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Trial record 36 of 36 for:    DANAZOL

Long-term Study of Romiplostim in Thrombocytopenic Pediatric Patients With Immune Thrombocytopenia (ITP)

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ClinicalTrials.gov Identifier: NCT02279173
Recruitment Status : Completed
First Posted : October 30, 2014
Results First Posted : August 26, 2019
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

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.

Condition or disease Intervention/treatment Phase
Immune Thrombocytopenia Drug: Romiplostim Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 204 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Open-label, Long-term Efficacy and Safety Study of Romiplostim in Thrombocytopenic Pediatric Subjects With Immune Thrombocytopenia (ITP)
Actual Study Start Date : December 10, 2014
Actual Primary Completion Date : August 30, 2018
Actual Study Completion Date : August 15, 2019


Arm Intervention/treatment
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.
Drug: Romiplostim
Romiplostim subcutaneous weekly injection
Other Name: Nplate




Primary Outcome Measures :
  1. 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. ]

    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.


  2. Percentage of Participants Who Developed Collagen After Exposure to Romiplostim [ Time Frame: Year 1 (Cohort 1) and year 2 (Cohort 2) ]

    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)


  3. Percentage of Participants With Increased Modified Bauermeister Grade [ Time Frame: Baseline, year 1 (Cohort 1) and year 2 (Cohort 2) ]

    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.


  4. Percentage of Participants Who Developed Bone Marrow Abnormalities [ Time Frame: Year 1 (Cohort 1) and year 2 (Cohort 2) ]
    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.


Secondary Outcome Measures :
  1. 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, up to the data cut-off date of 20 March 2017. ]

    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.


  2. Percentage of Time With an Increase in Platelet Count ≥ 20 x10⁹/L Above Baseline [ Time Frame: Baseline and from week 2 to month 36, up to the data cut-off date of 20 March 2017. ]

    The percentage of time with an increase in platelet count ≥ 20 x 10⁹/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/L above baseline was calculated as the number of months the median platelet count was ≥ 20 x10⁹/L above baseline divided by the total number of months assessed.


  3. 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, up to the data cut-off date of 20 March 2017. ]

    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

  4. 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, up to the data cut-off date of 20 March 2017. ]

    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.


  5. Number of Participants With Adverse Events [ Time Frame: From first dose of study drug to the end of treatment (up to 36 months), up to the data cut-off date of 30 August 2018. ]

    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 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.


  6. Percentage of Participants Who Developed Increased Reticulin [ Time Frame: Baseline, year 1 (Cohort 1) and year 2 (Cohort 2) ]

    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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   1 Year to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02279173


  Show 78 Study Locations
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] September 9, 2016
Statistical Analysis Plan  [PDF] September 9, 2016


Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02279173     History of Changes
Other Study ID Numbers: 20101221
2011-005019-96 ( EudraCT Number )
First Posted: October 30, 2014    Key Record Dates
Results First Posted: August 26, 2019
Last Update Posted: September 17, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing
Keywords provided by Amgen:
Pediatric
Immune Thrombocytopenia
Amgen
Additional relevant MeSH terms:
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Thrombocytopenia
Purpura, Thrombocytopenic, Idiopathic
Blood Platelet Disorders
Hematologic Diseases
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms