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

NCT02279173 | Completed Phase 3 Results

• 2 other identifiers: 201012212011-005019-96
• Study Type: interventional
• Target: 203
• Locations: 17 countries
• Sites: 78

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.

Conditions

Immune Thrombocytopenia

Keywords

Pediatric; Immune Thrombocytopenia; Amgen

Outcome Measures

Primary Outcomes (4)

• 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 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.

• 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)

  Year 1 (Cohort 1) and year 2 (Cohort 2)

• 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.

  Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)

• 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.

  Year 1 (Cohort 1) and year 2 (Cohort 2)

Secondary Outcomes (6)

• Percentage of Time With a Platelet Response During the Overall Treatment Period

  From week 2 to the end of the treatment period, 36 months

• Percentage of Time With an Increase in Platelet Count ≥ 20 x 10⁹ Cells/L Above Baseline

  Baseline and from week 2 to month 36

• Number of Participants Reporting Use of Rescue Medications for ITP During the Treatment Period

  From first dose of romiplostim to the end of the treatment period, 36 months

• Number of Participants Who Developed Anti-Romiplostim or Anti-Thrombopoietin Neutralizing Antibodies

  Week 12, week 52 and every 24 weeks thereafter up to month 36

• Number of Participants With Adverse Events

  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).

Study Arms (1)

Romiplostim

EXPERIMENTAL

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

Interventions

Romiplostim DRUG

Romiplostim subcutaneous weekly injection

Also known as: Nplate

Romiplostim

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (78)

Research Site

Roseville, California, 95661, United States

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Atlanta, Georgia, 30322, United States

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Chicago, Illinois, 60611, United States

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Peoria, Illinois, 61615, United States

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Indianapolis, Indiana, 46260, United States

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Iowa City, Iowa, 52242, United States

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Kansas City, Missouri, 64108, United States

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Las Vegas, Nevada, 89109, United States

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New York, New York, 10021, United States

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Cincinnati, Ohio, 45229, United States

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Columbus, Ohio, 43205, United States

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Pittsburgh, Pennsylvania, 15224, United States

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Nashville, Tennessee, 37232, United States

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Dallas, Texas, 75390, United States

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Fort Worth, Texas, 76104, United States

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Houston, Texas, 77030, United States

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Randwick, New South Wales, 2031, Australia

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South Brisbane, Queensland, 4101, Australia

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Parkville, Victoria, 3052, Australia

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Brussels, 1020, Belgium

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Belém, Pará, 66033-000, Brazil

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Jaú, São Paulo, 17210-120, Brazil

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São Paulo, São Paulo, 05403-000, Brazil

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São Paulo, São Paulo, 08270-070, Brazil

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Hamilton, Ontario, L8S 4K1, Canada

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Toronto, Ontario, M5G 1X8, Canada

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Montreal, Quebec, H3T 1C5, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Olomouc, 775 20, Czechia

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Ostrava-Poruba, 708 52, Czechia

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Prague, 150 06, Czechia

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Montpellier, 34295, France

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Nice, 06202, France

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Paris, 75019, France

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Vandœuvre-lès-Nancy, 54511, France

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Budapest, 1094, Hungary

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Debrecen, 4032, Hungary

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Szeged, 6720, Hungary

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Beersheba, 84101, Israel

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Haifa, 31096, Israel

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Jerusalem, 91120, Israel

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Petach Tikvah, 49202, Israel

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Tel Aviv, 64239, Israel

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Tel Litwinsky, 52621, Israel

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Monterrey, Nuevo León, 64460, Mexico

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Bydgoszcz, 85-094, Poland

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Lodz, 91-738, Poland

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Olsztyn, 10-561, Poland

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Zabrze, 41-800, Poland

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Krasnodar, 350007, Russia

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Moscow, 117198, Russia

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Moscow, 117997, Russia

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Saint Petersburg, 197022, Russia

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Saratov, 410028, Russia

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Volgograd, 400138, Russia

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Johannesburg, Gauteng, 2013, South Africa

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Parktown, Gauteng, 2193, South Africa

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Durban, KwaZulu-Natal, 4001, South Africa

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Tygerberg, Western Cape, 7505, South Africa

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Barcelona, Catalonia, 08035, Spain

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Esplugues de Llobregat, Catalonia, 08950, Spain

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Valencia, Valencia, 46026, Spain

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Madrid, 28009, Spain

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Madrid, 28046, Spain

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Basel, 4056, Switzerland

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Sankt Gallen, 9006, Switzerland

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Zurich, 8032, Switzerland

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Adana, 01130, Turkey (Türkiye)

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Antalya, 07059, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Birmingham, B4 6NH, United Kingdom

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Edinburgh, EH9 1LF, United Kingdom

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London, W12 0HS, United Kingdom

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Manchester, M13 9WL, United Kingdom

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Related Publications (2)

• 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.

  PMID: 32902132 BACKGROUND

• 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.

  PMID: 35413092 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

romiplostim

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2014
• First Posted: October 30, 2014
• Study Start: December 10, 2014
• Primary Completion: August 30, 2018
• Study Completion: August 8, 2019
• Last Updated: June 23, 2022
• Results First Posted: August 28, 2019

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

PL (4); ME (1); GB (4); CZ (3); AU (3); TU (3); IL (6); CH (3); FR (4); BE (5); BR (4); RU (6); US (16); HU (3); ES (5); CA (4); ZA (4)