Amgen Megakaryopoiesis Protein 2 (AMG 531) in Thrombocytopenic Subjects With Immune Thrombocytopenic Purpura (ITP)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of AMG 531 (romiplostim), a novel thrombopoiesis-stimulating peptibody, and its effect on platelet counts in adults with immune thrombocytopenic purpura.

Official Title
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An Open-label, Unit Dose-finding Study Evaluating the Safety and Efficacy of Amgen Megakaryopoiesis Protein 2 (AMG 531) in Thrombocytopenic Subjects With Immune Thrombocytopenic Purpura (ITP)

Conditions
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Thrombocytopenic Purpura

Intervention / Treatment
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* Drug: Romiplostim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Greater than or equal to 3 months history of ITP, regardless of splenectomy status, and completion of at least 1 prior treatment for ITP 2 of 3 pretreatment platelet counts that were less than 30 x 10^9/L (if not currently on ITP therapy) or less than 50 x 10^9/L (if currently receiving corticosteroids for ITP therapy) Ability to give informed consent Exclusion Criteria: Known history of arterial thrombosis, active malignancy, or bone marrow stem cell disorder

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romiplostim<br>Participants will receive a maximum of 2 administrations of romiplostim by subcutaneous injection, the first on day 1 of the study and the second on day 15 or 22 depending on the participant's platelet count. Romiplostim doses to be tested were 30, 100, 300, and 500 μg. | Drug: Romiplostim<br>* Administered subcutaneously on day 1 and on day 15 or 22 if the platelet count was ≤ 50 x 10⁹/L and not rising, peak platelet count was ≤ 450 x 10⁹/L and no serious adverse events related to treatment were observed.<br>* Other names: NPLATE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events |  | From first dose through 8 weeks after last dose of study drug (11 weeks) | 
| Number of Participants With Positive Anti-Romiplostim Antibodies | The presence or development of antibodies to romiplostim and endogenous thrombopoietin was assessed using a neutralizing bioassay. Antibody analyses were conducted on study days 29 and at the end-of-study visit (day 78). The number of participants with positive antibody binding at any time during the study is reported. | Days 29 and 78 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved a Targeted Therapeutic Platelet Response | Targeted therapeutic platelet response was defined as a (single) platelet count that was double the baseline level and between 50 and 450 × 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. | Baseline and after first dose (days 3, 5, 8, 10, 12, 15, and days 17 and 19 for participants dosed on day 22) and after second dose (days 17, 19, and 22 for participants dosed on day 15, and days 24, 26, 29, 32, 36, 43, 50, 64, and 78 in all participants) | 
| Number of Participants With an Increase in Platelet Count of ≥ 20 x 10⁹ Cells/L From Baseline | Platelet count data after the use of rescue medication were not included; participants with no platelet count data were considered non-responders. | Baseline and after first dose (days 3, 5, 8, 10, 12, 15, and days 17 and 19 for participants dosed on day 22) and after second dose (days 17, 19, and 22 for participants dosed on day 15, and days 24, 26, 29, 32, 36, 43, 50, 64, and 78 in all participants) | 
| Number of Participants With Peak Platelet Counts of ≥ 100 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 (days 3, 5, 8, 10, 12, 15, and days 17 and 19 for participants dosed on day 22), and after second dose (days 17, 19, and 22 for participants dosed on day 15, and days 24, 26, 29, 32, 36, 43, 50, 64, and 78 for all participants) | 
| Number of Participants With Peak Platelet Counts of ≥ 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 (days 3, 5, 8, 10, 12, 15, and days 17 and 19 for participants dosed on day 22), and after second dose (days 17, 19, and 22 for participants dosed on day 15, and days 24, 26, 29, 32, 36, 43, 50, 64, and 78 for all participants) | 
| Change From Baseline to Peak Platelet Level | Platelet count data after the use of rescue medication were not included. | Baseline and after first dose (days 3, 5, 8, 10, 12, 15, and days 17 and 19 for participants dosed on day 22) and after second dose (days 17, 19, and 22 for participants dosed on day 15, and days 24, 26, 29, 32, 36, 43, 50, 64, and 78 in all participants) | 
| Time to Peak Platelet Count | Time from the date of study drug administration (day 1, 15 or 22) to the day of peak platelet count after each dose. Platelet count data after the use of rescue medication were not included. | From first dose of study drug to day 15 or 22, and from the second dose of study drug (day 15 or 22) to day 78 | 
| Duration Within the Targeted Therapeutic Range | Targeted therapeutic platelet level was defined as a platelet count that was double the baseline level and between 50 and 450 × 10⁹ cells/L. Platelet count data after the use of rescue medication were not included. | From first dose of study drug to day 15 or 22, and from the second dose of study drug (day 15 or 22) to day 78 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune Thrombocytopenic Purpura, Idiopathic Thrombocytopenic Purpura, ITP, Thrombocytopenia