- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT00111475
Evaluating the Safety and Efficacy of Romiplostim (AMG 531) in Thrombocytopenic Subjects With Immune Thrombocytopenic Purpura (ITP)
A Dose-finding Study Evaluating the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects With Immune Thrombocytopenic Purpura (ITP)
Přehled studie
Postavení
Intervence / Léčba
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 2
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Sekvenční přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
---|---|
Experimentální: 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.
|
Administered by subcutaneous injection
Ostatní jména:
|
Experimentální: 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.
|
Administered by subcutaneous injection
Ostatní jména:
|
Experimentální: 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.
|
Administered by subcutaneous injection
Ostatní jména:
|
Experimentální: 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.
|
Administered by subcutaneous injection
Ostatní jména:
|
Experimentální: 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.
|
Administered by subcutaneous injection
Ostatní jména:
|
Experimentální: 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.
|
Administered by subcutaneous injection
Ostatní jména:
|
Komparátor placeba: Part B: Placebo
Participants received placebo subcutaneously once a week for 6 weeks.
|
Podává se subkutánní injekcí
|
Experimentální: Part B: Romiplostim 1.0 µg/kg
Participants received 1.0 µg/kg subcutaneously once a week for 6 weeks.
|
Administered by subcutaneous injection
Ostatní jména:
|
Experimentální: Part B: Romiplostim 3.0 µg/kg
Participants received 3.0 µg/kg subcutaneously once a week for 6 weeks.
|
Administered by subcutaneous injection
Ostatní jména:
|
Experimentální: Part B: Romiplostim 6.0 µg/kg
Participants received 6.0 µg/kg subcutaneously once a week for 6 weeks.
|
Administered by subcutaneous injection
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Number of Participants With Adverse Events
Časové okno: From first dose of study drug through 8 weeks (Part A) or 6 weeks (Part B) after last dose of study drug; 78 days
|
From first dose of study drug through 8 weeks (Part A) or 6 weeks (Part B) after last dose of study drug; 78 days
|
|
Number of Participants With Anti-romiplostim or Anti-endogenous Thrombopoietin Neutralizing Antibodies
Časové okno: Assessed on day 29 (Part A only), day 43 (Part B only), and day 78
|
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.
|
Assessed on day 29 (Part A only), day 43 (Part B only), and day 78
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Number of Participants Who Achieved Targeted Therapeutic Platelet Level in Part A
Časové okno: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
|
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)
|
Number of Participants With an Increase in Platelet Count of ≥ 20 x 10⁹ Cells/L Over Baseline in Part A
Časové okno: After first dose (day 1 to day 15 or 22), and after second dose (day 15 or 22 to day 78)
|
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)
|
Number of Participants With a Peak Platelet Count ≥ 100 x 10⁹ Cells/L in Part A
Časové okno: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
|
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)
|
Number of Participants With a Peak Platelet Count of > 450 x 10⁹ Cells/L in Part A
Časové okno: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
|
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)
|
Peak Platelet Count After Each Dose in Part A
Časové okno: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
|
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)
|
Change From Baseline in Peak Platelet Count After Each Dose in Part A
Časové okno: Baseline and after first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
|
Platelet count data after the use of rescue medication were not included.
|
Baseline and after first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
|
Time to Peak Platelet Count After Each Dose in Part A
Časové okno: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
|
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)
|
Duration Within the Targeted Therapeutic Platelet Range In Part A
Časové okno: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
|
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)
|
Percentage of Participants Who Achieved Targeted Therapeutic Platelet Level In Part B
Časové okno: Day 1 to day 78
|
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
|
Percentage of Participants With an Increase in Platelet Count of ≥ 20 x 10⁹ Cells/L Over Baseline in Part B
Časové okno: 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.
|
Day 1 to day 78
|
Percentage of Participants With a Peak Platelet Count of ≥ 100 x 10⁹ Cells/L in Part B
Časové okno: 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.
|
Day 1 to day 78
|
Percentage of Participants With a Peak Platelet Count of > 450 x 10⁹ Cells/L in Part B
Časové okno: 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.
|
Day 1 to day 78
|
Percentage of Participants With a Peak Platelet Count of > 500 x 10⁹ Cells/L in Part B
Časové okno: 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.
|
Day 1 to day 78
|
Peak Platelet Count in Part B
Časové okno: Day 1 to day 78
|
Platelet count data after administration of rescue medication were not included in the analysis.
|
Day 1 to day 78
|
Change From Baseline in Peak Platelet Count in Part B
Časové okno: Baseline and day 1 to day 78
|
Platelet count data after administration of rescue medication were not included in the analysis.
|
Baseline and day 1 to day 78
|
Time to Peak Platelet Count in Part B
Časové okno: Day 1 to day 78
|
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.
|
Day 1 to day 78
|
Duration Within the Targeted Therapeutic Platelet Range in Part B
Časové okno: Day 1 to day 78
|
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
|
Spolupracovníci a vyšetřovatelé
Sponzor
Publikace a užitečné odkazy
Obecné publikace
- 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.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Patologické procesy
- Onemocnění imunitního systému
- Autoimunitní onemocnění
- Hematologická onemocnění
- Krvácení
- Hemoragické poruchy
- Poruchy srážení krve
- Kožní projevy
- Trombocytopenie
- Poruchy krevních destiček
- Trombotické mikroangiopatie
- Purpura
- Purpura, trombocytopenická
- Purpura, trombocytopenická, idiopatická
Další identifikační čísla studie
- 20000137
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