Clinical Study to Investigate the PK, Efficacy, and Safety of Wilate in Patients With Severe Hemophilia A
2020年12月21日 更新者：Octapharma
Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Patients With Severe Hemophilia A
The purpose of this study is to obtain additional data on the safety and efficacy of Wilate in PTPs with hemophilia A with at least 150 previous exposure days (EDs) to a FVIII concentrate who undergo prophylactic treatment with Wilate for 6 months and at least 50 EDs, thus supplementing the existing database to obtain approval of Wilate for the indication hemophilia A in the USA.
調査の概要
研究の種類
介入
入学 (実際)
57
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Budapest、ハンガリー
- National Haemophilia Centre
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Sofia、ブルガリア
- Specialized Hospital for Active Treatment "Joan Pavel"
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Krakow、ポーランド
- Krakowskie Centrum Medyczne
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Rzeszow、ポーランド
- Korczowski Bartosz Gabinet Lekarski
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Bucharest、ルーマニア
- Centrul Medical Unirea -Policlinica Enescu
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Barnaul、ロシア連邦
- Barnaul Branch of RAMS hematology center
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Moscow、ロシア連邦
- Federal Scientific Hematology Center
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
12年歳以上 (子、大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
男
説明
Inclusion Criteria:
- Severe hemophilia A (<1% FVIII:C) according to medical history
- Male patients aged ≥12 years
- Previous treatment with a FVIII concentrate for at least 150 exposure days (EDs)
- Immunocompetence (CD4+ count >200/µL)
- Good documentation of the historical bleeding rate (at least for the 6 months preceding study start)
- Voluntarily given, fully informed written and signed consent obtained by the patient (or parent/legal guardian in case of adolescents) before any study-related procedures are conducted
Whenever possible, the interval between the Screening Visit and the PK or Non-PK Visit should not exceed 30 days. If the 30-day interval is exceeded, determination of the CD4+ count is to be repeated and must be >200/µL for patients to be enrolled (i.e., exclusion criterion no. 4).
Exclusion Criteria:
- Any coagulation disorders other than hemophilia A
- History of FVIII inhibitor activity (≥0.6 BU) or detectable FVIII inhibitory anti-bodies (≥0.6 BU using the Nijmegen modification of the Bethesda assay) at screening, as determined by the central laboratory
- Severe liver or kidney diseases (alanine aminotransferase [ALAT] and aspartate transaminase [ASAT] levels >5 times of upper limit of normal, creatinine>120 µmol/L)
- Patients receiving or scheduled to receive immunomodulating drugs (other than anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to >10 mg/day), or similar drugs
- Treatment with any investigational medicinal product in another interventional clinical study currently or within 4 weeks before enrollment
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：All patients
All patients will receive Wilate for prophylactic treatment
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他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Total Annualized Bleeding Rate (TABR)
時間枠：6 months
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The total number of bleeding events (BEs) was documented by patients in a patient diary (together with the investigator in case of on-site treatments), which was reviewed at each follow-up visit by site personnel.
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6 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Spontaneous Annualized Bleeding Rate (SABR)
時間枠：6 months
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The number of spontaneous bleeding events (BEs) was documented by patients in a patient diary (together with the investigator in case of on-site treatments), which was reviewed at each follow-up visit by site personnel.
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6 months
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Efficacy of Wilate in the Treatment of Breakthrough BEs
時間枠：6 months
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The proportion of BEs successfully treated with Wilate were documented by the patient (together with the investigator in case of on-site treatments) in the patient diary for all BEs according to a 4-point hemostatic efficacy scale including the four items: 'excellent,' 'good,' moderate,' and 'none', where 'excellent' was defined as "Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection" (best outcome) and 'none' was defined as "No improvement within 12 hours, or worsening of symptoms, requiring more than two injections for complete resolution" (worst outcome).
All efficacy ratings assessed as either 'excellent' or 'good' were considered 'successfully treated.'
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6 months
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Wilate Consumption Data (Average Total Normdose of FVIII IU/kg Per Month of Study) for Prophylaxis
時間枠：6 months
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The average consumption of Wilate per month of study (IU/kg) for all patients receiving prophylaxis.
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6 months
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Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Norm) of FVIII:C
時間枠：Initial PK visit (Day -1) and PK study completion visit (6 months); data collected 1 h prior to injection and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
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PK assessments of FVIII:C were conducted using the one-stage (OS) assay.
The value of the AUCnorm of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study.
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Initial PK visit (Day -1) and PK study completion visit (6 months); data collected 1 h prior to injection and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
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Pharmacokinetic (PK) Assessment (in Vivo Half-Life (t1/2)) of FVIII:C
時間枠：Initial PK assessment (Day -1) and PK study completion visit (6 months); data collected 1 h prior to infusion and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
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PK assessments of FVIII:C were conducted using the one-stage (OS) assay.
The in vivo half-life of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study.
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Initial PK assessment (Day -1) and PK study completion visit (6 months); data collected 1 h prior to infusion and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
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Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration [Cmax]) of FVIII:C
時間枠：Initial PK assessment (Day -1) and 6 months
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PK assessments of FVIII:C were conducted using the one-stage (OS) assay.
The maximum plasma concentration of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study.
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Initial PK assessment (Day -1) and 6 months
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Incremental in Vivo Recovery (IVR) of Wilate Over Time
時間枠：Baseline, 3 and 6 months
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The rise in FVIII activity in IU/dl per unit dose administered in IU/kg was determined from all patients at baseline, 3 and 6 months, using the OS assay.
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Baseline, 3 and 6 months
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Association Between ABO Blood Type and the FVIII:C Half-life of Wilate (OS Assay)
時間枠：6 months
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Analysis of variance (ANOVA) was used in an exploratory sense to assess an association between ABO blood type and the FVIII:C half-life of Wilate.
This was analyzed by calculating the mean square in a one-stage assay.
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6 months
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Association Between VWF:Ag Concentration and the FVIII:C Half-life of Wilate
時間枠：6 months
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ANOVA was used in an exploratory sense to assess an association between VWF:Ag with the FVIII:C half-life of Wilate.
This was analyzed by calculating the mean square in a one-stage assay.
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6 months
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Safety and Tolerability of Wilate by Monitoring Adverse Events (AEs) Throughout the Study
時間枠：6 months
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At each (scheduled or unscheduled) study visit, AEs were documented by the investigator throughout the study.
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6 months
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Immunogenicity of Wilate by Testing for FVIII Inhibitors
時間枠：6 months
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FVIII inhibitor activity was determined at each study visit before the injection of Wilate using the modified Bethesda assay (Nijmegen modification).
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6 months
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Virus Safety Measured by the Number of Parvovirus B19 Seroconversions Between Baseline (BL) and End of Study
時間枠：6 months
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Virus safety was evaluated by taking a plasma sample for parvovirus B19 antibody testing before the first injection of Wilate.
All patients negative at screening were tested again at the study completion visit.
The number with Parvovirus B19 seroconversions between BL and end of study was recorded.
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6 months
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Efficacy of Wilate in Surgical Prophylaxis
時間枠：6 months
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Hemostatic efficacy was assessed at the end of surgery by the surgeon and at end of the postoperative period by the hematologist, using a 4-point hemostatic efficacy scale including the four items: 'excellent' (best possible outcome), 'good', 'moderate' and 'none' (worst outcome).
Overall efficacy was assessed by the investigator, taking both the intra and postoperative assessments into account, and using the 'excellent,' 'good,' moderate,' and 'none' scale.
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6 months
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2016年12月1日
一次修了 (実際)
2018年3月29日
研究の完了 (実際)
2018年3月29日
試験登録日
最初に提出
2016年10月27日
QC基準を満たした最初の提出物
2016年11月1日
最初の投稿 (見積もり)
2016年11月3日
学習記録の更新
投稿された最後の更新 (実際)
2021年1月19日
QC基準を満たした最後の更新が送信されました
2020年12月21日
最終確認日
2020年12月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
重度の血友病Aの臨床試験
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King Saud University完了
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Cheikh Anta Diop University, SenegalInternational Atomic Energy Agencyまだ募集していません
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Medical University of Vienna完了
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University of California, DavisBill and Melinda Gates Foundation; Penn State University; Newcastle University; Helen Keller International と他の協力者完了
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Institute of Nutrition of Central America and PanamaBill and Melinda Gates Foundation; Newcastle University; International Atomic Energy Agency完了
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University of California, DavisHelen Keller International完了
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Tufts UniversityNutricia Research Fundation; National University of Science and Technology, Zimbabwe完了
Wilateの臨床試験
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Octapharma完了フォン・ヴィレブランド病アメリカ, カナダ, スウェーデン, スペイン, ウルグアイ, イギリス, ポルトガル, アルゼンチン, チェコ, ドイツ
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BloodworksErgomed; Octapharma; Mary M. Gooley Hemophilia Center募集