Clinical trial NCT00111475: Evaluating the Safety and Efficacy of Romiplostim (AMG 531) in Thrombocytopenic Subjects With Immune Thrombocytopenic Purpura (ITP)
Official title: A Dose-finding Study Evaluating the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects With Immune Thrombocytopenic Purpura (ITP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Thrombocytopenic Purpura
Keywords: Immune Thrombocytopenic Purpura
Idiopathic Thrombocytopenic Purpura
Thrombocytopenic
Thrombocytopenia
ITP
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2005-05-23
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part A was a sequential cohort dose escalation study. Part B was a randomized, placebo-controlled parallel group study.
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From first dose of study drug through 8 weeks (Part A) or 6 weeks (Part B) after last dose of study drug; 78 days
measure: Number of Participants With Anti-romiplostim or Anti-endogenous Thrombopoietin Neutralizing Antibodies
timeFrame: Assessed on day 29 (Part A only), day 43 (Part B only), and day 78
Secondary outcomes:
measure: Number of Participants Who Achieved Targeted Therapeutic Platelet Level in Part A
timeFrame: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
measure: Number of Participants With an Increase in Platelet Count of ≥ 20 x 10⁹ Cells/L Over Baseline in Part A
timeFrame: After first dose (day 1 to day 15 or 22), and after second dose (day 15 or 22 to day 78)
measure: Number of Participants With a Peak Platelet Count ≥ 100 x 10⁹ Cells/L in Part A
timeFrame: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
measure: Number of Participants With a Peak Platelet Count of > 450 x 10⁹ Cells/L in Part A
timeFrame: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
measure: Peak Platelet Count After Each Dose in Part A
timeFrame: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
measure: Change From Baseline in Peak Platelet Count After Each Dose in Part A
timeFrame: Baseline and after first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
measure: Time to Peak Platelet Count After Each Dose in Part A
timeFrame: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
measure: Duration Within the Targeted Therapeutic Platelet Range In Part A
timeFrame: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
measure: Percentage of Participants Who Achieved Targeted Therapeutic Platelet Level In Part B
timeFrame: Day 1 to day 78
measure: Percentage of Participants With an Increase in Platelet Count of ≥ 20 x 10⁹ Cells/L Over Baseline in Part B
timeFrame: Day 1 to day 78
measure: Percentage of Participants With a Peak Platelet Count of ≥ 100 x 10⁹ Cells/L in Part B
timeFrame: Day 1 to day 78
measure: Percentage of Participants With a Peak Platelet Count of > 450 x 10⁹ Cells/L in Part B
timeFrame: Day 1 to day 78
measure: Percentage of Participants With a Peak Platelet Count of > 500 x 10⁹ Cells/L in Part B
timeFrame: Day 1 to day 78
measure: Peak Platelet Count in Part B
timeFrame: Day 1 to day 78
measure: Change From Baseline in Peak Platelet Count in Part B
timeFrame: Baseline and day 1 to day 78
measure: Time to Peak Platelet Count in Part B
timeFrame: Day 1 to day 78
measure: Duration Within the Targeted Therapeutic Platelet Range in Part B
timeFrame: Day 1 to day 78
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Cines DB, Wasser J, Rodeghiero F, Chong BH, Steurer M, Provan D, Lyons R, Garcia-Chavez J, Carpenter N, Wang X, Eisen M. Safety and efficacy of romiplostim in splenectomized and nonsplenectomized patients with primary immune thrombocytopenia. Haematologica. 2017 Aug;102(8):1342-1351. doi: 10.3324/haematol.2016.161968. Epub 2017 Apr 14.
citation: Bussel JB, Kuter DJ, George JN, McMillan R, Aledort LM, Conklin GT, Lichtin AE, Lyons RM, Nieva J, Wasser JS, Wiznitzer I, Kelly R, Chen CF, Nichol JL. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med. 2006 Oct 19;355(16):1672-81. doi: 10.1056/NEJMoa054626.