A Prospective, Phase IV, Open-Label, Multi-Center Study Evaluating Changes in Bone Marrow Morphology in Adult Subjects Receiving Romiplostim for the Treatment of Thrombocytopenia Associated with Immune (Idiopathic) Thrombocytopenia Purpura (ITP)

• Register: EUCTR
• Last refreshed on: 10 March 2014
• Main ID: EUCTR2008-004347-10-AT
• Date of registration: 06/05/2009
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: A Prospective, Phase IV, Open-Label, Multi-Center Study Evaluating Changes in Bone Marrow Morphology in Adult Subjects Receiving Romiplostim for the Treatment of Thrombocytopenia Associated with Immune (Idiopathic) Thrombocytopenia Purpura (ITP)
• Scientific title: A Prospective, Phase IV, Open-Label, Multi-Center Study Evaluating Changes in Bone Marrow Morphology in Adult Subjects Receiving Romiplostim for the Treatment of Thrombocytopenia Associated with Immune (Idiopathic) Thrombocytopenia Purpura (ITP)
• Date of first enrolment: 17/06/2009
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004347-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Austria, Belgium, Bulgaria, Czech Republic, Estonia, Germany, Hungary, Italy, Lithuania, Poland, Slovenia, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
Disease related
• Diagnosis of ITP according to American Society of Hematology (ASH) guidelines
• Subject must have had a bone marrow biopsy within one year prior to planned first
dose of romiplostim (with available bone marrow tissue block or unstained histological slides to send to a central laboratory for interpretation) or must consent
to a pre-treatment bone marrow biopsy within 3 weeks prior to planned first dose of
romiplostim. Central laboratory interpretation is required prior to first dose of romiplostim
• Subject must agree to a scheduled bone marrow biopsy at Year 1, Year 2, or Year
3 following romiplostim treatment and any unscheduled biopsies if clinically indicated
Demographic
• Subject > 18 years of age
Laboratory
• Baseline bone marrow reticulin grade of 0, 1, 2, or 3 according to the modified
Bauermeister grading scheme as assessed by central laboratory interpretation
• Platelet count < 50x 109/L
Medications
• Must have received at least 1 prior ITP therapy (examples of ITP therapy include
corticosteroids, IVIG, splenectomy)
Ethical
• Subject (or legally-acceptable representative) is willing and able to provide written
informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Disease Related
• Baseline bone marrow biopsy positive for collagen fibrosis
• Any known history of or currently active bone marrow stem cell disorder, hematological malignancy, myeloproliferative disorder, myelodysplastic syndrome
• Any current active malignancy
• Any prior exposure to cytostatic chemotherapy or radiotherapy for malignancy
• Subject has undergone pacemaker placement, cardiac ablation of arrhythmia, and/or any current treatment with Vaughan Williams Class IA – IC and Class III agents (Vaughan Williams, 1970)
Medications
• Subject has participated in any study evaluating PEG-rHuMGDF, recombinant
human thrombopoietin (rHuTPO), or thrombopoietin receptor agonists (ie romiplostim
or eltrombopag)
• Subject has a known hypersensitivity to any recombinant E coli-derived product
General
• Subject is currently enrolled in or has not yet completed (at least 4 weeks since
ending) other investigational device or drug trial(s) or subject is receiving other
investigational agent(s)
• Other investigational procedures are excluded
• Subject of child-bearing potential is evidently pregnant (eg positive pregnancy test)
or is breast feeding
• Subject is not using adequate contraceptive precautions
• 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
and/or is unable to comply with study procedures


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Thrombocytopenia associated with ITP
MedDRA version: 9.1 Level: LLT Classification code 10021245 Term: Idiopathic thrombocytopenic purpura

Intervention(s)

Trade Name: Nplate
Product Name: Romiplostim
Product Code: AMG 531
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Romiplostim
Current Sponsor code: AMG 531
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 500 deliverable-

Primary Outcome(s)

Primary end point(s): The primary endpoint is the incidence of collagen fibrosis as evidenced by trichrome staining at Years 1, 2, or 3 after initial romiplostim exposure using the modified Bauermeister grading scale.

Secondary Objective: To evaluate the presence of collagen fibrosis as evidenced by trichrome staining 12 weeks after romiplostim discontinuation in subjects who developed collagen fibrosis at Year 1, Year 2, or Year 3 after exposure of romiplostim.
To evaluate the incidence of increased reticulin fibrosis as evidenced by silver staining at Year 1, Year 2, or Year 3 after exposure of romiplostim.
To evaluate electrocardiogram (ECG) changes after exposure to romiplostim.
To evaluate the incidence of cytopenias (anemia or neutropenia) after exposure to romiplostim.
To evaluate the overall safety as evidenced by adverse events and the development of neutralizing antibodies to romiplostim or cross-reacting antibodies to endogenous
thrombopoietin.

Main Objective: The primary objective of this study is to evaluate the incidence of collagen fibrosis as
evidenced by trichrome staining at Year 1, Year 2, or Year 3 after initial exposure of romiplostim.

Secondary ID(s)

20080009