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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02279173




Registration number
NCT02279173
Ethics application status
Date submitted
1/10/2014
Date registered
30/10/2014
Date last updated
23/06/2022

Titles & IDs
Public title
Long-term Study of Romiplostim in Thrombocytopenic Pediatric Patients With Immune Thrombocytopenia (ITP)
Scientific title
A Single Arm, Open-label, Long-term Efficacy and Safety Study of Romiplostim in Thrombocytopenic Pediatric Subjects With Immune Thrombocytopenia (ITP)
Secondary ID [1] 0 0
2011-005019-96
Secondary ID [2] 0 0
20101221
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Immune Thrombocytopenia 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Romiplostim

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 10?/L.


Treatment: Drugs: Romiplostim
Romiplostim subcutaneous weekly injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Time With a Platelet Response During the First 6 Months of Treatment
Timepoint [1] 0 0
Week 2 to Month 6, platelet response was assessed every week.
Primary outcome [2] 0 0
Percentage of Participants Who Developed Collagen After Exposure to Romiplostim
Timepoint [2] 0 0
Year 1 (Cohort 1) and year 2 (Cohort 2)
Primary outcome [3] 0 0
Percentage of Participants With Increased Modified Bauermeister Grade
Timepoint [3] 0 0
Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)
Primary outcome [4] 0 0
Percentage of Participants Who Developed Bone Marrow Abnormalities
Timepoint [4] 0 0
Year 1 (Cohort 1) and year 2 (Cohort 2)
Secondary outcome [1] 0 0
Percentage of Time With a Platelet Response During the Overall Treatment Period
Timepoint [1] 0 0
From week 2 to the end of the treatment period, 36 months
Secondary outcome [2] 0 0
Percentage of Time With an Increase in Platelet Count = 20 x 10? Cells/L Above Baseline
Timepoint [2] 0 0
Baseline and from week 2 to month 36
Secondary outcome [3] 0 0
Number of Participants Reporting Use of Rescue Medications for ITP During the Treatment Period
Timepoint [3] 0 0
From first dose of romiplostim to the end of the treatment period, 36 months
Secondary outcome [4] 0 0
Number of Participants Who Developed Anti-Romiplostim or Anti-Thrombopoietin Neutralizing Antibodies
Timepoint [4] 0 0
Week 12, week 52 and every 24 weeks thereafter up to month 36
Secondary outcome [5] 0 0
Number of Participants With Adverse Events
Timepoint [5] 0 0
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).
Secondary outcome [6] 0 0
Percentage of Participants Who Developed Increased Reticulin
Timepoint [6] 0 0
Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)

Eligibility
Key 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
Minimum age
1 Year
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/12/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/08/2019
Sample size
Target
Accrual to date
Final
203
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Research Site - Randwick
Recruitment hospital [2] 0 0
Research Site - South Brisbane
Recruitment hospital [3] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
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Nevada
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United States of America
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New York
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United States of America
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Ohio
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United States of America
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Pennsylvania
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United States of America
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Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
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Belgium
State/province [13] 0 0
Brussels
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Belgium
State/province [14] 0 0
Bruxelles
Country [15] 0 0
Belgium
State/province [15] 0 0
Gent
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Belgium
State/province [17] 0 0
Liege
Country [18] 0 0
Brazil
State/province [18] 0 0
Pará
Country [19] 0 0
Brazil
State/province [19] 0 0
São Paulo
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
Czechia
State/province [22] 0 0
Olomouc
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Czechia
State/province [23] 0 0
Ostrava-Poruba
Country [24] 0 0
Czechia
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Praha 5
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France
State/province [25] 0 0
Montpellier cedex 05
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France
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Nice Cedex 3
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France
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Paris
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France
State/province [28] 0 0
Vandoeuvre les Nancy
Country [29] 0 0
Hungary
State/province [29] 0 0
Budapest
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Hungary
State/province [30] 0 0
Debrecen
Country [31] 0 0
Hungary
State/province [31] 0 0
Szeged
Country [32] 0 0
Israel
State/province [32] 0 0
Beer Sheva
Country [33] 0 0
Israel
State/province [33] 0 0
Haifa
Country [34] 0 0
Israel
State/province [34] 0 0
Jerusalem
Country [35] 0 0
Israel
State/province [35] 0 0
Petach Tikvah
Country [36] 0 0
Israel
State/province [36] 0 0
Tel Aviv
Country [37] 0 0
Israel
State/province [37] 0 0
Tel Hashomer
Country [38] 0 0
Mexico
State/province [38] 0 0
Nuevo León
Country [39] 0 0
Poland
State/province [39] 0 0
Bydgoszcz
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Poland
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Lodz
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Poland
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Olsztyn
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Poland
State/province [42] 0 0
Zabrze
Country [43] 0 0
Russian Federation
State/province [43] 0 0
Krasnodar
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Moscow
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Saint-Petersburg
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Saratov
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Volgograd
Country [48] 0 0
South Africa
State/province [48] 0 0
Gauteng
Country [49] 0 0
South Africa
State/province [49] 0 0
KwaZulu-Natal
Country [50] 0 0
South Africa
State/province [50] 0 0
Western Cape
Country [51] 0 0
Spain
State/province [51] 0 0
Cataluña
Country [52] 0 0
Spain
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Comunidad Valenciana
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Spain
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Madrid
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Switzerland
State/province [54] 0 0
Basel
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Switzerland
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St. Gallen
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Switzerland
State/province [56] 0 0
Zuerich
Country [57] 0 0
Turkey
State/province [57] 0 0
Adana
Country [58] 0 0
Turkey
State/province [58] 0 0
Antalya
Country [59] 0 0
Turkey
State/province [59] 0 0
Izmir
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Birmingham
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Edinburgh
Country [62] 0 0
United Kingdom
State/province [62] 0 0
London
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase 3b single arm, open label, multicenter study describing the percentage of time pediatric participants with ITP have a platelet response while receiving romiplostim, defined as a platelet count = 50 x 10\^9/L in the absence of ITP rescue medications for the past 4 weeks.
Trial website
https://clinicaltrials.gov/study/NCT02279173
Trial related presentations / 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 J, Tarantino M, Cooper N, Beam D, Despotovic J, 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. 2023 Feb 14;7(3):396-405. doi: 10.1182/bloodadvances.2021006014.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02279173