Senicapoc treatment for worsening fibrotic interstitial lung disease

Senicapoc in Patients With Progressive Fibrotic ILD (Interstitial Lung Disease) and IPF (Idiopathic Pulmonary Fibrosis) to Prevent Progression.

This trial will test whether senicapoc can slow or stop worsening lung scarring in adults with progressive fibrotic interstitial lung disease, including idiopathic pulmonary fibrosis.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vejle Hospital (Academic / other)
• Drugs / interventions: imatinib, methotrexate, cyclophosphamide, prednisone
• Locations: 5 sites (Aarhus N and 4 other locations)
• Trial ID: NCT06714123 on ClinicalTrials.gov

What this trial studies

Adults with progressive fibrotic ILD or progressive IPF will receive either senicapoc or a matching placebo and take three tablets daily for 26 weeks, with follow-up out to 52 weeks. Doctors will monitor lung function, record adverse events, and collect quality-of-life questionnaires across five clinic visits (baseline, week 4, 13, 26 and 52). Eligibility requires prior HRCT, documented recent FVC decline, and the ability to complete a 6-minute walk test and questionnaires. The trial builds on preclinical and animal data suggesting KCa3.1 inhibition may reduce fibrosis and uses placebo control to determine whether those signals translate to patients.

Who should consider this trial

Good fit: Adults (over 18) with progressive fibrotic interstitial lung disease or progressive IPF, recent HRCT, an FVC above 45%, documented FVC decline of ≥5% over the prior 6–24 months, and ability to walk at least 150 meters on the 6MWT are the intended participants.

Not a fit: Patients with very advanced lung impairment (for example FVC at or below study cutoffs), predominant emphysema over fibrosis on HRCT, inability to take oral medication, or inability to attend clinic visits are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, senicapoc could slow or halt progression of lung scarring, helping preserve lung function and quality of life for people with progressive fibrotic ILD.

How similar studies have performed: Existing antifibrotic drugs (pirfenidone, nintedanib) have shown benefit in slowing progression, while senicapoc is a novel KCa3.1 blocker with promising preclinical and animal data and limited prior human safety testing but little clinical efficacy data in lung fibrosis so far.

Eligibility criteria

Inclusion Criteria:

* Progressive fibrotic ILD or Progressive IPF diagnosed according to ATS/ERS/JRS/ALAT guidelines at the time of diagnosis
* Age \> 18 years
* HRCT historically performed within 24 months
* FVC \> 45 %, FEV1/FVC \> 0,7 or above LLN
* Annual FVC decline of at least 5% predicted, based on at least three FVC measurements within 6-24 months before enrolment
* Subject able to give informed consent.
* The extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan
* Male subjects of reproductive potential agree to use highly effective contraception/preventive exposure measures from the time of first dose of IMP during the study, and until 90 days (male) after the last dose of IMP.
* Female subjects agree to use highly effective contraceptive during the study, and must show a negative pregnancy test before inclution.
* Able to walk at least 150 meters during the 6MWT at screening Visit 1;
* Able to read and complete the EQ-5D, SGRQ-I, K-BILD questionnaire.

Exclusion Criteria:

* Sickle cell disease
* Any clinical condition or other condition or circumstance that, in the opinion of the investigator, may make a subject unsuitable for inclusion or unlikely or unable to complete the study or comply with study procedures and requirements.
* Known hypersensitivity to any of the IMP ingredients or a history of a significant allergic reaction to any drug as determined by the investigator
* A current immunosuppressive condition
* Clinically significant abnormalities detected on ECG of either rhythm or conduction,
* Moderate to severe hepatic impairment (Child-Pugh B or C); and/or abnormal LFT at screening,
* Clinical laboratory test suggestive of cholestasis with total serum bile acid levels \> 3xULN.
* Abnormal renal function, defined as eGFT \> 30 ml/kg
* History of malignancy within the past 5 years
* Previous participation in a clinical study with IMP for fibrotic disease within the last 6 months.
* Concurrent participation in another interventional drug, device, or biological investigational research study, or use of an investigational agent within 5 half-lives of the agent
* Lower respiratory tract infection requiring treatment within 4 weeks prior to screening and/or during the screening period.
* History of lung volume reduction surgery or lung transplant.
* Diagnosis of severe pulmonary hypertension
* Unstable cardiovascular, pulmonary (other than IPF), or other disease within 6 months prior to screening or during the screening period
* Use of any of the following therapies within 4 weeks prior to screening and during the screening period, or planned during the study: warfarin, imatinib, ambrisentan, azathioprine, cyclophosphamide, cyclosporine A, bosentan, methotrexate, sildenafil (except for occasional use), prednisone at steady dose \> 10 mg/day or equivalent.
* Current alcohol or substance abuse in the opinion of the investigator.

Where this trial is running

Aarhus N and 4 other locations

• Aarhus University Hospital — Aarhus N, Denmark (Recruiting)
• Kardiologisk Forskningsenhed 2161, Rigshospitalet — Copenhagen, Denmark (Recruiting)
• Tartu University Hospital, — Tartu, Estonia (Recruiting)
• Division of Respiratory Sciences, Glenfield Hospital — Leicester, United Kingdom (Not_yet_recruiting)
• University of East Anglia — Norwich, United Kingdom (Not_yet_recruiting)

Study contacts

• Study coordinator: Line Kølner-Augustson, MD.

Conditions Pulmonary Fibrosis, Interstitial Lung Disease; Idiopathic Pulmonary Fibrosis; pulmonary fibrosis; Senicapoc; interstitial lung disease