A Prospective, Study Evaluating Changes in Bone Marrow Morphology in Adult Subjects Receiving Romiplostim for the Treatment of Thrombocytopenia Associated With Immune (Idiopathic) Thrombocytopenia Purpura (ITP) - Full Text View

Sponsor:	Amgen
Information provided by:	Amgen
ClinicalTrials.gov Identifier:	NCT00907478

Purpose

This is a prospective, phase IV, multi-center, open label, study evaluating the changes in bone marrow reticulin and collagen in adult subjects receiving romiplostim for the treatment of thrombocytopenia associated with ITP.

The purpose of this study is to evaluate changes in bone marrow morphology (structure) after long-term exposure to romiplostim.

Subjects, diagnosed with ITP according to the ASH Guidelines, will be sequentially enrolled into the following groups:

Bone marrow biopsy at baseline and Year 1
Bone marrow biopsy at baseline and Year 2
Bone marrow biopsy at baseline and Year 3

All subjects will receive romiplostim for 3 years, unless withdrawn from the study early. All subjects will return for 1 visit post treatment for End of Study (EOS) procedures.

Condition	Intervention	Phase
Thrombocytopenia Idiopathic Thrombocytopenic Purpura	Biological: romiplostim	Phase 4

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:

Genetics Home Reference related topics: hemophilia MYH9-related disorder thrombotic thrombocytopenic purpura

Drug Information available for: Romiplostim

U.S. FDA Resources

Further study details as provided by Amgen:

Primary Outcome Measures:

The incidence of collagen fibrosis as evidenced by trichrome staining [ Time Frame: At Years 1, 2 or 3 after initial exposure of romiplostim ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

The incidence of clinically relevant changes in QT/QTc intervals, as defined as an absolute QTc interval > 500 ms or a QTc interval increase from baseline ≥ 60 ms post romiplostim exposure [ Time Frame: from Week 3 through End of Study (maximum total time is approximately 3 years + 3 months) ] [ Designated as safety issue: Yes ]
The incidence of any improvement of reticulin to a grade of ≤ 2 for subjects who developed grade 3 reticulin after initial exposure to romiplostim as measured by the modified Bauermeister grading scale [ Time Frame: At Year 1, Year 2, or Year 3 post romiplostim exposure ] [ Designated as safety issue: Yes ]
The incidence of CTCAE grade ≥ 2 shift in anemia or neutropenia post romiplostim exposure [ Time Frame: from Screening through End of Study (maximum total time estimated to be approximately 3 years + 3 months) ] [ Designated as safety issue: Yes ]
The incidence and severity of all adverse events including clinically significant changes in laboratory values [ Time Frame: from Screening through End of Study (maximum total time estimated to be approximately 3 years + 3 months) ] [ Designated as safety issue: Yes ]
To investigate any changes between each sampling of four cytokines (TGF- β1, PDGF, OPG and bFGF), and any correlation of these changes with bone marrow biopsies, clinical and laboratory findings [ Time Frame: At Week 12 and at Year 1, Year 2, or Year 3 of romiplostim exposure ] [ Designated as safety issue: Yes ]
The incidence of neutralizing antibody formation to romiplostim or cross-reacting antibodies to endogenous thrombopoietin [ Time Frame: from Screening through End of Study (maximum total time estimated to be approximately 3 years + 3 months) ] [ Designated as safety issue: Yes ]
The incidence of collagen fibrosis as evidenced by trichrome staining in subjects who developed collagen fibrosis at Yrs 1, 2, or 3 after initial exposure of romiplostim using modified Bauermeister grading scale [ Time Frame: 12 wks after romiplostim discontinuation ] [ Designated as safety issue: Yes ]
The incidence of bone marrow reticulin increases by ≥ 2 severity grades or increase to grade 4 over baseline as evidenced by reticulin silver staining using the modified Bauermeister grading scale [ Time Frame: At Year 1, Year 2, or Year 3 post romiplostim exposure ] [ Designated as safety issue: Yes ]

Enrollment:	169
Study Start Date:	August 2009
Estimated Study Completion Date:	January 2015
Estimated Primary Completion Date:	January 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Year 2 Bone Marrow Biopsy at baseline and Year 2	Biological: romiplostim Romiplostim will be administered weekly by SC injection for 3 years at a starting dose of 1 mcg/kg.
Experimental: Year 3 Bone Marrow Biopsy at baseline and Year 3	Biological: romiplostim Romiplostim will be administered weekly by SC injection for 3 years at a starting dose of 1 mcg/kg.
Experimental: Year 1 Bone Marrow Biopsy at baseline and Year 1	Biological: romiplostim Romiplostim will be administered weekly by SC injection for 3 years at a starting dose of 1 mcg/kg.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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
Subject ≥18 years of age
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 < 50 x 10^9/L
Must have received at least 1 prior ITP therapy (examples of ITP therapy include corticosteroids, IVIG, splenectomy)
Subject (or legally-acceptable representative) is willing and able to provide written informed consent

Exclusion Criteria:

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)
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
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00907478

Sponsors and Collaborators

Amgen

Investigators

Study Director:

MD

Amgen

More Information

Additional Information:

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Global Development Leader, Amgen Inc.
ClinicalTrials.gov Identifier:	NCT00907478 History of Changes
Other Study ID Numbers:	20080009
Study First Received:	May 21, 2009
Last Updated:	January 20, 2011
Health Authority:	Australia: Therapeutic Goods Administration Austria: AGES - PharmaMed Austria Institut Wissenschaft & Information Austria: Bundesamt fur Sicherheit im Gesundheitswesen Austria: Bundesamt für Sicherheit im Gesundheitswesen Belgium: Ministry of Health Bulgaria: Bulgarian Drug Agency Canada: Health Canada Canada: Health Products and Food Branch Czech Republic: State Institute for Drug Control Estonia: State Agency of Medicines European Union: European Medicines Agency Germany: Federal Institute for Drugs and Medical Devices Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe Hungary: National Institute of Pharmacy Italy: Ministry of Health Lithuania: State Medicines Control Agency of Lithuania Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Romaina: National Medicines Agency Russia: Federal Service for Surveillance in the field of Healthcare and Social Development (a body of the Ministry of Health) Russia: Ministry of Health Slovakia: State Institiute for Drug Control Slovenia: Agency for Medicinal Products and Medicinal Devices of the Republic of Slovenia (ARSZMP) Spain: Agencia Española de Medicamentos y Productos Sanitarios Sweden: Lakemedelsverket United States: Food and Drug Administration

Keywords provided by Amgen:

Idiopathic Thrombocytopenic Purpura
ITP

Additional relevant MeSH terms:

Purpura
Purpura, Thrombocytopenic
Thrombocytopenia
Purpura, Thrombocytopenic, Idiopathic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes

Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Blood Platelet Disorders
Immune System Diseases
Hemorrhagic Disorders
Autoimmune Diseases

ClinicalTrials.gov processed this record on May 24, 2012