Evaluating the Safety and Efficacy of Romiplostim (AMG 531) in Thrombocytopenic Subjects With Immune Thrombocytopenic Purpura (ITP)

Amgen

Status and phase: Completed; Phase 2

Conditions: Idiopathic Thrombocytopenic Purpura

Treatments: Drug: Placebo; Drug: Romiplostim

Study type: Interventional

Funder types: Industry

Identifiers

NCT00111475

20000137

Details and patient eligibility

About

The primary objective of this study is to evaluate the safety and tolerability of romiplostim in thrombocytopenic patients with ITP.

Enrollment: 45 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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45 participants in 10 patient groups, including a placebo group

Part A: Romiplostim 0.2 µg/kg

Experimental group

Description:

Participants received 0.2 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.

Treatment:

Drug: Romiplostim

Part A: Romiplostim 0.5 µg/kg

Experimental group

Description:

Participants received 0.5 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.

Treatment:

Drug: Romiplostim

Part A: Romiplostim 1.0 µg/kg

Experimental group

Description:

Participants received 1.0 µg/kg romiplostim subcutaneously on day 1 and on day 15 or 22 depending on platelet counts.

Treatment:

Drug: Romiplostim

Part A: Romiplostim 3 µg/kg

Experimental group

Description:

Participants received 3.0 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.

Treatment:

Drug: Romiplostim

Part A: Romiplostim 6 µg/kg

Experimental group

Description:

Participants received 6.0 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.

Treatment:

Drug: Romiplostim

Part A: Romiplostim 10 µg/kg

Experimental group

Description:

Participants received 10.0 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.

Treatment:

Drug: Romiplostim

Part B: Placebo

Placebo Comparator group

Description:

Participants received placebo subcutaneously once a week for 6 weeks.

Treatment:

Drug: Placebo

Part B: Romiplostim 1.0 µg/kg

Experimental group

Description:

Participants received 1.0 µg/kg subcutaneously once a week for 6 weeks.

Treatment:

Drug: Romiplostim

Part B: Romiplostim 3.0 µg/kg

Experimental group

Description:

Participants received 3.0 µg/kg subcutaneously once a week for 6 weeks.

Treatment:

Drug: Romiplostim

Part B: Romiplostim 6.0 µg/kg

Experimental group

Description:

Participants received 6.0 µg/kg subcutaneously once a week for 6 weeks.

Treatment:

Drug: Romiplostim