- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02279173
Long-term Study of Romiplostim in Thrombocytopenic Pediatric Patients With Immune Thrombocytopenia (ITP)
A Single Arm, Open-label, Long-term Efficacy and Safety Study of Romiplostim in Thrombocytopenic Pediatric Subjects With Immune Thrombocytopenia (ITP)
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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New South Wales
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Randwick, New South Wales, Australia, 2031
- Research Site
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Queensland
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South Brisbane, Queensland, Australia, 4101
- Research Site
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Victoria
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Parkville, Victoria, Australia, 3052
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Brussels, Belgium, 1020
- Research Site
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Bruxelles, Belgium, 1200
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Gent, Belgium, 9000
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Leuven, Belgium, 3000
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Liege, Belgium, 4000
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Pará
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Belem, Pará, Brazil, 66033-000
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São Paulo
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Jau, São Paulo, Brazil, 17210-120
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Sao Paulo, São Paulo, Brazil, 05403-000
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Sao Paulo, São Paulo, Brazil, 08270-070
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Ontario
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Hamilton, Ontario, Canada, L8S 4K1
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Toronto, Ontario, Canada, M5G 1X8
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Quebec
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Montreal, Quebec, Canada, H4A 3J1
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Montreal, Quebec, Canada, H3T 1C5
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Olomouc, Czechia, 775 20
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Ostrava-Poruba, Czechia, 708 52
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Praha 5, Czechia, 150 06
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Montpellier cedex 05, France, 34295
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Nice Cedex 3, France, 06202
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Paris, France, 75019
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Vandoeuvre les Nancy, France, 54511
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Budapest, Hungary, 1094
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Debrecen, Hungary, 4032
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Szeged, Hungary, 6720
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Beer Sheva, Israel, 84101
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Haifa, Israel, 31096
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Jerusalem, Israel, 91120
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Petach Tikvah, Israel, 49202
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Tel Aviv, Israel, 64239
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Tel Hashomer, Israel, 52621
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Nuevo León
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Monterrey, Nuevo León, Mexico, 64460
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Bydgoszcz, Poland, 85-094
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Lodz, Poland, 91-738
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Olsztyn, Poland, 10-561
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Zabrze, Poland, 41-800
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Krasnodar, Russian Federation, 350007
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Moscow, Russian Federation, 117997
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Moscow, Russian Federation, 117198
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Saint-Petersburg, Russian Federation, 197022
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Saratov, Russian Federation, 410028
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Volgograd, Russian Federation, 400138
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Gauteng
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Johannesburg, Gauteng, South Africa, 2013
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Parktown, Gauteng, South Africa, 2193
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KwaZulu-Natal
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Durban, KwaZulu-Natal, South Africa, 4001
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Western Cape
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Tygerberg, Western Cape, South Africa, 7505
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Madrid, Spain, 28046
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Madrid, Spain, 28009
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Cataluña
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Barcelona, Cataluña, Spain, 08035
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Esplugues de Llobregat, Cataluña, Spain, 08950
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Comunidad Valenciana
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Valencia, Comunidad Valenciana, Spain, 46026
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Basel, Switzerland, 4056
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St. Gallen, Switzerland, 9006
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Zuerich, Switzerland, 8032
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Adana, Turkey, 01130
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Antalya, Turkey, 07059
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Izmir, Turkey, 35100
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Birmingham, United Kingdom, B4 6NH
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Edinburgh, United Kingdom, EH9 1LF
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London, United Kingdom, W12 0HS
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Manchester, United Kingdom, M13 9WL
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California
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Roseville, California, United States, 95661
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Georgia
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Atlanta, Georgia, United States, 30322
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Illinois
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Chicago, Illinois, United States, 60611
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Peoria, Illinois, United States, 61615
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Indiana
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Indianapolis, Indiana, United States, 46260
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Iowa
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Iowa City, Iowa, United States, 52242
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Missouri
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Kansas City, Missouri, United States, 64108
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Nevada
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Las Vegas, Nevada, United States, 89109
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New York
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New York, New York, United States, 10021
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Ohio
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Cincinnati, Ohio, United States, 45229
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Columbus, Ohio, United States, 43205
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15224
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Tennessee
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Nashville, Tennessee, United States, 37232
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Texas
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Dallas, Texas, United States, 75390
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Fort Worth, Texas, United States, 76104
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Houston, Texas, United States, 77030
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of primary ITP according to The American Society of Hematology (ASH) Guidelines at least 6 months before screening, regardless of splenectomy status
- Age ≥ 1 year and < 18 years of age
- Refractory to prior ITP therapy, relapsed after at prior ITP therapy, or be ineligible for other therapies. Examples of prior therapy include: corticosteroids, intravenous Immunoglobulin (IVIG), anti-D immunoglobulin, platelet transfusions.
- Platelet count ≤ 30 x10^9/L or is experiencing uncontrolled bleeding
- Has provided informed consent before any study-specific procedure;
Adequate hematologic, renal, and liver function during screening:
- Hemoglobin > 10.0 g/dL
- Serum creatinine ≤ 1.5 x the upper limit of normal (ULN)
- Total serum bilirubin ≤ 1.5 x the ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x the ULN
- For the EU, Switzerland and Turkey protocol supplement, subject must agree to a scheduled bone marrow biopsy and aspirate at Year 1 or Year 2 following romiplostim treatment and any unscheduled biopsies if clinically indicated
- For the EU, Switzerland and Turkey protocol supplement, a reticulin grade of 0, 1, 2, or 3 according to the modified Bauermeister grading scale, as assessed by central laboratory from a bone marrow biopsy performed within 1 year prior to planned first dose of romiplostim or consent to a pre-treatment bone marrow biopsy and aspirate prior to planned first dose of romiplostim
Exclusion Criteria:
- History of a bone marrow stem cell disorder (Any abnormal bone marrow findings other than those typical of ITP must be approved by Amgen before a subject may be enrolled)
- Prior bone marrow transplant or peripheral blood progenitor cell transplant
- Active or prior malignancy except non-melanoma skin cancers within the last 5 years
- History of myelodysplastic syndrome
- History of bleeding diathesis
- History of congenital thrombocytopenia
- History of Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV)
- History of systemic lupus erythematosus, Evans syndrome, or autoimmune neutropenia
- History of antiphospholipid antibody syndrome or known positive for lupus anticoagulant
- History of disseminated intravascular coagulation, hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura
- History of venous thromboembolism or thrombotic events
- Previous use of romiplostim or previous use of eltrombopag within 4 weeks of enrollment
- Previous use of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), recombinant human thrombopoietin (rHuTPO) or any other platelet producing agent
- Rituximab (for any indication) or 6-mercaptopurine within 8 weeks of enrollment, or anticipated use at any time during the study
- Splenectomy within 4 weeks of the screening visit
- Alkylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study
- Vaccinations known to decrease platelet counts within 8 weeks before the screening visit
- Currently enrolled in another investigational device or drug study, or less than 30 days since ending investigational study
- Will have investigational procedures while enrolled on study
- Female subject of child bearing potential (defined as having first menses) not willing to use, in combination with her partner highly effective methods of birth control during treatment and for 1 month after the end of treatment
- Subject is pregnant or breast feeding, or might become pregnant within 1 month after the end of treatment
- Subject has known hypersensitivity to any recombinant Escherichia coli derived product (eg, Infergen®, Neupogen®, somatropin, and Actimmune®)
- Has previously enrolled into this study
- Will not be available for protocol-required study visits or procedures, to the best of the subject's and investigator's knowledge
- Any kind of disorder that, may compromise the subject to give written informed consent and/or to comply with all required study procedures
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Romiplostim
Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years.
The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.
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Romiplostim subcutaneous weekly injection
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of Time With a Platelet Response During the First 6 Months of Treatment
Time Frame: Week 2 to Month 6, platelet response was assessed every week.
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Platelet response was defined as a platelet count of ≥ 50 x 10⁹/L with no rescue medication use for ITP in the past 4 weeks. Monthly platelet response was calculated based on the median platelet count during each month. For each participant, the percentage of time with platelet response during the first 6 months was calculated as the number of months a platelet response was observed divided by the total number of months response was assessed. |
Week 2 to Month 6, platelet response was assessed every week.
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Percentage of Participants Who Developed Collagen After Exposure to Romiplostim
Time Frame: Year 1 (Cohort 1) and year 2 (Cohort 2)
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The percentage of participants who developed collagen as evidenced by trichrome staining, defined as a Grade 4 on the modified Bauermeister grading scale: Grade 0: No reticulin fibers demonstrable Grade 1: Occasional fine individual fibers and foci of a fine fiber network Grade 2: Fine fiber network throughout most of the section; no coarse fibers Grade 3: Diffuse fiber network with scattered thick coarse fibers but no mature collagen (negative to trichrome staining) Grade 4: Diffuse, often course fiber network with areas of collagenization (positive trichrome staining) |
Year 1 (Cohort 1) and year 2 (Cohort 2)
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Percentage of Participants With Increased Modified Bauermeister Grade
Time Frame: Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)
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The percentage of participants with an increased modified Bauermeister grade defined as an increase by ≥ 2 severity grades or an increase to grade 4 (i.e., grade 0 to 2-4, grade 1 to 3-4, grade 2 to 4, or grade 3 to 4 over baseline). The modified Bauermeister grading scale: Grade 0: No reticulin fibers demonstrable Grade 1: Occasional fine individual fibers and foci of a fine fiber network Grade 2: Fine fiber network throughout most of the section; no coarse fibers Grade 3: Diffuse fiber network with scattered thick coarse fibers but no mature collagen (negative to trichrome staining) Grade 4: Diffuse, often course fiber network with areas of collagenization (positive trichrome staining) Participants without an evaluable baseline result were assumed to have a baseline modified Bauermeister score of 0. |
Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)
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Percentage of Participants Who Developed Bone Marrow Abnormalities
Time Frame: Year 1 (Cohort 1) and year 2 (Cohort 2)
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The percentage of participants with bone marrow abnormalities (eg, myelodysplastic syndrome, monosomy 7) based on analysis of bone marrow biopsy and aspirate samples using cytogenetics and fluorescence in situ hybridization.
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Year 1 (Cohort 1) and year 2 (Cohort 2)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of Time With a Platelet Response During the Overall Treatment Period
Time Frame: From week 2 to the end of the treatment period, 36 months
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Platelet response was defined as a platelet count of ≥ 50 x 10⁹/L with no rescue medication use in the past 4 weeks. Monthly platelet response was calculated based on the median platelet count during each month. For each participant, the percentage of time with platelet response was calculated as the number of months a platelet response was observed divided by the total number of months response was assessed. |
From week 2 to the end of the treatment period, 36 months
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Percentage of Time With an Increase in Platelet Count ≥ 20 x 10⁹ Cells/L Above Baseline
Time Frame: Baseline and from week 2 to month 36
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The percentage of time with an increase in platelet count ≥ 20 x 10⁹ cells/L above baseline from week 2 until the end of the treatment period without rescue medication use within the past 4 weeks. For each participant, the percentage of time with an increase in platelet count ≥ 20 x10⁹ cells/L above baseline was calculated as the number of months the median platelet count was ≥ 20 x10⁹ cells/L above baseline divided by the total number of months assessed. |
Baseline and from week 2 to month 36
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Number of Participants Reporting Use of Rescue Medications for ITP During the Treatment Period
Time Frame: From first dose of romiplostim to the end of the treatment period, 36 months
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Rescue medication is defined as any medication or transfusion, other than romiplostim and excluded medications, that is administered after enrollment to the participant with the intent of raising platelet counts or to prevent bleeding and includes concomitant medications for ITP in which the dose and/or schedule was increased. Permitted rescue medications included the following:
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From first dose of romiplostim to the end of the treatment period, 36 months
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Number of Participants Who Developed Anti-Romiplostim or Anti-Thrombopoietin Neutralizing Antibodies
Time Frame: Week 12, week 52 and every 24 weeks thereafter up to month 36
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Blood samples were first tested for the presence of binding antibodies to romiplostim or the peptide portion of romiplostim, and to endogenous thrombopoietin (eTPO). Samples testing positive for binding antibodies were then tested for neutralizing antibodies by assessing their ability to neutralize romiplostim and/or eTPO in a cell-based bioassay. Participants who developed neutralizing antibodies are those who had a postbaseline positive result with a negative or no result at baseline. Transient is defined as a negative result at the participant's last time point tested within the study period. |
Week 12, week 52 and every 24 weeks thereafter up to month 36
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Number of Participants With Adverse Events
Time Frame: SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months).
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An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant, which does not necessarily have a causal relationship with study treatment. A serious adverse event (SAE) was defined as an AE that met at least 1 of the following criteria:
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SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months).
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Percentage of Participants Who Developed Increased Reticulin
Time Frame: Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)
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The percentage of participants with increased reticulin as evidenced by silver staining and defined as any increase from baseline in the modified Bauermeister grade: Grade 0: No reticulin fibers demonstrable Grade 1: Occasional fine individual fibers and foci of a fine fiber network Grade 2: Fine fiber network throughout most of the section; no coarse fibers Grade 3: Diffuse fiber network with scattered thick coarse fibers but no mature collagen (negative to trichrome staining) Grade 4: Diffuse, often course fiber network with areas of collagenization (positive trichrome staining) Participants without an evaluable baseline result were assumed to have a baseline modified Bauermeister score of 0. |
Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Tarantino MD, Despotovic J, Roy J, Grainger J, Cooper N, Beam D, Raj A, Maschan A, Kim J, Eisen M. Romiplostim treatment for children with immune thrombocytopenia: Results of an integrated database of five clinical trials. Pediatr Blood Cancer. 2020 Nov;67(11):e28630. doi: 10.1002/pbc.28630. Epub 2020 Sep 9.
- Grainger J, Bussel JB, Tarantino MD, Cooper N, Beam D, Despotovic JM, Maschan A, Wang K, Eisen M, Bowers C. A Single-Arm, Long-Term Efficacy and Safety Study of Subcutaneous Romiplostim in Children with Immune Thrombocytopenia. Blood Adv. 2022 Apr 12:bloodadvances.2021006014. doi: 10.1182/bloodadvances.2021006014. Online ahead of print.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Autoimmune Diseases
- Hematologic Diseases
- Hemorrhage
- Hemorrhagic Disorders
- Blood Coagulation Disorders
- Skin Manifestations
- Blood Platelet Disorders
- Thrombotic Microangiopathies
- Purpura, Thrombocytopenic
- Purpura
- Purpura, Thrombocytopenic, Idiopathic
- Thrombocytopenia
Other Study ID Numbers
- 20101221
- 2011-005019-96 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
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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argenxWithdrawnPrimary Immune Thrombocytopenia (ITP)
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Novartis PharmaceuticalsRecruitingPrimary Immune Thrombocytopenia (ITP)China, United States, Spain, Singapore, Austria, Germany, Belgium, Italy, Japan, Czechia, Hong Kong, Hungary, Malaysia, Argentina, Bulgaria, Turkey, Vietnam, Australia, Thailand, Mexico, United Kingdom, France, Romania, Norway, India
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Gruppo Italiano Malattie EMatologiche dell'AdultoCompletedAdult Patients | Immune Primary Thrombocytopenia | Splenectomy | TPO-mimeticsItaly
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Samsung Medical CenterUnknown
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