In Vitro Evaluation of a Novel Drug on Airway Epithelial Cells Obtained From Participants With Severe Asthma

NCT02740049 | Completed Early Phase 1 Results

• 1 other identifier: 15IC2844
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Asthma is a long term disease of the lungs. In asthma patients the sensitive airway tubes narrow in reaction to something that irritates the airways such as allergens or environmental pollutants. There is currently no cure for asthma and new medicines or combinations of medicines are needed that will be of benefit to patients particularly those with a more severe disease. Activation of certain signal molecules inside the lung cells may participate in the development of asthma and the response to allergens. Blocking these signal molecules specifically with medicines might therefore be beneficial in the treatment of asthma. In this study we want to test a new medicine that specifically targets a subset of signal molecules that are associated with the allergen response in the lung. In particular, we want to test this medicine on cells obtained from the lungs of asthma patients. Understanding the effects of this new medicine on these asthmatic lung cells will give vital information on how this new medicine works before we can test it in asthma patients.

Conditions

Asthma

Keywords

Epithelial Cells

Outcome Measures

Primary Outcomes (3)

• Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.

  Measurement of cytokine levels in cell supernatant after stimulation of isolated epithelial cells. For this study epithelial cells from severe asthma patients (n = 9) were cultured and stimulated with either IFN/TNF or IL-13 to induce inflammation. Cells are then treated with VR588 (2 concentration) or with Fluticasone Propionate (FP) or with CP690553 (CP; Tofacitinib). The concentrations of drugs are listed in the title (e.g. 10-9M).

  21 days

• Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.

  Measurement of cell viability after stimulation of isolated epithelial cells. For this study epithelial cells from severe asthma patients (n = 9) were cultured and stimulated with either IFN/TNF or IL-13 to induce inflammation. Cells are then treated with VR588 (2 concentration) or with Fluticasone Propionate (FP) or with CP690553 (CP; Tofacitinib). The concentrations of drugs are listed in the title (e.g. 10-9M).

  21 days

• Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.

  Measurement of activation of phospho-STAT1 member of the JAK/STAT signaltransduction pathway in cell lysates. For this study epithelial cells from severe asthma patients (n = 9) were cultured and stimulated with either IFN/TNF or IL-13 to induce inflammation. Cells are then treated with VR588 (2 concentration) or with Fluticasone Propionate (FP) or with CP690553 (CP; Tofacitinib). The concentrations of drugs are listed in the title (e.g. 10-9M).

  21 days

Study Arms (1)

Astma patients

EXPERIMENTAL

Participant undergoes a bronchoscopy to isolate epithelial cells

Drug: VR588

Interventions

VR588 DRUG

Evaluation of the efficacy of a novel JAK/STAT inhibitor, VR588, in isolated epithelial cells from asthma patients

Astma patients

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must be able to give informed consent.
• The definition of severe asthma will be on the basis of:
• Treatment: High dose of ICS ± OCS ≥ 1000mcg FP daily or equivalent plus one other controller medication.
• Disease Control: Uncontrolled (GINA guidelines), three or more of the following present in any week in the preceding 4 weeks:
• Daytime symptoms more than twice per week
• Any limitation of activities
• Nocturnal symptoms once or more per week
• Need for reliever treatment more than twice per week
• Prebronchodilator FEV1 \<80% predicted or personal best AND/OR Frequent severe exacerbations (≥2 per year requiring high dose OCS or doubling of maintenance dose for at least three days or requiring hospitalisation).
• Asthma Diagnosis:
• Improvement in FEV1 ≥ 12% or 200ml predicted after inhalation of 400mcg salbutamol OR Diurnal variation in PEF: amplitude % mean of twice daily PEF \> 8% OR Decrease in FEV1 ≥ 12% and \>200ml within 4 weeks after tapering treatment with one or more of the following drugs: ICS, OCS, LABA, SABA PLUS A history of wheeze occurring spontaneously or on exertion.

You may not qualify if:

• Patients with a FEV1 \< 1L
• Any other active lung condition
• Subjects unable to give consent

Sponsors & Collaborators

• Imperial College London: lead
• Vectura Limited: collaborator

Study Sites (1)

Royal Brompton & Harefield NHS Foundation Trust

London, SW3 6NP, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr Coen Wiegman
• Organization: Imperial College London

c.wiegman@imperial.ac.uk

+44(0)2075947846

Study Officials

• Fan Chung, MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2016
• First Posted: April 15, 2016
• Study Start: January 27, 2016
• Primary Completion: October 19, 2016
• Study Completion: October 19, 2016
• Last Updated: October 28, 2019
• Results First Posted: October 9, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)