Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura

Study Overview
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Brief Summary
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This is a phase 3b, multi-center, randomized, Standard of Care (SOC)-controlled, open-label, 52-week treatment study to compare romiplostim to medical SOC for Idiopathic Thrombocytopenia Purpura (ITP), with a 6-month Safety Follow-up. Patients randomized to romiplostim must complete the taper or discontinuation of medical SOC for ITP as soon as medically feasible after the initiation of romiplostim. After the completion or discontinuation of the study treatment period, any participant who does not transfer in to another romiplostim study will complete a 6-month Safety Follow-up period.

Official Title
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A Randomized, Controlled, Open-label Study Evaluating the Efficacy and Tolerability of AMG 531 Versus Medical Standard of Care as Chronic Therapy for Non-splenectomized Subjects With Immune (Idiopathic) Thrombocytopenic Purpura

Conditions
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Idiopathic Thrombocytopenic Purpura, Thrombocytopenia, Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP), Thrombocytopenic Purpura

Intervention / Treatment
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* Drug: Medical Standard of Care for ITP
* Biological: Romiplostim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥ 18 years of age Subject has a diagnosis of Idiopathic Thrombocytopenia Purpura (ITP) according to the American Society of Hematology (ASH) guidelines If subject is > 60 years of age, subject has a written bone marrow biopsy report confirming the diagnosis of ITP Subject has received at least 1 prior therapy for ITP Subject has a platelet count < 50,000 or their platelet count falls to < 50,000 during or after a clinically-indicated taper or discontinuation of current ITP therapy Before any study-specific procedure, the appropriate written informed consent must be obtained Exclusion Criteria: Subject has had a splenectomy for any reason Subject has an active malignancy Subject has a history of cancer, other than basal cell carcinoma or cervical carcinoma in situ, with treatment or active disease within 5 years Subject has a known history of bone marrow stem cell disorder Subject has participated in any study evaluating polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), recombinant human thrombopoietin (rHuTPO), AMG 531, or a thrombopoietic protein Subject is receiving other investigational agents or procedures Subject is currently enrolled in, or has completed within the last 30 days, another investigational device or drug study Subject is pregnant or breast feeding Subject is not using adequate contraceptive precautions Subject has known sensitivity to any recombinant E. coli-derived product Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and does not have a legally acceptable representative Subject has any kind of disorder that compromises the ability of the subject to comply with study procedures

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romiplostim<br>Romiplostim administered by subcutaneous injection once weekly at a starting dose of 3 μg/kg, adjusted to a maximum dose of 10 μg/kg to maintain a platelet count between 50 and 200 x 10^9/L for up to 52 weeks. | Biological: Romiplostim<br> <br> * Other names: AMG 531;|
| Other: Standard of Care<br>Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks. | Drug: Medical Standard of Care for ITP<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Splenectomy During 52-Week Treatment Period | Occurrence of a splenectomy. Participants who discontinued study during the treatment period prior to reporting a splenectomy were considered as having had a splenectomy. | 52 weeks | 
| Number of Participants With Treatment Failure During 52-Week Treatment Period | Treatment failure was defined by platelet counts ≤ 20 x 10^9/L for 4 consecutive weeks at the highest recommended dose and schedule, a major bleeding event, or change in therapy due to an intolerable side effect or bleeding symptom. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Splenectomy | Time to splenectomy in days calculated from date of randomization to date of splenectomy, or censored at date of end of treatment visit if no splenectomy was done during treatment period. | 52 weeks | 
| Percentage of Participants With Platelet Response | Platelet response was defined as platelet counts > 50 x 10^9/L, measured at each study visit (excluding those within 8 weeks of prior rescue medication use) up to the time of splenectomy or the end of initial treatment period, whichever occurred first. | Weeks 1-8, and Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Change in ITP-PAQ Physical Health Domain of Symptoms | Change from Baseline in the Immune Thrombocytopenic Purpura (ITP) Patient Assessment Questionnaire (PAQ) physical health domain of symptoms. This domain has a range of 0 to 100, with higher scores indicating a better health-related quality of life. Model included fixed effects of baseline assessment, geographic region, treatment group, assessment week, splenectomy status and treatment group-by-assessment week interaction. Treatment group and splenectomy status are time-varying covariates. | Baseline and 52 weeks | 
| Change in ITP-PAQ Physical Health Domain of Fatigue | Change from Baseline in the Immune Thrombocytopenic Purpura (ITP) Patient Assessment Questionnaire (PAQ) physical health domain of fatigue. This domain has a range of 0 to 100, with higher scores indicating a better health-related quality of life. Model included fixed effects of baseline assessment, geographic region, treatment group, assessment week, splenectomy status and treatment group-by-assessment week interaction. Treatment group and splenectomy status are time-varying covariates. | Baseline and 52 weeks | 
| Change in ITP-PAQ Physical Health Domain of Bother | Change from Baseline in the Immune Thrombocytopenic Purpura (ITP) Patient Assessment Questionnaire (PAQ) physical health domain of bother. This domain has a range of 0 to 100, with higher scores indicating a better health-related quality of life. Model included fixed effects of baseline assessment, geographic region, treatment group, assessment week, splenectomy status and treatment group-by-assessment week interaction. Treatment group and splenectomy status are time-varying covariates. | Baseline and 52 weeks | 
| Change in ITP-PAQ Physical Health Domain of Activity | Change from Baseline in the Immune Thrombocytopenic Purpura (ITP) Patient Assessment Questionnaire (PAQ) physical health domain of activity. This domain has a range of 0 to 100, with higher scores indicating a better health-related quality of life. Model included fixed effects of baseline assessment, geographic region, treatment group, assessment week, splenectomy status and treatment group-by-assessment week interaction. Treatment group and splenectomy status are time-varying covariates. | Baseline and 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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splenectomy, platelet, AMG 531, thrombopoietin, blood disorder, bleeding disorder, immune thrombocytopenic purpura, idiopathic thrombocytopenic purpura, immune (idiopathic) thrombocytopenic purpura, TPO, thrombopoietic protein