進行性フェノタイプを示す慢性線維化性間質性肺疾患患者を対象に,TAS-115 投与量1群,投与量2群,対照群の26週までの努力肺活量(FVC)減量率について,用量反応性を検討する. | |||
2 | |||
2021年09月10日 | |||
2021年10月26日 | |||
2021年09月01日 | |||
2024年06月30日 | |||
|
240 | ||
|
介入研究 | Interventional | |
Study Design |
|
無作為化比較 | randomized controlled trial |
|
二重盲検 | double blind | |
|
実薬(治療)対照 | active control | |
|
並行群間比較 | parallel assignment | |
|
治療 | treatment purpose | |
|
あり | ||
|
あり | ||
|
あり | ||
|
あり | ||
|
なし | none | |
|
|
(1) 文書で同意が得られている (2) 同意取得時の年齢が20歳以上である (3) 治験担当医師により間質性肺疾患と診断され,承認されたすべての適応症のいずれかに対してニンテダニブ又はピルフェニドンがVisit 1時点で90日以上投与された患者 (4) Visit 1の胸部高分解能コンピュータ断層撮影(HRCT)画像の中央判定により,肺の線維化が肺全野の10%超にみられる (5) 以下の進行性の基準を満たす患者 Visit 1に以下のとおり相対値で5%/年以上の努力肺活量予測値に対する割合(%FVC)の低下が認められた患者 (基点の%FVC - Visit 1の%FVC)/基点の%FVC×365(日)/測定間隔(日)×100 ≥ 5% ただし,%FVCの低下について,測定間隔が365日未満の場合は,以下のとおり相対値で5%以上の低下を必須とする (基点の%FVC - Visit 1の%FVC)/基点の%FVC×100 ≥ 5% 基点のデータは,Visit 1で投与されている抗線維化薬(ニンテダニブ又はピルフェニドン)の投与開始直前又は投与中のデータと定義し,治験担当医師が判断する.なお,基点のデータの測定日とVisit 1の測定間隔は90日以上とする. (6) 以下のとおり,Visit 2のFVCとVisit 1のFVCとの差が+5%以下,又は150 mL以下である (Visit2のFVC - Visit 1のFVC)/Visit1のFVC×100 ≤ 5% 又は,Visit 2のFVC – Visit1のFVC ≤ 150 mL (7) Visit 2の%FVCが50%以上である (8) 一酸化炭素肺拡散能予測値に対する割合(%DLco)[Visit 1のヘモグロビン(Hb)で補正]が25%以上である (9) ILDに対するニンテダニブ,ピルフェニドン以外の治療について,ランダム化割付前42日以内に新たな治療を開始又は,治療を中止していない (10) Visit 1の胸部HRCT画像にて,線維化の程度が気腫性病変の程度より大きい(中央判定を実施するが,最終的には治験担当医師判断とする) (11) 経口投与が可能である |
(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 |
|
(1) TAS-115の投与歴がある (2) 以下に示す治療を本試験のランダム化割付前の規定された期間に受けた a) ランダム化割付前28日以内の大手術(術創はランダム化割付前までに治癒していること) b) ランダム化割付前7日以内のニンテダニブ又はピルフェニドンの投与 c) 本試験のランダム化割付前に他の治験薬の投与を受けてから半減期の5倍の期間が経過していない(半減期が不明の場合は,56日経過していること) (3) 気流閉塞が認められる[Visit 2の気管支拡張剤使用前の1秒率(FEV1/FVC)が0.7未満である] (4) 重度の肺高血圧症と診断されている (5) ILDの急性増悪の既往歴がある (6) TAS-115の成分に対し過敏症の既往歴がある (7) 中等度以上の食欲減退,倦怠感,下痢,悪心,皮膚障害の合併症を有する,又はILDに対する前治療による中等度以上の副作用を有する(脱毛・色素沈着除く) (8) 妊婦及び授乳婦 (9) 以下の期間に適切に避妊することに同意しない男性患者又は妊娠可能な女性患者. 男性患者:治験期間中及び治験薬の最終投与から4ヶ月間 妊娠可能な女性患者:治験期間中及び治験薬の最終投与から7ヶ月間 |
(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 |
|
|
20歳 以上 | 20age old over | |
|
上限なし | No limit | |
|
男性・女性 | Both | |
|
|||
|
進行性フェノタイプを示す慢性線維化性間質性肺疾患 | Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype | |
|
|||
|
|||
|
あり | ||
|
被験薬,用量及び投与方法: TAS-115(投与量1,投与量2又はプラセボ)を1日1回,就寝前の空腹時に経口投与する.5日間の連続投与後,2日間休薬する投与法(5投2休)を繰り返す. 対照薬,用量及び投与方法: ・前治療でニンテダニブを投与している患者 ニンテダニブ(実薬又はプラセボ)を1日2回,食後に経口投与する. ・前治療でピルフェニドンを投与している患者 ピルフェニドン(実薬又はプラセボ)を1日3回,食後に経口投与する. |
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. |
|
|
|||
|
|||
|
26週までのFVC減少率 | 26-week rate of decline in FVC | |
|
52週までのFVC減少率,FVC関連項目,DLco,SpO2,St. George’s Respiratory Questionnaire(SGRQ), 最初の急性増悪までの期間,最初の呼吸器関連の入院までの期間,全生存期間,最初の急性増悪又は死亡までの期間,有害事象,臨床検査値 | 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 |
|
医薬品 | ||
---|---|---|---|
|
未承認 | ||
|
|
|
TAS-115 |
|
なし | ||
|
なし | ||
|
|
||
|
|
あり |
---|
|
||
---|---|---|
|
募集終了 |
Not Recruiting |
|
|
||
---|---|---|
|
|
|
|
||
|
|
大鵬薬品工業株式会社 |
---|---|
|
Taiho Pharmaceutical Co., Ltd. |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
なし | |
---|---|---|
|
||
|
|
神戸市立医療センター西市民病院治験審査委員会 | Kobe City Hospital Organization Kobe City Medical Center West Hospital Institutional Review Board |
---|---|---|
|
兵庫県神戸市長田区一番町2丁目4番地 | 2-4,Ichibancho,Nagata-ku,Kobe, Hyogo |
|
078-576-5251 | |
|
||
|
||
|
承認 |
|
|
---|---|
|
|
|
|
|
|
---|---|---|
|
||
|
||
|
|
無 | No |
---|---|---|
|
本試験についてはIPDデータ共有の計画はございません. 大鵬薬品の治験情報の開示ポリシー https://www.taiho.co.jp/rd/policies_statements/clinicaltrial_disclosure/ | Data will not be shared according to the Sponsor policy on data sharing. Taiho policy on data sharing may be found at https://www.taiho.co.jp/en/science/policy/clinical_trial_information_disclosure_policy/index.html. |
|
|
---|---|
|
|
|
|
設定されていません |
---|---|
|
設定されていません |