Idiopathic Pulmonary Fibrosis, Cough, IPF, Fibrotic Lung Disease, Chronic Cough, Coughing
Conditions
Keywords
IPF-cough, IPF cough, Idiopathic Pulmonary Fibrosis, Chronic cough, Suplatast, Melius, Refractory cough, IPF, Fibrotic cough, Melius Pharma, RCT, Sequential, Cough frequency, Cough severity, India, fibrosis, Oral, New Chemical Entity, Small molecule, Nowak, Kornfeld, Sweden
Brief summary
Orally administered ME-015 (Suplatast Tosilate) has been available on the market as a prescription drug for allergy-related conditions in Japan since 1995 with a good safety and tolerability profile. There is preclinical and exploratory clinical evidence suggesting that ME-015 may be effective in treating cough caused by idiopathic pulmonary fibrosis (IPF cough). 80% of patients with idiopathic pulmonary fibrosis (IPF) are affected by a devastating dry cough that is often not responsive to standard cough treatments and causes significant psychological and physiological suffering as well as reduced quality of life. As of November 2024, there is no approved treatment for IPF cough. There is an enormous unmet clinical need for an effective, safe and well-tolerated oral treatment; particularly as approved antifibrotic treatments (pirfenidone and nintedanib) have not been shown to reduce cough in controlled clinical trials. The COSMIC-IPF Phase 2a trial is the first clinical trial assessing ME-015 (an NCE outside of Japan) for the treatment of IPF cough and aims to generate clinical proof-of-concept results regarding the safety and efficacy of ME-015 in this condition.
Detailed description
This quadruple blinded, cross-over, placebo-controlled clinical trial will randomize patients with stable idiopathic pulmonary fibrosis (IPF) and cough related to IPF (IPF cough) in a 1:1 fashion to one of two treatment sequences: active treatment followed by placebo, or placebo followed by active treatment. Each 14-day active/placebo treatment phase is preceded by a wash out period. The treatment sequences are followed by an observational 7-day follow-up period without medication. All subjects in the trial receive standard-of-care antifibrotic treatment for IPF. There is a single-blinded placebo run-in period before randomization to create a stable baseline and adjust for the anticipated placebo effect at study entry. Treatment assignment is blinded to patients, investigators, site personnel, data analysts and Sponsor. The active treatment is ME-015 (Suplatast Tosilate) 200 mg t.i.d. (three times per day) administered as oral capsules. The placebo treatment consists of identical capsules without the active component. The primary efficacy endpoint is the effect on awake time cough frequency measured objectively with the VitaloJak device over a 24-hour period. VitaloJak recordings are analysed using a blinded, independent, central review and validation process. The study is conducted as a single-country, multi-centre clinical trial in India with Melius Pharma AB as the Sponsor. External central adjudication of HRCT images by a UK-based KOL ensures guideline-based diagnoses of IPF. Treatment needs to follow international guideline-based standard of care for IPF, and all Indian sites have been chosen to reflect a similar standard of care as practiced in Europe and the U.S. Only literate patients are enrolled into the trial and all patient-facing material is made available in English and all common local languages.
Interventions
DRUGME-015 (Suplatast Tosilate)
Oral capsule form, 200 mg t.i.d. (total 600 mg per 24 hours)
OTHERIdentical placebo
Without active component
Sponsors
Melius Pharma AB
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Interactive web response system (IWRS)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of IPF according to 2018 ATS/ERS/JRS/ALAT guidelines, confirmed by high-resolution computed tomography (HRCT) chest scan taken \< 2 years ago 2. Age ≥ 18 years 3. Cough attributed to IPF unresponsive to standard anti-tussive treatment and present for \> 8 weeks 4. Arithmetic mean of ≥ 10 coughs/hour during waking hours 5. Ability to read, comprehend, and complete the ICF and all questionnaires in the study without help 6. Cough severity score of ≥ 40 mm on a 0-to-100 mm Visual Analogue Scale (VAS) 7. Willing and able to comply with the protocol 8. Life expectancy \> 6 months 9. Stable medical condition: stable treatment for \> 12 weeks and absence of acute exacerbations for \> 4 weeks 10. FVC ≥ 40% predicted 11. FEV1 / FVC ≥ 65% 12. Women of childbearing potential must agree to use a highly effective method of contraception 13. Male partner must agree to use a condom during the study, unless they had a vasectomy \> 6 months prior to first study drug administration
Exclusion criteria
1. Likely need for lung transplantation in next 12 months 2. Permanent long-term oxygen therapy 3. Use of high-dose corticosteroids or cytotoxic medications 4. History of unstable or deteriorating cardiac or pulmonary disease in the preceding 6 months 5. Current smoking, vaping, or tobacco chewing 6. Treatment with an ACE inhibitor or sitagliptin 7. Any antitussive treatment, including opioid-based and OTC, for treatment of cough within 4 weeks of Screening or at any point during the study 8. BMI \< 18 kg/m2 or ≥ 40 kg/m2 9. Suspected acute infection, including COVID-19 or influenza or any upper respiratory tract infection 10. History of malignancy within the last 2 years 11. History of drug/ alcohol dependency/ abuse within the last 2 years 12. Condition that could affect drug absorption 13. Recent history of stroke or TIA 14. Resting blood pressure \> 160/90 mmHg 15. Pregnant/lactating women 16. Investigational drug or biologic within the last 2 months 17. Blood donation within the last 56 days or plasma donation within the last 7 days 18. Severe medical/ psychiatric condition posing risk to trial participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Wake time cough frequency during 24 hours | Change from Baseline to Day 14 in the respective treatment period | Measured objectively over a 24-hour period with the cough recording device VitaloJak and processed using centralized, blinded, QC'd analysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cough-related quality of life in the last 24 hours | Change from Baseline to Day 14 in the respective treatment period | Leicester Cough Questionnaire (LCQ) total score ranging from 3 - 23 where lower values indicate greater impairment of health status due to cough |
| Overall patient-reported health status | Change from Baseline to Day 14 in the respective treatment period | Global Rating of Change Scale of cough severity (range -7 to +7) and cough frequency (range -7 to +7) where 0 indicates no change, higher values above 0 indicate larger improvement, and lower values below 0 indicate increased declined |
| Safety: Treatment-Emergent Adverse Events | From enrolment into the trial until end of follow-up, circa 50-60 days per subject | Incidence of treatment-emergent adverse events (TEAE) |
| Safety: Adverse Events and Serious Adverse Events | From enrolment into the trial until end of follow-up, circa 50-60 days per subject | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| Safety: Vital Signs - blood pressure | From enrolment into the trial until end of follow-up, circa 50-60 days per subject | Resting blood pressure (mmHg), assessed weekly |
| Safety: Vital Signs - heart rate | From enrolment into the trial until end of follow-up, circa 50-60 days per subject | Heart rate (bpm) - assessed weekly during the trial |
| Safety: Vital Signs - body temperature | From enrolment into the trial until end of follow-up, circa 50-60 days per subject | Body temperature (degrees Celsius) - assessed weekly during the trial |
| Safety: Clinical Laboratory Results | From enrolment into the trial until end of follow-up, circa 50-60 days per subject | Clinical laboratory results (chemistry, hematology, urine dipstick) analysed by a central laboratory |
| Cough severity in the last 24 hours | Change from Baseline to Day 14 in the respective treatment period | Visual Analogue Scale (VAS) ranging from 0 - 100 mm where higher values indicate more severe cough |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Endpoint: 24-hour Cough Frequency | Change from Baseline to Day 14 in the respective treatment period | 24-hr cough frequency recording with the VitaloJak device and analysed using central, blinded review and QC |
| Exploratory Endpoint: Sleep-time Cough Frequency | Change from Baseline to Day 14 in the respective treatment period | Sleep-time cough frequency based on 24-hour recording with the VitaloJak device and analysed using central, blinded review and QC |
| Exploratory Endpoint: Eosinophilia | Change from Baseline to Day 14 in the respective treatment period | Eosinophil count (total and % of white blood cells in peripheral blood) measured using a central laboratory |
| Exploratory Endpoint: Pulmonary Function | Change from Baseline to Day 14 in the respective treatment period | Pulmonary function assessed using local spirometry assessments; specifically forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and ratio of FEV1/FVC |
| Exploratory Endpoint: ME-015 Concentration in Blood | Change from Baseline to Day 14 in the respective treatment period | Concentration of ME-015 and its major metabolie M-1 is peripheral blood samples taken once at each visit alongside safety lab samples |
| Exploratory Endpoint: Patient-reported Cough Hypersensitivity | Change from Baseline to Day 14 in the respective treatment period | Patient-reported outcome assessed using the Cough Hypersensitivity Questionnaire (CHQ) |
| Exploratory Endpoint: Patient-Reported Breathlessness | Change from Baseline to Day 14 in the respective treatment period | Patient-reported outcome breathlessness assessed using the 12-item Dyspnoea-12 Questionnaire |
Countries
India
Outcome results
None listed