway diseases such as asthma. A better understanding of immune responses to infection that does not rely on cell or animal models is crucial to help develop better treatments for lung inflammation. An established method of studying inflammation in humans is through careful and controlled exposure (or "challenge") with a mimic of a virus to simulate an infection in a similar manner to that of a virus, but with the advantage of not causing an infection. We have already developed a well-tolerated mimic of human viral infection using a sterile substance called Resiquimod (or R848). Since it does not contain living organisms there is no possibility of being infected. We have used this previously as a nasal spray to cause a mild short-lived inflammation that mimics a mild cold. This has been used safely in a range of people of different ages including those who have asthma. There are differences however in how the nose and lungs respond to viral infections. This is particularly true in those with airway diseases such as asthma, who have cells in the airways of their lungs that respond in a different way to inflammatory triggers (such as viruses). The current study aims to build on previous research by developing a new approach of studying inflammation in the lungs using a small volume of Resiquimod. This will be done by gently inhaling a fine mist through a mouthpiece into the lungs. Blood and phlegm samples would then be collected to assess inflammation and how well people tolerate the procedure.

2024-05-24

2025-05-01

2025-07-01

Recruiting

36

Inclusion Criteria: * Male or female aged between 18 and 60 years. * Willing and able to give informed consent for participation in the study. * Female participants of child-bearing potential and male participants whose partner is of child-bearing potential must be willing to ensure that they or their partner use effective contraception during the study. * Clinically acceptable laboratory measurements and ECG at enrolment. * Ability to expectorate sputum. * Optional additional swab for SARS-CoV-2 testing will be collected from participants if required by local or/and national health and safety policies at the time of sampling. For healthy volunteers: * No clinical history of asthma * Normal baseline spirometry i.e. FEV1/Forced Vital Capacity (FVC) ratio z-score greater than the lower limit of normal. For volunteers with asthma: * Physician-diagnosed mild to moderate asthma which is not poorly controlled as evidenced by an Asthma Control Questionnaire (ACQ-5) score of ≤1.5. * They are permitted to be on inhaled corticosteroids (ICS), long-acting beta agonist (LABA) and long-acting muscarinic antagonists (LAMA). * Pre-bronchodilator FEV1 ≥70% predicted. * Evidence of bronchial hyperreactivity as evidenced by either (i) Bronchodilator reversibility (increase FEV1 ≥12% and 200 mL); (ii) Positive methacholine challenge (PC20 \< 8mg/ml), or (iii) Positive challenge test as per current CUH policy. Exclusion Criteria: * Upper respiratory tract infection in preceding 14 days. * Lower respiratory tract infection in preceding 28 days. * Female participants who are pregnant, lactating or planning pregnancy. * Respiratory diseases (other than asthma where specified). * Significant extrapulmonary medical conditions. * Extreme obesity (BMI \>40). * Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study. * Participants who have participated in another research study involving an investigational product in the past 12 weeks. * No newly prescribed courses of medication including corticosteroids in the four weeks before first study dose other than mild analgesia, vitamins, and supplements. * Smoking tobacco or vaping products in previous 6 months. * Smoking history of \>5 pack years.

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT']}}, 'enrollmentInfo': {'count': 36, 'type': 'ESTIMATED'}}

2024-07-04