Evaluating the Safety and Efficacy of Romiplostim (AMG 531) in Thrombocytopenic Subjects With Immune Thrombocytopenic Purpura (ITP)
2019年12月20日 更新者：Amgen
A Dose-finding Study Evaluating the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects With Immune Thrombocytopenic Purpura (ITP)
The primary objective of this study is to evaluate the safety and tolerability of romiplostim in thrombocytopenic patients with ITP.
調査の概要
研究の種類
介入
入学 (実際)
45
段階
- フェーズ2
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
18年～65年 (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
全て
説明
Inclusion Criteria:
- Diagnosis of ITP according to American Society of Hematology (ASH) guidelines at least 3 months before enrollment
- Have completed at least 1 prior treatment for ITP
Two (including day -2) of the 3 platelet counts taken during the screening and pre-treatment periods must have fulfilled the following:
- less than 30 x 10^9/L for those subjects not receiving any ITP therapy,
- less than 50 x 10^9/L for those subjects receiving any ITP therapy
- Eastern Cooperative Oncology Group performance status of 0 to 2
- Serum creatinine concentration ≤ 2 mg/dL (≤ 176.8 µmol/L)
- Adequate liver function, as evidenced by a serum bilirubin ≤ 1.5 times the laboratory normal range
- Hemoglobin greater than 10.0 g/dL
- Written informed consent
Exclusion Criteria:
- Considered a substantial risk for adverse outcomes because of a clinically important trend (as determined by the investigator) detected in the platelet counts during the screening period
- Any known history of bone marrow stem cell disorder
- Any active malignancy. If prior history of cancer other than basal cell carcinoma or cervical carcinoma in situ, no treatment or active disease within 5 years before randomization
- Documented diagnosis of arterial thrombosis (ie, stroke, transient ischemic attack, or myocardial infarction) in the previous year; history of venous thrombosis (ie, deep vein thrombosis, pulmonary embolism) and receiving anticoagulation therapy
- Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure [New York Heart Association (NYHA) greater than class II], uncontrolled hypertension [diastolic greater than 100 mmHg] or cardiac arrhythmia)
- Have 3 or more of the following predisposing factors for thromboembolic events: diabetes; smoker using oral contraceptives; hypercholesteremia (> 240 mg/dL); treatment for hypertension
- Known positive test for human immunodeficiency virus (HIV) infection or hepatitis C virus
- Received any treatment for ITP (except for a constant dose schedule of corticosteroids) within 4 weeks before the screening visit
- Received intravenous (IV) immunoglobulin (Ig) or WinRho within 2 weeks before the screening visit
- Received hematopoietic growth factors, including interleukin (IL)-11 (Neumega®) within 4 weeks before the screening visit
- Past or present participation in any study evaluating polyethylene glycol recombinant human magakaryopoiesis differentiating factor (PEG-rHuMGDF), recombinant human thrombopoietin (rHuTPO), or related platelet product
- Received any alkylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study
- Received any monoclonal antibody (eg, rituximab) within 16 weeks before the screening visit or anticipated use during the time of the proposed study
- Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication before the screening period
- Less than 2 months since major surgery (including laparoscopic splenectomy)
- Pregnant or breast feeding
- Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator
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：ランダム化
- 介入モデル：順次割り当て
- マスキング：ダブル
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：Part A: Romiplostim 0.2 µg/kg
Participants received 0.2 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.
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Administered by subcutaneous injection
他の名前：
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実験的：Part A: Romiplostim 0.5 µg/kg
Participants received 0.5 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.
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Administered by subcutaneous injection
他の名前：
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実験的：Part A: Romiplostim 1.0 µg/kg
Participants received 1.0 µg/kg romiplostim subcutaneously on day 1 and on day 15 or 22 depending on platelet counts.
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Administered by subcutaneous injection
他の名前：
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実験的：Part A: Romiplostim 3 µg/kg
Participants received 3.0 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.
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Administered by subcutaneous injection
他の名前：
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実験的：Part A: Romiplostim 6 µg/kg
Participants received 6.0 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.
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Administered by subcutaneous injection
他の名前：
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実験的：Part A: Romiplostim 10 µg/kg
Participants received 10.0 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.
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Administered by subcutaneous injection
他の名前：
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プラセボコンパレーター：Part B: Placebo
Participants received placebo subcutaneously once a week for 6 weeks.
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皮下注射による投与
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実験的：Part B: Romiplostim 1.0 µg/kg
Participants received 1.0 µg/kg subcutaneously once a week for 6 weeks.
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Administered by subcutaneous injection
他の名前：
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実験的：Part B: Romiplostim 3.0 µg/kg
Participants received 3.0 µg/kg subcutaneously once a week for 6 weeks.
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Administered by subcutaneous injection
他の名前：
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実験的：Part B: Romiplostim 6.0 µg/kg
Participants received 6.0 µg/kg subcutaneously once a week for 6 weeks.
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Administered by subcutaneous injection
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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Number of Participants With Adverse Events
時間枠：From first dose of study drug through 8 weeks (Part A) or 6 weeks (Part B) after last dose of study drug; 78 days
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From first dose of study drug through 8 weeks (Part A) or 6 weeks (Part B) after last dose of study drug; 78 days
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Number of Participants With Anti-romiplostim or Anti-endogenous Thrombopoietin Neutralizing Antibodies
時間枠：Assessed on day 29 (Part A only), day 43 (Part B only), and day 78
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The development of antibodies to romiplostim or to endogenous thrombopoietin (eTPO) was assessed using a neutralizing bioassay.
Participants positive for neutralizing antibodies at any of the assessments during the study are reported.
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Assessed on day 29 (Part A only), day 43 (Part B only), and day 78
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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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Number of Participants Who Achieved Targeted Therapeutic Platelet Level in Part A
時間枠：After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Targeted therapeutic platelet level was defined as a doubling of baseline platelet counts and between 50 to 450 x 10⁹ cells/L. Platelet count data after the use of rescue medication were not included; participants with no platelet count data were considered non-responders. |
After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Number of Participants With an Increase in Platelet Count of ≥ 20 x 10⁹ Cells/L Over Baseline in Part A
時間枠：After first dose (day 1 to day 15 or 22), and after second dose (day 15 or 22 to day 78)
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Platelet count data after the use of rescue medication were not included; participants with no platelet count data were considered non-responders.
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After first dose (day 1 to day 15 or 22), and after second dose (day 15 or 22 to day 78)
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Number of Participants With a Peak Platelet Count ≥ 100 x 10⁹ Cells/L in Part A
時間枠：After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Platelet count data after the use of rescue medication were not included; participants with no platelet count data were considered non-responders.
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After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Number of Participants With a Peak Platelet Count of > 450 x 10⁹ Cells/L in Part A
時間枠：After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Platelet count data after the use of rescue medication were not included; participants with no platelet count data were considered non-responders.
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After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Peak Platelet Count After Each Dose in Part A
時間枠：After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Platelet count data after the use of rescue medication were not included.
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After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Change From Baseline in Peak Platelet Count After Each Dose in Part A
時間枠：Baseline and after first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Platelet count data after the use of rescue medication were not included.
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Baseline and after first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Time to Peak Platelet Count After Each Dose in Part A
時間枠：After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Platelet count data after the use of rescue medication were not included.
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After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Duration Within the Targeted Therapeutic Platelet Range In Part A
時間枠：After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Targeted therapeutic platelet level was defined as a platelet count that was double the baseline level and ≥ 50 and ≤ 450 × 10⁹ cells/L. Platelet count data after the use of rescue medication were not included. |
After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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Percentage of Participants Who Achieved Targeted Therapeutic Platelet Level In Part B
時間枠：Day 1 to day 78
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Targeted therapeutic platelet level was defined as a doubling of baseline platelet counts and within the range of greater than or equal to 50 x 10⁹ cells/L and less than or equal to 450 x 10⁹ cells/L. Platelet count data after use of rescue medication were not included in the analysis. |
Day 1 to day 78
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Percentage of Participants With an Increase in Platelet Count of ≥ 20 x 10⁹ Cells/L Over Baseline in Part B
時間枠：Day 1 to day 78
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Platelet count data after administration of rescue medication were not included in the analysis.
Participants with no platelet count data were considered non-responders.
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Day 1 to day 78
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Percentage of Participants With a Peak Platelet Count of ≥ 100 x 10⁹ Cells/L in Part B
時間枠：Day 1 to day 78
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Platelet count data after administration of rescue medication were not included in the analysis.
Participants with no platelet count data were considered non-responders.
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Day 1 to day 78
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Percentage of Participants With a Peak Platelet Count of > 450 x 10⁹ Cells/L in Part B
時間枠：Day 1 to day 78
|
Platelet count data after administration of rescue medication were not included in the analysis.
Participants with no platelet count data were considered non-responders.
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Day 1 to day 78
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Percentage of Participants With a Peak Platelet Count of > 500 x 10⁹ Cells/L in Part B
時間枠：Day 1 to day 78
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Platelet count data after administration of rescue medication were not included in the analysis.
Participants with no platelet count data were considered non-responders.
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Day 1 to day 78
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Peak Platelet Count in Part B
時間枠：Day 1 to day 78
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Platelet count data after administration of rescue medication were not included in the analysis.
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Day 1 to day 78
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Change From Baseline in Peak Platelet Count in Part B
時間枠：Baseline and day 1 to day 78
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Platelet count data after administration of rescue medication were not included in the analysis.
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Baseline and day 1 to day 78
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Time to Peak Platelet Count in Part B
時間枠：Day 1 to day 78
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Platelet count data after administration of rescue medication were not included in the analysis.
Time to peak platelet count was analyzed using the Kaplan-Meier method.
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Day 1 to day 78
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Duration Within the Targeted Therapeutic Platelet Range in Part B
時間枠：Day 1 to day 78
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Targeted therapeutic platelet level was defined as a doubling of baseline platelet counts and within the range of greater than or equal to 50 × 10⁹ cells/L and less than or equal to 450 × 10⁹ cells/L. Platelet count data after administration of rescue medication were not included in the analysis. |
Day 1 to day 78
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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
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Cines DB, Wasser J, Rodeghiero F, Chong BH, Steurer M, Provan D, Lyons R, Garcia-Chavez J, Carpenter N, Wang X, Eisen M. Safety and efficacy of romiplostim in splenectomized and nonsplenectomized patients with primary immune thrombocytopenia. Haematologica. 2017 Aug;102(8):1342-1351. doi: 10.3324/haematol.2016.161968. Epub 2017 Apr 14.
- Bussel JB, Kuter DJ, George JN, McMillan R, Aledort LM, Conklin GT, Lichtin AE, Lyons RM, Nieva J, Wasser JS, Wiznitzer I, Kelly R, Chen CF, Nichol JL. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med. 2006 Oct 19;355(16):1672-81. doi: 10.1056/NEJMoa054626. Erratum In: N Engl J Med. 2006 Nov 9;355(19):2054.
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)
2002年7月1日
一次修了 (実際)
2004年6月17日
研究の完了 (実際)
2004年6月17日
試験登録日
最初に提出
2005年5月20日
QC基準を満たした最初の提出物
2005年5月20日
最初の投稿 (見積もり)
2005年5月23日
学習記録の更新
投稿された最後の更新 (実際)
2020年1月10日
QC基準を満たした最後の更新が送信されました
2019年12月20日
最終確認日
2019年12月1日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 20000137
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。