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

Phase 3

Completed

• Conditions: Thrombocytopenia; Idiopathic Thrombocytopenic Purpura; Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenic Purpura
• Interventions: Biological: Romiplostim; Drug: Medical Standard of Care for ITP

• Registration Number: NCT00415532
• Lead Sponsor: Amgen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-12-01
• Study First Submitted: 2006-12-21
• Study First Submitted QC: 2006-12-21
• Study First Posted: 2006-12-25
• Primary Completion: 2008-11-07
• Study Completion: 2009-05-11
• Results First Submitted: 2010-10-01
• Results First Submitted QC: 2013-05-31
• Results First Posted: 2013-07-08
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-04
• Last Update Posted: 2022-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 234

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Romiplostim	Romiplostim	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.
Standard of Care	Medical Standard of Care for ITP	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Splenectomy During 52-Week Treatment Period	52 weeks	Occurrence of a splenectomy. Participants who discontinued study during the treatment period prior to reporting a splenectomy were considered as having had a splenectomy.
Number of Participants With Treatment Failure During 52-Week Treatment Period	52 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Time to Splenectomy	52 weeks	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.
Percentage of Participants With Platelet Response	Weeks 1-8, and Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52	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.
Change in ITP-PAQ Physical Health Domain of Symptoms	Baseline and 52 weeks	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.
Change in ITP-PAQ Physical Health Domain of Fatigue	Baseline and 52 weeks	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.
Change in ITP-PAQ Physical Health Domain of Bother	Baseline and 52 weeks	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.
Change in ITP-PAQ Physical Health Domain of Activity	Baseline and 52 weeks	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.