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

December 20, 2019 updated by: Amgen

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

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

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: Romiplostim 0.2 µg/kg
Participants received 0.2 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.
Administered by subcutaneous injection
Other Names:
  • AMG 531
  • NPLATE
Experimental: Part A: Romiplostim 0.5 µg/kg
Participants received 0.5 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.
Administered by subcutaneous injection
Other Names:
  • AMG 531
  • NPLATE
Experimental: Part A: Romiplostim 1.0 µg/kg
Participants received 1.0 µg/kg romiplostim subcutaneously on day 1 and on day 15 or 22 depending on platelet counts.
Administered by subcutaneous injection
Other Names:
  • AMG 531
  • NPLATE
Experimental: Part A: Romiplostim 3 µg/kg
Participants received 3.0 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.
Administered by subcutaneous injection
Other Names:
  • AMG 531
  • NPLATE
Experimental: Part A: Romiplostim 6 µg/kg
Participants received 6.0 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.
Administered by subcutaneous injection
Other Names:
  • AMG 531
  • NPLATE
Experimental: Part A: Romiplostim 10 µg/kg
Participants received 10.0 µg/kg romiplostim subcutaneously on day 1 and day 15 or 22, depending on platelet counts.
Administered by subcutaneous injection
Other Names:
  • AMG 531
  • NPLATE
Placebo Comparator: Part B: Placebo
Participants received placebo subcutaneously once a week for 6 weeks.
Administered by subcutaneous injection
Experimental: Part B: Romiplostim 1.0 µg/kg
Participants received 1.0 µg/kg subcutaneously once a week for 6 weeks.
Administered by subcutaneous injection
Other Names:
  • AMG 531
  • NPLATE
Experimental: Part B: Romiplostim 3.0 µg/kg
Participants received 3.0 µg/kg subcutaneously once a week for 6 weeks.
Administered by subcutaneous injection
Other Names:
  • AMG 531
  • NPLATE
Experimental: Part B: Romiplostim 6.0 µg/kg
Participants received 6.0 µg/kg subcutaneously once a week for 6 weeks.
Administered by subcutaneous injection
Other Names:
  • AMG 531
  • NPLATE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events
Time Frame: From first dose of study drug through 8 weeks (Part A) or 6 weeks (Part B) after last dose of study drug; 78 days
From first dose of study drug through 8 weeks (Part A) or 6 weeks (Part B) after last dose of study drug; 78 days
Number of Participants With Anti-romiplostim or Anti-endogenous Thrombopoietin Neutralizing Antibodies
Time Frame: Assessed on day 29 (Part A only), day 43 (Part B only), and day 78
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Achieved Targeted Therapeutic Platelet Level in Part A
Time Frame: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)

Targeted therapeutic platelet level was defined as a doubling of baseline platelet counts and between 50 to 450 x 10⁹ 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)
Number of Participants With an Increase in Platelet Count of ≥ 20 x 10⁹ Cells/L Over Baseline in Part A
Time Frame: After first dose (day 1 to day 15 or 22), and after second dose (day 15 or 22 to day 78)
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)
Number of Participants With a Peak Platelet Count ≥ 100 x 10⁹ Cells/L in Part A
Time Frame: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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)
Number of Participants With a Peak Platelet Count of > 450 x 10⁹ Cells/L in Part A
Time Frame: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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)
Peak Platelet Count After Each Dose in Part A
Time Frame: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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)
Change From Baseline in Peak Platelet Count After Each Dose in Part A
Time Frame: Baseline and after first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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)
Time to Peak Platelet Count After Each Dose in Part A
Time Frame: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)
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)
Duration Within the Targeted Therapeutic Platelet Range In Part A
Time Frame: After first dose (day 1 to day 15 or 22) and after second dose (day 15 or 22 to day 78)

Targeted therapeutic platelet level was defined as a platelet count that was double the baseline level and ≥ 50 and ≤ 450 × 10⁹ 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)
Percentage of Participants Who Achieved Targeted Therapeutic Platelet Level In Part B
Time Frame: Day 1 to day 78

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 10⁹ cells/L and less than or equal to 450 x 10⁹ cells/L.

Platelet count data after use of rescue medication were not included in the analysis.

Day 1 to day 78
Percentage of Participants With an Increase in Platelet Count of ≥ 20 x 10⁹ Cells/L Over Baseline in Part B
Time Frame: Day 1 to day 78
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
Percentage of Participants With a Peak Platelet Count of ≥ 100 x 10⁹ Cells/L in Part B
Time Frame: Day 1 to day 78
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
Percentage of Participants With a Peak Platelet Count of > 450 x 10⁹ Cells/L in Part B
Time Frame: Day 1 to day 78
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
Percentage of Participants With a Peak Platelet Count of > 500 x 10⁹ Cells/L in Part B
Time Frame: Day 1 to day 78
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
Peak Platelet Count in Part B
Time Frame: Day 1 to day 78
Platelet count data after administration of rescue medication were not included in the analysis.
Day 1 to day 78
Change From Baseline in Peak Platelet Count in Part B
Time Frame: Baseline and day 1 to day 78
Platelet count data after administration of rescue medication were not included in the analysis.
Baseline and day 1 to day 78
Time to Peak Platelet Count in Part B
Time Frame: Day 1 to day 78
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
Duration Within the Targeted Therapeutic Platelet Range in Part B
Time Frame: Day 1 to day 78

Targeted therapeutic platelet level was defined as a doubling of baseline platelet counts and within the range of greater than or equal to 50 × 10⁹ cells/L and less than or equal to 450 × 10⁹ cells/L.

Platelet count data after administration of rescue medication were not included in the analysis.

Day 1 to day 78

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2002

Primary Completion (Actual)

June 17, 2004

Study Completion (Actual)

June 17, 2004

Study Registration Dates

First Submitted

May 20, 2005

First Submitted That Met QC Criteria

May 20, 2005

First Posted (Estimate)

May 23, 2005

Study Record Updates

Last Update Posted (Actual)

January 10, 2020

Last Update Submitted That Met QC Criteria

December 20, 2019

Last Verified

December 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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