Efficacy and Safety of ME-015 (Suplatast Tosilate) in Cough Related to Idiopathic Pulmonary Fibrosis (COSMIC-IPF)

Study Overview
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Brief Summary
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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 very 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 July 2023, there is no approved treatment for the indication of IPF-cough. There is an enormous unmet clinical need for an effective, safe and well-tolerated oral treatment. The COSMIC-IPF Phase 2 trial is the first clinical trial assessing ME-015 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
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This double-blind, 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. 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 wake time cough frequency measured objectively with the VitaloJak device over a 24-hour period. VitaloJak recordings are analysed using a blinded, independent, central review process. The study is conducted as a single-country, multi-site clinical trial in India with Melius Pharma AB as the Sponsor.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Cross-over Trial to Evaluate the Efficacy and Safety of ME-015 (Suplatast Tosilate) in Cough Related to Idiopathic Pulmonary Fibrosis

Conditions
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Idiopathic Pulmonary Fibrosis, Cough

Intervention / Treatment
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* Drug: ME-015 (Suplatast Tosilate)
* Other: Identical placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of idiopathic pulmonary fibrosis (IPF) according to the 2018 American Thoracic Society (ATS) guidelines, confirmed by high-resolution computed tomography (HRCT) chest scan taken within < 2 years Age ≥ 18 years Cough attributed to IPF unresponsive to standard anti-tussive treatment and present for > 8 weeks Arithmetic mean of ≥ 10 coughs/hour during waking hours Ability to read, comprehend, and complete the informed consent form (ICF) and all questionnaires in the study without help Cough severity score of ≥ 40 mm on a 0-to-100 mm Visual Analogue Scale (VAS) Life expectancy > 6 months Stable medical condition: stable treatment for > 12 weeks and absence of acute exacerbations for > 4 weeks Antifibrotics pirfenidone and nintedanib are allowed if the patient has been on a stable dose for ≥ 12 weeks and remains on a stable dose throughout the study Forced vital capacity (FVC) ≥ 40% predicted Ratio between forced expiratory volume in one second and forced vital capacity (FEV1 / FVC) ≥ 65% Women of childbearing potential must agree to use a highly effective method of contraception 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: Likely need for lung transplantation in next 12 months Permanent long-term oxygen therapy Use of high-dose corticosteroids or cytotoxic medications History of unstable or deteriorating cardiac or pulmonary disease in the preceding 6 months Current smoking, vaping, or tobacco chewing Treatment with an angiotensin-converting enzyme (ACE) inhibitor or sitagliptin started in the last 12 weeks Suspected acute infection, including COVID-19 or influenza or any upper respiratory tract infection History of malignancy within the last 2 years History of drug/alcohol dependency/abuse within the last 2 years Recent history of stroke or transient ischemic attack Blood pressure > 160/90 mmHg Pregnant/lactating women Exposure to an investigational drug or biologic within the last 2 months Blood donation within the last 56 days or plasma donation within the last 7 days Body Mass Index < 18 kg/m2 or ≥ 40 kg/m2

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ME-015 (Suplatast Tosilate)<br>ME-015 (Suplatast Tosilate) 2 x 100 mg capsule t.i.d. (three times per day), for 2 weeks | Drug: ME-015 (Suplatast Tosilate)<br>* Oral capsule form, 200 mg t.i.d. (total 600 mg per 24 hours)<br>* Other names: Suplatast Tosilate;|
| Placebo Comparator: Placebo<br>Identical placebo capsules 2 x t.i.d. (three times per day), for 2 weeks | Other: Identical placebo<br>* Without active component<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wake time cough frequency during 24 hours | Measured objectively with the cough recording device VitaloJak with centralized, blinded, independent analysis | Change from Baseline to Day 14 in the respective treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cough severity in the last 24 hours | Visual Analogue Scale (VAS) ranging from 0 - 100 mm where higher values indicate more severe cough | Change from Baseline to Day 14 in the respective treatment period | 
| Cough-related quality of life in the last 24 hours | Leicester Cough Questionnaire (LCQ) total score ranging from 3 - 23 where lower values indicate greater impairment of health status due to cough | Change from Baseline to Day 14 in the respective treatment period | 
| Overall patient-reported health status | 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 | Change from Baseline to Day 14 in the respective treatment period | 
| Safety: Treatment-Emergent Adverse Events | Number of patients in each treatment period (active or placebo) who experience a treatment-emergent adverse event (TEAE) | Number of TEAEs from Baseline to Day 14 in the respective treatment period | 
| Safety: Serious Adverse Events | Number of patients in each treatment period (active or placebo) who experience a serious adverse event (SAE) | Number of SAEs from Baseline to Day 14 in the respective treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IPF-cough, IPF cough, Idiopathic Pulmonary Fibrosis, Chronic cough, Suplatast, Melius, Refractory cough