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
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 6
- 主要终点
- Wake time cough frequency during 24 hours
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Interactive web response system (IWRS)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of IPF according to 2018 ATS/ERS/JRS/ALAT guidelines, confirmed by high-resolution computed tomography (HRCT) chest scan taken < 2 years ago
- •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 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)
- •Willing and able to comply with the protocol
- •Life expectancy > 6 months
- •Stable medical condition: stable treatment for > 12 weeks and absence of acute exacerbations for > 4 weeks
- •FVC ≥ 40% predicted
- •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
排除标准
- •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 ACE inhibitor or sitagliptin
- •Any antitussive treatment, including opioid-based and OTC, for treatment of cough within 4 weeks of Screening or at any point during the study
- •BMI < 18 kg/m2 or ≥ 40 kg/m2
- •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
- •Condition that could affect drug absorption
- •Recent history of stroke or TIA
- •Resting blood pressure > 160/90 mmHg
- •Pregnant/lactating women
- •Investigational drug or biologic within the last 2 months
- •Blood donation within the last 56 days or plasma donation within the last 7 days
- •Severe medical/ psychiatric condition posing risk to trial participation
研究组 & 干预措施
Treatment Arm 1
2 weeks of blinded active treatment, followed by 2 weeks of blinded placebo treatment (wash-out), followed by 2 weeks of blinded placebo treatment, followed by 1 week of follow-up with neither active nor placebo treatment
干预措施: ME-015 (Suplatast Tosilate) (Drug)
Treatment Arm 1
2 weeks of blinded active treatment, followed by 2 weeks of blinded placebo treatment (wash-out), followed by 2 weeks of blinded placebo treatment, followed by 1 week of follow-up with neither active nor placebo treatment
干预措施: Identical placebo (Other)
Treatment Arm 2
2 weeks of blinded placebo treatment, followed by 2 weeks of blinded placebo treatment (wash-out), followed by 2 weeks of blinded active treatment, followed by 1 week of follow-up with neither active nor placebo treatment
干预措施: ME-015 (Suplatast Tosilate) (Drug)
Treatment Arm 2
2 weeks of blinded placebo treatment, followed by 2 weeks of blinded placebo treatment (wash-out), followed by 2 weeks of blinded active treatment, followed by 1 week of follow-up with neither active nor placebo treatment
干预措施: Identical placebo (Other)
结局指标
主要结局
Wake time cough frequency during 24 hours
时间窗: 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
次要结局
- Cough severity in the last 24 hours(Change from Baseline to Day 14 in the respective treatment period)
- Cough-related quality of life in the last 24 hours(Change from Baseline to Day 14 in the respective treatment period)
- Overall patient-reported health status(Change from Baseline to Day 14 in the respective treatment period)
- Safety: Treatment-Emergent Adverse Events(From enrolment into the trial until end of follow-up, circa 50-60 days per subject)
- Safety: Adverse Events and Serious Adverse Events(From enrolment into the trial until end of follow-up, circa 50-60 days per subject)
- Safety: Vital Signs - blood pressure(From enrolment into the trial until end of follow-up, circa 50-60 days per subject)
- Safety: Vital Signs - heart rate(From enrolment into the trial until end of follow-up, circa 50-60 days per subject)
- Safety: Vital Signs - body temperature(From enrolment into the trial until end of follow-up, circa 50-60 days per subject)
- Safety: Clinical Laboratory Results(From enrolment into the trial until end of follow-up, circa 50-60 days per subject)