E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Thrombocytopenia associated with ITP |
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E.1.1.1 | Medical condition in easily understood language |
Thrombocytopenia
Idiopathic Thrombocytopenic Purpura
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the incidence of collagen fibrosis as evidenced by trichrome staining at Year 1, Year 2, or Year 3 after initial exposure of romiplostim. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the presence of collagen fibrosis as evidenced by trichrome staining 12 weeks after romiplostim discontinuation in subjects who developed collagen fibrosis at Year 1, Year 2, or Year 3 after exposure of romiplostim.
• To evaluate the incidence of increased reticulin fibrosis as evidenced by silver staining at Year 1, Year 2, or Year 3 after exposure of romiplostim.
• To evaluate electrocardiogram (ECG) changes after exposure to romiplostim.
• To evaluate the incidence of cytopenias (anemia or neutropenia) after exposure to romiplostim.
• To evaluate the overall safety as evidenced by adverse events and the development of neutralizing antibodies to romiplostim or cross-reacting antibodies to endogenous thrombopoietin. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Diagnosis of ITP according to the American Society of Hematology (ASH) guidelines
• Subject must have had a bone marrow biopsy within one year prior to planned first dose of romiplostim (with available bone marrow tissue block or unstained histological slides to send to a central laboratory for interpretation) or must consent to a pre-treatment bone marrow biopsy within 3 weeks prior to planned first dose of romiplostim. Central laboratory interpretation is required prior to first dose of romiplostim
• Baseline bone marrow reticulin grade of 0, 1, 2 or 3 according to the modified Bauermeister grading scheme as assessed by central laboratory interpretation
• Subject must agree to a scheduled bone marrow biopsy at Year 1, Year 2, or Year 3 following romiplostim treatment and any unscheduled biopsies if clinically indicated
• Subject platelet count is < 50x 10*9/L
• Subject ≥18 years of age
• Must have received at least 1 prior ITP therapy (examples of ITP therapy include corticosteroids, IVIG, splenectomy)
• Subject (or legally-acceptable representative) is willing and able to provide written informed consent |
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E.4 | Principal exclusion criteria |
• Baseline bone marrow biopsy positive for collagen fibrosis
• Any known history of or currently active bone marrow stem cell disorder, hematological malignancy, myeloproliferative disorder, or myelodysplastic syndrome
• Any current active malignancy
• Any prior exposure to cytostatic chemotherapy or radiotherapy for malignancy
• Subject has undergone pacemaker placement, cardiac ablation of arrhythmia, and/or any current treatment with Vaughan Williams Class IA – IC and Class III agents
• Subject has participated in any study evaluating PEG-rHuMGDF, recombinant human thrombopoietin (rHuTPO), or thrombopoietin receptor agonists (ie romiplostim or eltrombopag)
• Subject has a known hypersensitivity to any recombinant E coli-derived product
• Subject is currently enrolled in or has not yet completed (at least 4 weeks since ending) other investigational device or drug trial(s) or subject is receiving other investigational agent(s)
• Other investigational procedures are excluded
• Subject of child-bearing potential is evidently pregnant (eg, positive pregnancy test) or is breast feeding
• Subject is not using adequate contraceptive precautions
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and does not have a legally acceptable representative and/or is unable to comply with study procedures |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the incidence of collagen fibrosis as evidenced by trichrome staining at Years 1, 2, or 3 after initial romiplostim exposure using the modified Bauermeister grading scale. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• The incidence of collagen fibrosis as evidenced by trichrome staining 12 weeks after romiplostim discontinuation in subjects who developed collagen fibrosis at Years 1, 2, or 3 after initial exposure of romiplostim using the modified Bauermeister grading scale.
• The incidence of bone marrow reticulin increases by ≥ 2 severity grades or increase to grade 4 (ie, grade 0 to 2-4, 1 to 3-4, 2 to 4, or 3 to 4) over baseline as evidenced by reticulin silver staining at Year 1, Year 2, or Year 3 post romiplostim exposure using the modified Bauermeister grading scale.
• The incidence of clinically relevant changes in QT/QTc intervals, as defined as an absolute QTc interval > 500 ms or a QTc interval increase from baseline ≥ 60 ms post romiplostim exposure.
• The incidence of any improvement of reticulin to a grade of ≤ 2 for subjects who developed grade 3 reticulin after initial exposure to romiplostim as measured by the modified Bauermeister grading scale.
• The incidence of CTCAE grade ≥ 2 shift in anemia or neutropenia post romiplostim exposure.
• The incidence and severity of all adverse events including clinically significant changes in laboratory values.
• The incidence of neutralizing antibody formation to romiplostim or cross-reacting antibodies to endogenous thrombopoietin. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Mexico |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of study will be defined as the date the last subject completes
their End of Study (EOS) visit |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |