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

• Medical Standard of Care for ITP (Drug)
• Romiplostim (Biological), also known as AMG 531

Primary outcomes

• 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 outcomes

• 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.

Sex: All, ages: 18 Years to any

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

Participant flow

Outcome results

• Number of Participants With Splenectomy During 52-Week Treatment Period (Primary), Number, Participants: Standard of Care 28; Romiplostim 14 (p <0.0001)
• Number of Participants With Treatment Failure During 52-Week Treatment Period (Primary), Number, Participants: Standard of Care 23; Romiplostim 18 (p 0.0005)
• Time to Splenectomy (Secondary), Median, days: Standard of Care NA (NA to NA); Romiplostim NA (NA to NA)
• Percentage of Participants With Platelet Response (Secondary), Number, percentage of participants: Standard of Care 6.7; Romiplostim 3.9
• Change in ITP-PAQ Physical Health Domain of Symptoms (Secondary), Least squares mean, Units on a scale: Standard of Care 12.5 +/- 2.1; Romiplostim 16.0 +/- 1.9 (p 0.0133)
• Change in ITP-PAQ Physical Health Domain of Fatigue (Secondary), Least squares mean, Units on a scale: Standard of Care 9.5 +/- 3.2; Romiplostim 11.2 +/- 3.1 (p 0.3434)
• Change in ITP-PAQ Physical Health Domain of Bother (Secondary), Least squares mean, Units on a scale: Standard of Care 13.0 +/- 2.7; Romiplostim 16.8 +/- 2.5 (p 0.0076)
• Change in ITP-PAQ Physical Health Domain of Activity (Secondary), Least squares mean, Units on a scale: Standard of Care 8.2 +/- 3.7; Romiplostim 17.1 +/- 3.5 (p 0.0246)

Adverse events

Time frame: 52 week treatment period

Serious adverse events by term

34 more terms not shown.

Other adverse events by term

• Kuter DJ, Mathias SD, Rummel M, Mandanas R, Giagounidis AA, Wang X, Deuson RR. Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care. Am J Hematol. 2012 May;87(5):558-61. doi: 10.1002/ajh.23163. Epub 2012 Mar 28. PMID 22460421
• Kuter DJ, Rummel M, Boccia R, Macik BG, Pabinger I, Selleslag D, Rodeghiero F, Chong BH, Wang X, Berger DP. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010 Nov 11;363(20):1889-99. doi: 10.1056/NEJMoa1002625. PMID 21067381

• MD, Study director, Amgen