A Phase 2 Study to Evaluate Dose-Response of TAS-115 in Patients with Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype

JRCT ID: jRCT2051210050

Registered date:12/07/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype
• Date of first enrollment: 26/10/2021
• Target sample size: 240
• Study type: Interventional

Intervention(s)

Investigational Product, Dosage, and Mode of Administration:
TAS-115 (Dose 1 or Dose 2, or placebo) will be administered orally once daily to patients in the fasted state at bedtime. Study treatment will be repeated for 5 consecutive days followed by a 2-day rest period (5-day on and 2-day off schedule)
Reference and/or Control Therapy, Dosage, and Mode of Administration:
- Patients treated with nintedanib previously
Nintedanib (active or placebo) will be orally administered to patients twice daily after meals.
- Patients treated with pirfenidone previously
Pirfenidone (active or placebo) will be administered orally three times daily after meals.

Outcome(s)

• Primary Outcome: 26-week rate of decline in FVC
• Secondary Outcome: 52-week rate of decline in FVC, Endpoints related to FVC, DLco, SpO2, SGRQ, Time to first acute exacerbation, Time to first respiratory-related hospitalization, Overall survival, Time to first acute exacerbation or death, Adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1)Provide written informed consent
(2)Patients whose age at the time of informed consent is >= 20 years
(3)Patients who have been given a diagnosis of interstitial lung disease by the investigator and have received nintedanib or pirfenidone for at least 90 days at Visit 1 for any of the approved indications
(4)Pulmonary fibrosis of > 10% of all lung fields observed from central reading of chest high-resolution computed tomography (HRCT) at Visit 1
(5)Patients who meet the following criteria for progressiveness:
Decline in percent predicted forced vital capacity (%FVC) based on a relative decline of >= 5%/year at Visit 1, as follows
(Basepoint %FVC - Visit 1 %FVC) / Basepoint %FVC x 365 (days) / Measurement interval (days) x 100 >= 5%

However, if the measurement interval is less than 365 days for decline in %FVC, a relative decline of >= 5% is required as follows:
(Basepoint %FVC - Visit 1 %FVC) / Basepoint %FVC x 100 >= 5%

The basepoint data are defined as measured data of the earliest date among the previous data obtained immediately before the start of or during the treatment with antifibrotic drugs (nintedanib or pirfenidone) that have been administered at Visit 1, excluding those with a clear reason such as incorrect measurement. The interval between the measurement date of basepoint data and the measurement at Visit 1 should be at least 90 days apart.

(6)Difference between the FVC at Visit 2 and the FVC at Visit 1 of =< +5% or =< 150 mL, as calculated below:
(FVC at Visit 2- FVC at Visit 1) / FVC at Visit 1 x 100 =< 5%
Or FVC at Visit 2 - FVC =< 150 mL at Visit 1

(7)Patients with a %FVC: >= 50% at Visit 2
(8)Percent predicted diffusing capacity for carbon monoxide (%DLco) [corrected for the hemoglobin (Hb) level at Visit 1] of >= 25%
(9)Patients who have not started or discontinued treatment other than nintedanib or pirfenidone for interstitial lung disease within 42 days before randomization
(10)The extent of fibrotic changes is greater than the extent of emphysema on chest HRCT scan at Visit 1 (the central review will be performed, but the final decision will be made by the investigator).
(11)Patients who can take medication orally

Exclude criteria

(1)Patients with a history of TAS-115 use
(2)Patients who received the following treatment during the specified period before randomization in this study
a)Major surgery within 28 days before randomization (surgical wounds have to be healed before randomization)
b)Patients who received nintedanib or pirfenidone within 7 days before randomization
c)Treatment with another investigational product within 5 half-lives prior to randomization in this study (if half-life is unknown, 56 days must have elapsed)
(3)Patients with airflow obstruction (percent forced expiratory volume in 1 second [FEV1/FVC] before treatment with a bronchodilator is < 0.7 at Visit 2)
(4)Patients given a diagnosis of severe pulmonary hypertension
(5)Patients with medical history of acute exacerbation of interstitial lung disease
(6)Patients with a history of hypersensitivity to any component of TAS-115
(7)Patients with moderate or severe adverse drug reactions to prior treatment for moderate or severe decreased appetite, malaise, diarrhoea, nausea, skin disorder or interstitial lung disease (excluding alopecia and pigmentation)
(8)Pregnant or lactating women
(9)Male patients or female patients of childbearing potential who do not agree to use appropriate contraception during the following period:
Male patients: During the study and for 4 months after the last dose of study drug
Female patients of childbearing potential: During the study and for 7 months after the last dose of study drug

Related Information

• Primary Sponsor: Motoo Yoshiharu