Efficacy and Safety Study of Romiplostim in Paediatrics with Immune Thrombocytopenia

• Register: EUCTR
• Last refreshed on: 6 January 2015
• Main ID: EUCTR2011-005019-96-Outside-EU/EEA
• Date of registration: 24/09/2014
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: Efficacy and Safety Study of Romiplostim in Paediatrics with Immune Thrombocytopenia
• Scientific title: A Single Arm, Open-label, Long-term Efficacy and Safety Study of Romiplostim in Thrombocytopenic Pediatric Subjects With Immune Thrombocytopenia (ITP)
• Target sample size: 200
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005019-96
• 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 Number of treatment arms in the trial: 1

Countries of recruitment

Australia, Brazil, Canada, Israel, Mexico, Peru, Russian Federation, South Africa, Switzerland, Turkey, United States

Contacts

• Name: IHQ Medical Information - Clinical
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ Medical Information - Clinical
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
• Diagnosis of primary ITP according to The American Society of Hematology (ASH) Guidelines (Neunert et al, 2011) at least 6 months before screening, regardless of splenectomy status
• Age = 1 year and < 18 years at the time of providing informed consent
• Subject must be refractory to a prior ITP therapy, having relapsed after at least 1 prior ITP therapy, or be ineligible for other ITP therapies
• Examples of prior therapy include but are not limited to:
corticosteroids, IVIG, anti-D immunoglobulin, and platelet transfusions.
Subjects who have failed a splenectomy are eligible for study participation
• Subject has a documented platelet count = 30 x10 (to the)9/L or is experiencing bleeding that is uncontrolled with conventional therapies
• Subject's legally acceptable representative (or subject, if applicable) has provided informed consent before any study-specific procedure; and subject has proved assent, where required by the IRB/IEC
• Adequate hematologic, renal, and liver function during the screening period:
-Hemoglobin > 10.0 g/dL
-Serum creatinine = 1.5 times the upper limit of normal
-Total serum bilirubin = 1.5 times the upper limit of normal
-AST and ALT = 3.0 times the upper limit of normal
Are the trial subjects under 18? yes
Number of subjects for this age range: 200
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Exclusion Criteria
• Known 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 in the study)
• Prior bone marrow transplant or peripheral blood progenitor cell transplant
• Known active or prior malignancy except non-melanoma skin cancers within the last 5 years
• Known history of myelodysplastic syndrome
• Known history of bleeding diathesis
• Known history of congenital thrombocytopenia
• Known history of hepatitis B, hepatitis C or human immunodeficiency virus
• Known history of systemic lupus erythematosus, Evans syndrome, or autoimmune neutropenia
• Known history of antiphospholipid antibody syndrome or known positive for lupus anticoagulant
• Known history of disseminated intravascular coagulation, hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura
• History of venous thromboembolism or thrombotic events
• Previous use of romiplostim. Previous use of eltrombopag within 4 weeks of enrollment.
• Previous use of 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 another investigational device or drug
study(s), or receiving other investigational agent(s)
• Subject will have investigational procedures performed while enrolled in this clinical study
• Female subject of child bearing potential (defined as having first menses) is 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®)
• Subject has previously enrolled into this study
• Subject will not be available for protocol-required study visits or procedures, to the best of the subject's and investigator's knowledge
• Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written
informed consent and/or to comply with all required study procedures


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Immune Thrombocytopenia (ITP) in Paediatric Subjects
MedDRA version: 17.1 Level: LLT Classification code 10043558 Term: Thrombocytopenia purpura System Organ Class: 100000004851

Intervention(s)

Trade Name: Nplate
Product Name: Nplate
Product Code: AMG 531
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: romiplostim
CAS Number: 267639-76-9
Current Sponsor code: AMG 531
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.5-

Primary Outcome(s)

Secondary Objective: The secondary objectives of the study are:
• To describe the percentage of time that pediatric subjects with ITP have a platelet response over the study duration
• To describe the percentage of time that pediatric subjects with ITP have an increase in platelet count = 20 x 10 (to the ) 9/L above baseline over the study duration
• To describe the use of rescue ITP medications
• To describe the incidence of antibody formation
• To describe the safety of romiplostim as a long-term treatment in pediatric thrombocytopenic subjects with ITP

Main Objective: The primary objective is to describe the percentage of time that pediatric subjects with immune thrombocytopenia (ITP) have a platelet response in the first 6 months from the start of treatment with romiplostim.

Primary end point(s): The percentage of time with a platelet count of = 50 x 10 (to the) 9/L starting from week 2 in the first 6 months of the treatment period
without rescue medication use within the past 4 weeks
In addition, for protocol supplement:
• Evaluation of bone marrow changes after Year 1 and Year 2 for the following:
- Incidence of collagen as evidenced by trichrome staining (using the modified Bauermeister grading scale) after romiplostim exposure
- Incidence of bone marrow reticulin increases in severity = 2 grades (ie, grade 0 to 2-4, 1 to 3-4, 2 to 4), compared to baseline, or an increase to grade 3 or grade 4 as evidenced by reticulin silver staining using the modified Bauermeister
grading scale after romiplostim exposure
- Incidence of bone marrow abnormalities (eg, myelodysplastic syndrome, monosomy 7) as evidenced by cytogenetics and fluorescence
in situ hybridization

Timepoint(s) of evaluation of this end point: From week 2

Secondary Outcome(s)

Secondary end point(s): The percentage of time with a platelet count of = 50 x 10 (to the) 9/L starting from week 2 until the end of the treatment period without rescue medication use within the past 4 weeks
• The percentage of time with an increase in platelet count = 20 x 10 (to the) 9/L above baseline starting from week 2 until the end of the treatment period without rescue medication use in the past 4 weeks.
• Subject incidence of rescue ITP medications used
• The incidence of anti-romiplostim neutralizing antibodies and cross reactive antibodies to TPO at any time during the study
• The incidence of adverse events, including clinically significant changes in laboratory values
In addition, for protocol supplement:
• The incidence of increased reticulin as evidenced by silver staining at Year 1 or Year 2, after exposure to romiplostim

Timepoint(s) of evaluation of this end point: From week 2

Secondary ID(s)

20101221

2011-005019-96-CZ

Source(s) of Monetary Support

Amgen Inc.