JP2019533004A - hGH融合タンパク質を含有する、成長ホルモン欠乏症を治療するための医薬組成物 - Google Patents
hGH融合タンパク質を含有する、成長ホルモン欠乏症を治療するための医薬組成物 Download PDFInfo
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- A—HUMAN NECESSITIES
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Abstract
Description
[20]本開示の目的は、hGH融合タンパク質GX−H9の用量および投薬頻度を明らかにすることによって、成長ホルモン欠乏症を治療するのに効果的なhGH融合タンパク質GX−H9を使用して成長ホルモン欠乏症を治療するための方法を提供することである。
[59]以下、本開示を、例を参照してさらに詳細に記載する。これらの例は、例示のみを目的とし、本開示の範囲を限定すると解釈されるべきではないことが、当業者には明らかである。
[62]hGH融合タンパク質GX−H9は、米国特許第8,529,899号に開示されている方法に従って生成することができる。
[69]GX−H9のハイブリッドFc領域が、抗体依存性細胞媒介性細胞傷害(ADCC)および補体依存性細胞傷害(CDC)を誘導しないことを確認するために、酵素連結免疫測定法アッセイ(ELISA)を実施した。
[75]3−1:下垂体切除ラットを使用したGX−H9の反復皮下投与の効果に関する試験
[76]GX−H9の効果を、動物疾患モデルである下垂体切除ラットを使用して試験した。対照として、毎日1回用量形態のGenotropin(Pfizer、USA)を使用した。GX−H9を1週間に1回投与し、その効果を、対照の効果と比較した。
[81]GX−H9の薬物動態を試験するために、ラットに、単回用量のGX−H9を皮下投与した。対照として、効果の比較のために単回用量のEutropin(LG Life Sciences,Ltd.、Korea)をラットに投与した。群1には、単回用量の200μg/kgのEutropinを皮下投与し、群2には、単回用量の200μg/kgのGX−H9を皮下投与した。群3には、単回用量の1,000μg/kgのGX−H9を皮下投与した。
[90]カニクイザルにおけるGX−H9および対照物質Eutropinの薬物動態を分析した。雄性のサル(群あたり3匹のサル)に、GX−H9を、500μg/kgおよび1,000μg/kgの用量で1週間に1回、合計4回反復して皮下投与し、対照物質Eutropinを、1,000μg/kgの単回用量で皮下投与した。
[102]4−1:健康な成人におけるhGH融合タンパク質(GX−H9)の薬物動態特性
[103]健康なボランティアに対し、無作為割当て、二重盲検、プラセボ対照、単回用量投与および用量の段階的増加を使用して、第1相臨床研究を実施した。第1相臨床研究は、GX−H9の単回用量投与に対する、安全性、薬物耐性および薬物動態/薬力学特性を評価することが目的であった。健康なボランティアを、無作為に試験群またはプラセボ群に割り当て、次いで、4種の用量(0.2、0.4、0.8および1.6mg/kg)のGX−H9を単回容量で皮下投与し、次いで、合計で56日間にわたって評価した。
GX−H9を投与した群では、血液を、単回用量投与前、ならびに単回用量投与後12、24、36、48、60、72、96、144、312、480、648および1320時間の時点でサンプリングした。投与前に測定したサンプリングした血液におけるIGF−1濃度に対するベースラインからのパーセント変化の結果を、図8に示す。
試験対象において観察された、治療により出現した有害事象を、投与薬物、有害事象と薬物との関係および有害事象の強度に従って分析した。結果を以下の表5にまとめる。
[122]n=有害事象を示した人数;
[123]E=出現した有害事象数;
[124](%)=治療から生じた有害事象を経験した患者のパーセンテージ、(n/N)×100;
[125]深刻な有害事象または軽度の有害事象は記録されなかった。
[130]5−1:小児成長ホルモン欠乏症を有する患者におけるhGH融合タンパク質(GX−H9)の薬物動態特性
[131]無作為化、非盲検、実薬対照、用量設定試験において、1週間に1回または2週間に1回投与した場合のGX−H9の安全性、薬物耐性、有効性および薬物動態/薬力学特性を評価するために、小児成長ホルモン欠乏症を有する患者に対する第2相臨床研究が進行中である。GX−H9を、0.8mg/kgの用量で1週間に1回、1.2mg/kgの用量で1週間に1回、および2.4mg/kgの用量で2週間に1回、合計6ヶ月にわたって投与し、次いで、GX−H9の有効性および安全性を、投与の18ヶ月の延長を含む合計24ヶ月にわたって評価した。対照薬として、Genotropinを0.03mg/kgの用量で毎日、12ヶ月にわたって投与した。
[142]融合タンパク質の薬力学特性の分析を、例5−1で上記した通りの薬力学分析のための血液サンプリングタイミングと同じタイミングで実施した。
[153]試験対象において観察された有害事象を。投与薬物および薬物と有害事象との関係に従って分析した。結果として、小児患者に対する臨床研究において現在までに報告されたすべての有害事象は、既存の成長ホルモン治療において観察されるものと同じレベルであり、GX−H9が安全であることを示した。
[156]免疫原性を、GX−H9の反復投与によって抗体が形成されるかを決定することによって評価した。現在まで、GX−H9の投与によって形成された抗体は、何れの患者においても観察されなかった。
[163]電子ファイル添付。
Claims (10)
- 成長ホルモン欠乏症を治療するための医薬組成物であって、ヒト成長ホルモン(hGH)とハイブリッドFcの融合タンパク質であるhGH融合タンパク質GX−H9、および薬学的に許容される担体を含み、前記hGH融合タンパク質が、患者の体重1kgあたり0.4〜1.6mgの用量で1週間に1回投与される、医薬組成物。
- 前記hGH融合タンパク質が、前記患者の体重1kgあたり0.5〜1.5mgの用量で1週間に1回投与される、請求項1に記載の医薬組成物。
- 成長ホルモン欠乏症を治療するための医薬組成物であって、ヒト成長ホルモン(hGH)とハイブリッドFcの融合タンパク質であるhGH融合タンパク質GX−H9、および薬学的に許容される担体を含み、前記hGH融合タンパク質(GX−H9)が、患者の体重1kgあたり0.8〜3.2mgの用量で2週間に1回投与される、医薬組成物。
- 前記hGH融合タンパク質が、前記患者の体重1kgあたり1.0〜3.0mgの用量で1週間に1回投与される、請求項3に記載の医薬組成物。
- 前記hGH融合タンパク質が、配列番号1のアミノ酸配列を含む、請求項1〜4の何れか一項に記載の医薬組成物。
- 前記医薬組成物が皮下投与される、請求項1〜4の何れか一項に記載の医薬組成物。
- 成長ホルモン欠乏症を治療するための方法であって、hGH融合タンパク質GX−H9を、成長ホルモン欠乏症を有する患者に、前記患者の体重1kgあたり0.4〜1.6mgの用量で1週間に1回投与する工程を含む方法。
- 成長ホルモン欠乏症を治療するための方法であって、hGH融合タンパク質GX−H9を、成長ホルモン欠乏症を有する患者に、前記患者の体重1kgあたり0.8〜3.2mgの用量で2週間に1回投与する工程を含む、方法。
- ヒト成長ホルモン(hGH)とハイブリッドFcの融合タンパク質であるhGH融合タンパク質GX−H9および薬学的に許容される担体を含む容器、ならびに前記hGH融合タンパク質が、成長ホルモン欠乏症を治療するために、患者に、前記患者の体重1kgあたり0.4〜1.6mg/kgの用量で1週間に1回投与されることを示す添付文書を含むキット。
- ヒト成長ホルモン(hGH)とハイブリッドFcの融合タンパク質であるhGH融合タンパク質GX−H9および薬学的に許容される担体を含む容器、ならびに前記hGH融合タンパク質が、成長ホルモン欠乏症を治療するために、患者に、前記患者の体重1kgあたり0.8〜3.2mg/kgの用量で2週間に1回投与されることを示す添付文書を含むキット。
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TW201925237A (zh) | 2019-07-01 |
JP2023061978A (ja) | 2023-05-02 |
EP3506923B1 (en) | 2022-07-27 |
KR102309668B1 (ko) | 2021-10-07 |
JP7333519B2 (ja) | 2023-08-25 |
CN110177567A (zh) | 2019-08-27 |
JOP20190019A1 (ar) | 2019-02-12 |
DK3506923T3 (da) | 2022-08-29 |
RU2748402C2 (ru) | 2021-05-25 |
TW201924714A (zh) | 2019-07-01 |
US20190224281A1 (en) | 2019-07-25 |
RU2019109154A3 (ja) | 2020-12-30 |
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