Lung Immune Challenge Study: Controlled Exposure to Inhaled Resiquimod (R848)

NCT06488118 | Recruiting

• 2 other identifiers: A096886MR/Y000935/1
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Respiratory viral infections can be a cause of significant illness, particularly in vulnerable individuals as 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. The investigators 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. This has been used 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.

Conditions

Innate Immunity; Mucosal Immunity; Asthma; Viral Infection

Keywords

Asthma; Immunology; Viral infection; Airway Epithelium; Respiratory Medicine; Innate Immunity; Sputum

Outcome Measures

Primary Outcomes (1)

• Change in Serum or Sputum CXCL10

  Change in CXCL10 in serum or induced sputum before and after inhaled R848

  3 weeks from screening visit until 24 hours after inhaled R848 challenge

Secondary Outcomes (7)

• Change in FEV1

  Change in FEV1 at 1, 4, 8, 24 and 48 hours after single ascending dose inhaled R848 or saline

• Change in Temperature

  Change in temperature (degrees celsius) at 1, 4, 8, 24 and 48 hours after single ascending dose inhaled R848 or saline

• Change in Pulse Rate

  Change in Pulse Rate at 1, 4, 8, 24 and 48 hours after single ascending dose inhaled R848 or saline

• Change in Systolic Blood Pressure

  Change in systolic blood pressure at 1, 4, 8, 24 and 48 hours after single ascending dose inhaled R848 or saline

• Change in Peripheral Eosinophil Counts

  Change in peripheral eosinophil counts at 4, 24 and 48 hours after single ascending dose inhaled R848 or saline

Study Arms (8)

R848 0.1 μg/mL

ACTIVE COMPARATOR

Inhaled Resiquimod (R848) 0.1 μg/mL

Drug: R848

R848 1.0 μg/mL

ACTIVE COMPARATOR

Inhaled Resiquimod (R848) 1.0 μg/mL

Drug: R848

R848 10 μg/mL

ACTIVE COMPARATOR

Inhaled Resiquimod (R848) 10 μg/mL

Drug: R848

R848 100 μg/mL

ACTIVE COMPARATOR

Inhaled Resiquimod (R848) 100 μg/mL

Drug: R848

Saline

PLACEBO COMPARATOR

Inhaled Saline

Drug: Saline

Asthma volunteers inhaled R848

ACTIVE COMPARATOR

Highest tolerated dose inhaled R848 in healthy volunteers to be given to volunteers with asthma

Drug: R848

Asthma volunteers inhaled saline

PLACEBO COMPARATOR

Inhaled saline to be given to volunteers with asthma

Drug: Saline

Sample only

NO INTERVENTION

Sample only collection from volunteers for protocol optimisation

Interventions

R848 DRUG

Inhaled R848 dose ranging from 0.1 to 100 μg/mL

Asthma volunteers inhaled R848; R848 0.1 μg/mL; R848 1.0 μg/mL; R848 10 μg/mL; R848 100 μg/mL

Saline DRUG

Inhaled Saline control

Asthma volunteers inhaled saline; Saline

Eligibility Criteria

• Age: 18 Years - 60 Years
• Gender Eligibility Details: Male (Cisgender) Female (Cisgender)
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Akhilesh Jha: lead
• University of Cambridge: collaborator

Study Sites (1)

NIHR Cambridge Clinical Research Facility

Cambridge, Cambridgeshire, CB2 0SL, United Kingdom

RECRUITING

Related Publications (2)

• Jha A, Thwaites RS, Tunstall T, Kon OM, Shattock RJ, Hansel TT, Openshaw PJM. Increased nasal mucosal interferon and CCL13 response to a TLR7/8 agonist in asthma and allergic rhinitis. J Allergy Clin Immunol. 2021 Feb;147(2):694-703.e12. doi: 10.1016/j.jaci.2020.07.012. Epub 2020 Jul 24.

  PMID: 32717253 BACKGROUND

• Progatzky F, Jha A, Wane M, Thwaites RS, Makris S, Shattock RJ, Johansson C, Openshaw PJ, Bugeon L, Hansel TT, Dallman MJ. Induction of innate cytokine responses by respiratory mucosal challenge with R848 in zebrafish, mice, and humans. J Allergy Clin Immunol. 2019 Jul;144(1):342-345.e7. doi: 10.1016/j.jaci.2019.04.003. Epub 2019 Apr 16. No abstract available.

  PMID: 31002833 BACKGROUND

Related Links

• Study website

MeSH Terms

Conditions

Asthma; Virus Diseases

Interventions

resiquimod; Sodium Chloride

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Infections

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Akhilesh Jha, MBBS; MRCP; PhD

CONTACT

+44 01223254642; cuh.lungchallenge@nhs.net

Jade Joseph, BSc; MSc

CONTACT

+44 01223254642; cuh.lungchallenge@nhs.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MRC Clinician Scientist

Study Record Dates

• First Submitted: June 28, 2024
• First Posted: July 5, 2024
• Study Start: May 24, 2024
• Primary Completion: May 1, 2025
• Study Completion: July 1, 2025
• Last Updated: July 10, 2024

Record last verified: 2024-07

Locations

GB (1)