Clinical trial NCT05983471: Efficacy and Safety of ME-015 (Suplatast Tosilate) in Cough Related to Idiopathic Pulmonary Fibrosis (COSMIC-IPF)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Cough
IPF
Fibrotic Lung Disease
Chronic Cough
Coughing
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
Lead sponsor: Melius Pharma AB
Sponsor class: INDUSTRY
First posted: 2023-08-09
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Wake time cough frequency during 24 hours
timeFrame: Change from Baseline to Day 14 in the respective treatment period
Secondary outcomes:
measure: Cough severity in the last 24 hours
timeFrame: Change from Baseline to Day 14 in the respective treatment period
measure: Cough-related quality of life in the last 24 hours
timeFrame: Change from Baseline to Day 14 in the respective treatment period
measure: Overall patient-reported health status
timeFrame: Change from Baseline to Day 14 in the respective treatment period
measure: Safety: Treatment-Emergent Adverse Events
timeFrame: From enrolment into the trial until end of follow-up, circa 50-60 days per subject
measure: Safety: Adverse Events and Serious Adverse Events
timeFrame: From enrolment into the trial until end of follow-up, circa 50-60 days per subject
measure: Safety: Vital Signs - blood pressure
timeFrame: From enrolment into the trial until end of follow-up, circa 50-60 days per subject
measure: Safety: Vital Signs - heart rate
timeFrame: From enrolment into the trial until end of follow-up, circa 50-60 days per subject
measure: Safety: Vital Signs - body temperature
timeFrame: From enrolment into the trial until end of follow-up, circa 50-60 days per subject
measure: Safety: Clinical Laboratory Results
timeFrame: From enrolment into the trial until end of follow-up, circa 50-60 days per subject
Other outcomes:
measure: Exploratory Endpoint: 24-hour Cough Frequency
timeFrame: Change from Baseline to Day 14 in the respective treatment period
measure: Exploratory Endpoint: Sleep-time Cough Frequency
timeFrame: Change from Baseline to Day 14 in the respective treatment period
measure: Exploratory Endpoint: Patient-Reported Breathlessness
timeFrame: Change from Baseline to Day 14 in the respective treatment period
measure: Exploratory Endpoint: Patient-reported Cough Hypersensitivity
timeFrame: Change from Baseline to Day 14 in the respective treatment period
measure: Exploratory Endpoint: Eosinophilia
timeFrame: Change from Baseline to Day 14 in the respective treatment period
measure: Exploratory Endpoint: Pulmonary Function
timeFrame: Change from Baseline to Day 14 in the respective treatment period
measure: Exploratory Endpoint: ME-015 Concentration in Blood
timeFrame: Change from Baseline to Day 14 in the respective treatment period
Locations:
city: Guntur
country: India
facility: Aditya Multi Specialty Hospital
state: Andhra Pradesh
city: Belgaum
country: India
facility: KLE's Dr Prabhakar Kore Hospital & Medical Research Centre
state: Karnataka
city: Pune
country: India
facility: ACE Hospital and Research Centre
state: Maharashtra
city: Coimbatore
country: India
facility: Hindusthan Hospital
state: Tamil Nadu
city: Kanpur
country: India
facility: GSVM Medical College, Murari Lal Chest Hospital
state: UP
city: Kolkata
country: India
facility: Health Point Hospital
state: West Bengal
Study officials:
References: