Clinical trial NCT02279173: Long-term Study of Romiplostim in Thrombocytopenic Pediatric Patients With Immune Thrombocytopenia (ITP)
Official title: A Single Arm, Open-label, Long-term Efficacy and Safety Study of Romiplostim in Thrombocytopenic Pediatric Subjects With Immune Thrombocytopenia (ITP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Immune Thrombocytopenia
Keywords: Pediatric
Immune Thrombocytopenia
Amgen
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2014-10-30
Enrollment: 203
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Time With a Platelet Response During the First 6 Months of Treatment
timeFrame: Week 2 to Month 6, platelet response was assessed every week.
measure: Percentage of Participants Who Developed Collagen After Exposure to Romiplostim
timeFrame: Year 1 (Cohort 1) and year 2 (Cohort 2)
measure: Percentage of Participants With Increased Modified Bauermeister Grade
timeFrame: Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)
measure: Percentage of Participants Who Developed Bone Marrow Abnormalities
timeFrame: Year 1 (Cohort 1) and year 2 (Cohort 2)
Secondary outcomes:
measure: Percentage of Time With a Platelet Response During the Overall Treatment Period
timeFrame: From week 2 to the end of the treatment period, 36 months
measure: Percentage of Time With an Increase in Platelet Count ≥ 20 x 10⁹ Cells/L Above Baseline
timeFrame: Baseline and from week 2 to month 36
measure: Number of Participants Reporting Use of Rescue Medications for ITP During the Treatment Period
timeFrame: From first dose of romiplostim to the end of the treatment period, 36 months
measure: Number of Participants Who Developed Anti-Romiplostim or Anti-Thrombopoietin Neutralizing Antibodies
timeFrame: Week 12, week 52 and every 24 weeks thereafter up to month 36
measure: Number of Participants With Adverse Events
timeFrame: 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).
measure: Percentage of Participants Who Developed Increased Reticulin
timeFrame: Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)
Other outcomes:
Locations:
city: Roseville
country: United States
facility: Research Site
state: California
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Peoria
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Iowa City
country: United States
facility: Research Site
state: Iowa
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: New York
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
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state: Ohio
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Fort Worth
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Randwick
country: Australia
facility: Research Site
state: New South Wales
city: South Brisbane
country: Australia
facility: Research Site
state: Queensland
city: Parkville
country: Australia
facility: Research Site
state: Victoria
city: Brussels
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Belem
country: Brazil
facility: Research Site
state: Pará
city: Jau
country: Brazil
facility: Research Site
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Research Site
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Research Site
state: São Paulo
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Olomouc
country: Czechia
facility: Research Site
city: Ostrava-Poruba
country: Czechia
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Montpellier cedex 05
country: France
facility: Research Site
city: Nice Cedex 3
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Vandoeuvre les Nancy
country: France
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Beer Sheva
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Petach Tikvah
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Tel Hashomer
country: Israel
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
state: Nuevo León
city: Bydgoszcz
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Zabrze
country: Poland
facility: Research Site
city: Krasnodar
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saratov
country: Russian Federation
facility: Research Site
city: Volgograd
country: Russian Federation
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
state: Gauteng
city: Parktown
country: South Africa
facility: Research Site
state: Gauteng
city: Durban
country: South Africa
facility: Research Site
state: KwaZulu-Natal
city: Tygerberg
country: South Africa
facility: Research Site
state: Western Cape
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Esplugues de Llobregat
country: Spain
facility: Research Site
state: Cataluña
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Basel
country: Switzerland
facility: Research Site
city: St. Gallen
country: Switzerland
facility: Research Site
city: Zuerich
country: Switzerland
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Antalya
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.