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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02279173
Ethics application status
Date submitted
1/10/2014
Date registered
30/10/2014
Date last updated
24/08/2020

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 - Platelet response was defined as a platelet count of = 50 x 10?/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.
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 - 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)
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 - 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.
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 - 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.
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 - Platelet response was defined as a platelet count of = 50 x 10?/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.
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 - The percentage of time with an increase in platelet count = 20 x 10? 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 x10? cells/L above baseline was calculated as the number of months the median platelet count was = 20 x10? cells/L above baseline divided by the total number of months assessed.
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 - 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:
corticosteroids
platelet transfusions
Intravenous immunoglobulin (IVIG)
azathioprine
anti-D immunoglobulin
danazol
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 - 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.
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 - 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:
fatal
life threatening
required in-patient hospitalization or prolongation of existing hospitalization
resulted in persistent or significant disability/incapacity
congenital anomaly/birth defect
other medically important serious event Adverse events were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grading scale, where Grade 1 = mild AE; Grade 2 = moderate AE; Grade 3 = severe AE; Grade 4 = life-threatening or disabling; Grade 5 = death related to AE.
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 - 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.
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
Gender
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
N/A
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
State/province [7] 0 0
Nevada
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Belgium
State/province [13] 0 0
Brussels
Country [14] 0 0
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
Country [23] 0 0
Czechia
State/province [23] 0 0
Ostrava-Poruba
Country [24] 0 0
Czechia
State/province [24] 0 0
Praha 5
Country [25] 0 0
France
State/province [25] 0 0
Montpellier cedex 05
Country [26] 0 0
France
State/province [26] 0 0
Nice Cedex 3
Country [27] 0 0
France
State/province [27] 0 0
Paris
Country [28] 0 0
France
State/province [28] 0 0
Vandoeuvre les Nancy
Country [29] 0 0
Hungary
State/province [29] 0 0
Budapest
Country [30] 0 0
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
Country [40] 0 0
Poland
State/province [40] 0 0
Lodz
Country [41] 0 0
Poland
State/province [41] 0 0
Olsztyn
Country [42] 0 0
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
State/province [52] 0 0
Comunidad Valenciana
Country [53] 0 0
Spain
State/province [53] 0 0
Madrid
Country [54] 0 0
Switzerland
State/province [54] 0 0
Basel
Country [55] 0 0
Switzerland
State/province [55] 0 0
St. Gallen
Country [56] 0 0
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/show/NCT02279173
Trial related presentations / publications
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
Other publications