Short summary

This study will investigate whether the drug called senicapoc can prevent worsening of the scarring in interstitial lung disease. Researchers will compare senicapoc to a placebo to see if senicapoc works to prevent lung function worsening Participants will be asked to take 3 tablets a day for a period of 26 weeks. Within this period doctors will follow the participants, ask for experience of adverse events and check lung function. A total of 4 visits is required.

Rationale

Fibrosing interstitial lung disease (F-ILD) represents a heterogeneous group of chronic, severely debilitating, and ultimately lethal lung diseases with limited treatment options. The common denominator for F-ILD is similarities regarding development of scarring of the lungs. Two antifibrotic treatments (pirfenidone, nintedanib), have shown to improve progression free survival, and slowed the decline in forced ventilatory capacity (FVC). These treatments are currently approved in the European Union and are standard of care for many patients. But both treatments have a lot of unbeneficial side-effects, making it unbearable for many patients to receive full dose treatment and often patients progress despite antifibrotic treatment. Senicapoc is a selective and highly potent inhibitor of KCa3.1 channels. The KCa3.1 channel is pivotal in Ca+ signaling and plays a central role in fibroblast processes. It is therefore thought to play an important role in the development of many fibrotic diseases, including lung fibrosis. Two lines of evidence using human lung cells and lung slices indicate that blocking of the KCa3.1 channel attenuates many profibrotic activities and support the expected antifibrotic effect of senicapoc. In sheep studies, senicapoc has shown not only to attenuate disease progression but also signs of reversing the disease. It has been extensively tested in animal studies and shown no toxic or unbeneficial effects, and it has been tested in human studies in healthy volunteers, patients with sickle cell disease, asthma, and COVID-19, without revealing any serious adverse reactions. Aims, Objectives and hypothesis: The aim of this study is to investigate the effect of senicapoc in preventing progression in F-ILD. Evaluation will consist of spirometry, 6-minute walking distance test and diffusion capacity. Sidewise changes in quality of life and degree of dyspnea will be obtained. Clinical examinations and bloodtests will be done to evaluate a second aim of this study; the safety of senicapoc in IPF patients.

Description of the cohort

Paticipants diagnosed with fibrotic interstitial lung disease, regardless of the sub diagnosis, within 5 years. the participants will be recruted from tertiary care centers, in Denmark, Estonia and England.

Data and biological material

Blood samples, questionnaire data and data from patient journals (demografic, diagnosis, comorbidities, medication).

Collaborating researchers and departments

Department of Respiratory Diseases and Allergy, Aarhus University Hospital

• Elisabeth Bendstrup, Professor

Department of Respiratory Diseases, Odense University Hospital

• Jesper Davidsen, Professor

Department of Respiratory Diseases, Gentofte Hospital

• Saher Shaker, Ass professor

Department of Pulmonology, University of Tartu

• Alan Altraja, Professor

Dept of Respiratory Sciences, University of Leicester Clinical Sciences

• Peter Bradding, Professor

Respiratory Medicine, University of East Anglia

• Andrew Wilson