JP2023527509A - 全身性硬化症を治療する方法 - Google Patents
全身性硬化症を治療する方法 Download PDFInfo
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- JP2023527509A JP2023527509A JP2022560224A JP2022560224A JP2023527509A JP 2023527509 A JP2023527509 A JP 2023527509A JP 2022560224 A JP2022560224 A JP 2022560224A JP 2022560224 A JP2022560224 A JP 2022560224A JP 2023527509 A JP2023527509 A JP 2023527509A
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Abstract
Description
治療上有効量の2-(4-メトキシ-3-(3-メチルフェネトキシ)ベンズアミド)-2,3-ジヒドロ-1H-インデン-2-カルボン酸(化合物1)
患者に治療上有効な量の2-(4-メトキシ-3-(3-メチルフェネトキシ)ベンズアミド)-2,3-ジヒドロ-1H-インデン-2-カルボン酸(化合物1)
10mg、100mg、150mgまたは200mgの化合物1、および次の賦形剤、マンニトール、微結晶セルロース、クロスポビドン、ヒプロメロース、ステアリン酸マグネシウム、ポビドン、マクロゴール、二酸化チタン、ラウリル硫酸ナトリウム、ならびにドクセートナトリウムを含む、フィルムコーティング錠剤を調製した。
選択的LPAR1受容体拮抗薬である化合物1の活性は、全身性硬化症の患者からの皮膚線維芽細胞、ならびに皮膚、腎臓、および心臓の線維化のいくつかのモデルにおいて評価された。
化合物1を用いた16週間の非盲検延長が続く、8週間の二重盲検、無作為化、プラセボ対照試験は、初期のdcSSc、少なくとも15のベースライン改変Rodnanスキンスコア(mRSS)を有する患者に施される。プライマリーエンドポイントは、試験の二重盲検期間の安全性であった。探索的エンドポイントは、患者の皮膚におけるLPA誘発遺伝シグネチャーの同定を含んだ。
化合物1を用いた52週間の継続が続く、52週間の二重盲検、無作為化、プラセボ対照試験は、初期のdcSScを有し、ベースライン改変Rodnanスキンスコア(mRSS)が少なくとも15であり、少なくとも45%の努力肺活量(FVC)を有する患者に施される。全体の目標は、対象の治療において、52週間、1日1回(QD)、または1日2回(BID)投与される、化合物1の2つの投与計画の、効能、安全性、および許容度を調査することである。第1の目的は、52週間の治療後の、予測されたFVC%の変化の比較により決定されるように、dcSScを用いて、対象においてHZN-825対プラセボの1つ、あるいは2つの投与計画の効能を実証することである。上記に定義されたように、付加エンドポイントはまた、捕捉され、および評価される(例えば、HAQ-DI、SS-PRO、ACR-CRISS、など)。
Claims (14)
- 前記全身性硬化症が、限局性皮膚全身性硬化症、びまん性皮膚全身性硬化症、および全身性硬化症サイン強皮症から選択される、請求項1に記載の方法。
- 前記全身性硬化症が、びまん性皮膚全身性硬化症である、請求項2に記載の方法。
- 前記全身性硬化症が、早期皮膚びまん性全身性硬化症である、請求項3に記載の方法。
- 前記投与期間が、少なくとも36週間である、請求項1から4のいずれか一項に記載の方法。
- 前記投与期間が、少なくとも52週間である、請求項1から5のいずれか一項に記載の方法。
- 化合物1またはその薬学的に許容される塩が、経口投与される、請求項1から6のいずれか一項に記載の方法。
- (遊離酸換算重量ベースで)300mgの化合物1またはその薬学的に許容される塩が、少なくとも1日1回投与される、請求項7に記載の方法。
- (遊離酸換算重量ベースで)300mgの化合物1またはその薬学的に許容される塩が、1日2回投与される、請求項7に記載の方法。
- 1つ以上の追加の治療を施すことをさらに含む、請求項1から9のいずれか一項に記載の方法。
- 前記1つ以上の追加の治療は、免疫抑制薬、T細胞指向性治療薬、B細胞指向性治療薬、自己造血幹細胞移植、ケモカイン配位子受容体拮抗薬、DNAメチル化阻害剤、ヒストンデアセチラーゼ阻害剤、スタチン、エンドセリン受容体拮抗薬、V型ホスホジエステラーゼ阻害剤、プロスタサイクリンアナログ、サイトカインの合成および/もしくはシグナル伝達の阻害剤、コルチコステロイド、非ステロイド系抗炎症薬、光線療法、ならびに血圧治療薬から選択される、請求項10に記載の方法。
- 化合物1またはその薬学的に許容される塩による前記治療が、0.60以上のCRISSスコアをもたらす、請求項1から11のいずれか一項に記載の方法。
- 化合物1またはその薬学的に許容される塩による前記治療が、mRSS変化が5以上と測定されるように、皮膚線維症の減少をもたらす、請求項1から12のいずれか一項に記載の方法。
- 化合物1またはその薬学的に許容される塩による前記治療が、0.14以上のHAQ-DIの改善をもたらす、請求項1から13のいずれか一項に記載の方法。
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