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

A Single Arm, Open-label, Long-term Efficacy and Safety Study of Romiplostim in Thrombocytopenic Pediatric Subjects With Immune Thrombocytopenia (ITP)

Sponsors

Lead Sponsor: Amgen

Source 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.

Overall Status Completed
Start Date December 10, 2014
Completion Date August 15, 2019
Primary Completion Date August 30, 2018
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Percentage of Time With a Platelet Response During the First 6 Months of Treatment Week 2 to Month 6, platelet response was assessed every week.
Percentage of Participants Who Developed Collagen After Exposure to Romiplostim Year 1 (Cohort 1) and year 2 (Cohort 2)
Percentage of Participants With Increased Modified Bauermeister Grade Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)
Percentage of Participants Who Developed Bone Marrow Abnormalities Year 1 (Cohort 1) and year 2 (Cohort 2)
Secondary Outcome
Measure Time Frame
Percentage of Time With a Platelet Response During the Overall Treatment Period From week 2 to the end of the treatment period, 36 months, up to the data cut-off date of 20 March 2017.
Percentage of Time With an Increase in Platelet Count ≥ 20 x10⁹/L Above Baseline Baseline and from week 2 to month 36, up to the data cut-off date of 20 March 2017.
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, up to the data cut-off date of 20 March 2017.
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, up to the data cut-off date of 20 March 2017.
Number of Participants With Adverse Events 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.
Percentage of Participants Who Developed Increased Reticulin Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)
Enrollment 204
Condition
Intervention

Intervention Type: Drug

Intervention Name: Romiplostim

Description: Romiplostim subcutaneous weekly injection

Arm Group Label: Romiplostim

Other Name: Nplate

Eligibility

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

Gender: All

Minimum Age: 1 Year

Maximum Age: 18 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
MD Study Director Amgen
Location
Facility:
Research Site | Roseville, California, 95661, United States
Research Site | Atlanta, Georgia, 30322, United States
Research Site | Chicago, Illinois, 60611, United States
Research Site | Peoria, Illinois, 61615, United States
Research Site | Indianapolis, Indiana, 46260, United States
Research Site | Iowa City, Iowa, 52242, United States
Research Site | Kansas City, Missouri, 64108, United States
Research Site | Las Vegas, Nevada, 89109, United States
Research Site | New York, New York, 10021, United States
Research Site | Cincinnati, Ohio, 45229, United States
Research Site | Columbus, Ohio, 43205, United States
Research Site | Pittsburgh, Pennsylvania, 15224, United States
Research Site | Nashville, Tennessee, 37232, United States
Research Site | Dallas, Texas, 75390, United States
Research Site | Fort Worth, Texas, 76104, United States
Research Site | Houston, Texas, 77030, United States
Research Site | Randwick, New South Wales, 2031, Australia
Research Site | South Brisbane, Queensland, 4101, Australia
Research Site | Parkville, Victoria, 3052, Australia
Research Site | Brussels, 1020, Belgium
Research Site | Bruxelles, 1200, Belgium
Research Site | Gent, 9000, Belgium
Research Site | Leuven, 3000, Belgium
Research Site | Liege, 4000, Belgium
Research Site | Belem, Pará, 66033-000, Brazil
Research Site | Jau, São Paulo, 17210-120, Brazil
Research Site | Sao Paulo, São Paulo, 05403-000, Brazil
Research Site | Sao Paulo, São Paulo, 08270-070, Brazil
Research Site | Hamilton, Ontario, L8S 4K1, Canada
Research Site | Toronto, Ontario, M5G 1X8, Canada
Research Site | Montreal, Quebec, H3T 1C5, Canada
Research Site | Montreal, Quebec, H4A 3J1, Canada
Research Site | Olomouc, 775 20, Czechia
Research Site | Ostrava-Poruba, 708 52, Czechia
Research Site | Praha 5, 150 06, Czechia
Research Site | Montpellier cedex 05, 34295, France
Research Site | Nice Cedex 3, 06202, France
Research Site | Paris, 75019, France
Research Site | Vandoeuvre les Nancy, 54511, France
Research Site | Budapest, 1094, Hungary
Research Site | Debrecen, 4032, Hungary
Research Site | Szeged, 6720, Hungary
Research Site | Beer Sheva, 84101, Israel
Research Site | Haifa, 31096, Israel
Research Site | Jerusalem, 91120, Israel
Research Site | Petach Tikvah, 49202, Israel
Research Site | Tel Aviv, 64239, Israel
Research Site | Tel Hashomer, 52621, Israel
Research Site | Monterrey, Nuevo León, 64460, Mexico
Research Site | Bydgoszcz, 85-094, Poland
Research Site | Lodz, 91-738, Poland
Research Site | Olsztyn, 10-561, Poland
Research Site | Zabrze, 41-800, Poland
Research Site | Krasnodar, 350007, Russian Federation
Research Site | Moscow, 117198, Russian Federation
Research Site | Moscow, 117997, Russian Federation
Research Site | Saint-Petersburg, 197022, Russian Federation
Research Site | Saratov, 410028, Russian Federation
Research Site | Volgograd, 400138, Russian Federation
Research Site | Johannesburg, Gauteng, 2013, South Africa
Research Site | Parktown, Gauteng, 2193, South Africa
Research Site | Durban, KwaZulu-Natal, 4001, South Africa
Research Site | Tygerberg, Western Cape, 7505, South Africa
Research Site | Barcelona, Cataluña, 08035, Spain
Research Site | Esplugues de Llobregat, Cataluña, 08950, Spain
Research Site | Valencia, Comunidad Valenciana, 46026, Spain
Research Site | Madrid, 28009, Spain
Research Site | Madrid, 28046, Spain
Research Site | Basel, 4056, Switzerland
Research Site | St. Gallen, 9006, Switzerland
Research Site | Zuerich, 8032, Switzerland
Research Site | Adana, 01130, Turkey
Research Site | Antalya, 07059, Turkey
Research Site | Izmir, 35100, Turkey
Research Site | Birmingham, B4 6NH, United Kingdom
Research Site | Edinburgh, EH9 1LF, United Kingdom
Research Site | London, W12 0HS, United Kingdom
Research Site | Manchester, M13 9WL, United Kingdom
Location Countries

Australia

Belgium

Brazil

Canada

Czechia

France

Hungary

Israel

Mexico

Poland

Russian Federation

South Africa

Spain

Switzerland

Turkey

United Kingdom

United States

Verification Date

September 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Romiplostim

Type: Experimental

Description: 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.

Patient Data Yes
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov