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

Idiopathic Thrombocytopenic Purpura Clinical Trial

Official title:

A Dose-finding Study Evaluating the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects With Immune Thrombocytopenic Purpura (ITP)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00111475
• Other study ID #: 20000137
• Status: Completed
• Phase: Phase 2
• Start date: July 1, 2002
• Est. completion date: June 17, 2004

Study information

• Verified date: December 2019
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: June 17, 2004
• Est. primary completion date: June 17, 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Idiopathic Thrombocytopenic Purpura
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic

Intervention

Drug:
• Romiplostim
Administered by subcutaneous injection
• Placebo
Administered by subcutaneous injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (2)

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. Erratum in: N Engl J Med. 2006 Nov 9;355(19):2054. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events		From first dose of study drug through 8 weeks (Part A) or 6 weeks (Part B) after last dose of study drug; 78 days
Primary	Number of Participants With Anti-romiplostim or Anti-endogenous Thrombopoietin Neutralizing Antibodies	The development of antibodies to romiplostim or to endogenous thrombopoietin (eTPO) was assessed using a neutralizing bioassay. Participants positive for neutralizing antibodies at any of the assessments during the study are reported.	Assessed on day 29 (Part A only), day 43 (Part B only), and day 78
Secondary	Number of Participants Who Achieved Targeted Therapeutic Platelet Level in Part A	Targeted therapeutic platelet level was defined as a doubling of baseline platelet counts and between 50 to 450 x 10? cells/L.; Platelet count data after the use of rescue medication were not included; participants with no platelet count data were considered non-responders.	After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
Secondary	Number of Participants With an Increase in Platelet Count of = 20 x 10? Cells/L Over Baseline in Part A	Platelet count data after the use of rescue medication were not included; participants with no platelet count data were considered non-responders.	After first dose (day 1 to day 15 or 22), and after second dose (day 15 or 22 to day 78)
Secondary	Number of Participants With a Peak Platelet Count = 100 x 10? Cells/L in Part A	Platelet count data after the use of rescue medication were not included; participants with no platelet count data were considered non-responders.	After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
Secondary	Number of Participants With a Peak Platelet Count of > 450 x 10? Cells/L in Part A	Platelet count data after the use of rescue medication were not included; participants with no platelet count data were considered non-responders.	After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
Secondary	Peak Platelet Count After Each Dose in Part A	Platelet count data after the use of rescue medication were not included.	After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
Secondary	Change From Baseline in Peak Platelet Count After Each Dose in Part A	Platelet count data after the use of rescue medication were not included.	Baseline and after first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
Secondary	Time to Peak Platelet Count After Each Dose in Part A	Platelet count data after the use of rescue medication were not included.	After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
Secondary	Duration Within the Targeted Therapeutic Platelet Range In Part A	Targeted therapeutic platelet level was defined as a platelet count that was double the baseline level and = 50 and = 450 × 10? cells/L.; Platelet count data after the use of rescue medication were not included.	After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
Secondary	Percentage of Participants Who Achieved Targeted Therapeutic Platelet Level In Part B	Targeted therapeutic platelet level was defined as a doubling of baseline platelet counts and within the range of greater than or equal to 50 x 10? cells/L and less than or equal to 450 x 10? cells/L.; Platelet count data after use of rescue medication were not included in the analysis.	Day 1 to day 78
Secondary	Percentage of Participants With an Increase in Platelet Count of = 20 x 10? Cells/L Over Baseline in Part B	Platelet count data after administration of rescue medication were not included in the analysis. Participants with no platelet count data were considered non-responders.	Day 1 to day 78
Secondary	Percentage of Participants With a Peak Platelet Count of = 100 x 10? Cells/L in Part B	Platelet count data after administration of rescue medication were not included in the analysis. Participants with no platelet count data were considered non-responders.	Day 1 to day 78
Secondary	Percentage of Participants With a Peak Platelet Count of > 450 x 10? Cells/L in Part B	Platelet count data after administration of rescue medication were not included in the analysis. Participants with no platelet count data were considered non-responders.	Day 1 to day 78
Secondary	Percentage of Participants With a Peak Platelet Count of > 500 x 10? Cells/L in Part B	Platelet count data after administration of rescue medication were not included in the analysis. Participants with no platelet count data were considered non-responders.	Day 1 to day 78
Secondary	Peak Platelet Count in Part B	Platelet count data after administration of rescue medication were not included in the analysis.	Day 1 to day 78
Secondary	Change From Baseline in Peak Platelet Count in Part B	Platelet count data after administration of rescue medication were not included in the analysis.	Baseline and day 1 to day 78
Secondary	Time to Peak Platelet Count in Part B	Platelet count data after administration of rescue medication were not included in the analysis. Time to peak platelet count was analyzed using the Kaplan-Meier method.	Day 1 to day 78
Secondary	Duration Within the Targeted Therapeutic Platelet Range in Part B	Targeted therapeutic platelet level was defined as a doubling of baseline platelet counts and within the range of greater than or equal to 50 × 10? cells/L and less than or equal to 450 × 10? cells/L.; Platelet count data after administration of rescue medication were not included in the analysis.	Day 1 to day 78

External Links

•   AmgenTrials clinical trials website
•   FDA-approved Drug Labeling
•   Notice regarding posted summaries of trial results
•   To access clinical trial results information click on this link