E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immune Thrombocytopenia (ITP) in Paediatric Subjects |
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E.1.1.1 | Medical condition in easily understood language |
Bleeding disorder - ITP is a condition that may cause easy bruising or bleeding due to an abnormally low number of platelets in the blood. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10043558 |
E.1.2 | Term | Thrombocytopenia purpura |
E.1.2 | System Organ Class | 100000004851 |
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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 |
The primary objective is to evaluate the efficacy of romiplostim in the treatment of thrombocytopenia in pediatric subjects with immune thrombocytopenia (ITP) as measured by durable platelet response. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: • To evaluate overall and weekly platelet response • To evaluate the use of rescue ITP medications • To evaluate a combined bleeding event and rescue medication use endpoint (composite bleeding episodes) • To evaluate the overall safety of romiplostim |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Diagnosis of primary ITP according to the ASH Guidelines at least 6 months prior to screening, regardless of splenectomy status • Subject must be refractory to a prior ITP therapy, having relapsed after at least 1 prior ITP therapy, or ineligible for other ITP therapies -Prior therapy includes first-line therapies •Age ≥ 1 year and < 18 years at the time of providing informed consent • The mean of 2 platelet counts taken during the screening period must be ≤ 30 x 109/L with neither count > 35 x 109/L • A serum creatinine concentration ≤ 1.5 times the laboratory normal range (for each age category) during the screening period • Adequate liver function; -serum bilirubin ≤ 1.5 times the laboratory normal range during the screening period -AST and ALT ≤ 3.0 times the laboratory normal range during the screening period •Hemoglobin > 10.0 g/dL during the screening period • Subject and/or subject’s legally acceptable representative has provided informed consent prior to any study-specific procedure; subject has provided assent, where required |
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E.4 | Principal exclusion criteria |
•Known 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 in the study •Known active or prior malignancy except adequately treated basal cell carcinoma •Known history of congenital thrombocytopenia •Known history of hepatitis B, hepatitis C, or HIV •Known history of H. pylori by urea breath test or stool antigen test within 6 months of enrollment or successfully treated with no evidence of infection •Known history of systemic lupus erythematosus, evans syndrome, or autoimmune neutropenia •Known history of antiphospholipid antibody syndrome or positive for lupus anticoagulant •Known history of disseminated intravascular coagulation, hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura •Previous history of venous thromboembolism or thrombotic events •Previous use of romiplostim, PEG-rHuMGDF, Eltrombopag, rHuTPO or any platelet producing agent •Rituximab (for any indication) or 6-MP within 14 weeks before the screening visit, or anticipated use during the time of the proposed study •Splenectomy within 4 weeks of the screening visit •All hematopoietic growth factors including IL-11 (oprelvekin) within 4 weeks before 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 •Known hypersensitivity to any recombinant E coli-derived product (eg, Infergen, Neupogen, Somatropin, and Actimmune) •Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s) •Subject will have any other investigational procedures performed while enrolled in this clinical study •Subject is pregnant or breast feeding, or planning to become pregnant within 1 month after the end of treatment •Female subject of child bearing potential is not willing to use, in combination with her partner, 2 forms highly effective contraception during treatment and for 1 month after the end of treatment •Subject has known sensitivity to any of the products to be administered during dosing •Subject has previously enrolled into a prior Amgen romiplostim study •Subject will not be available for protocol-required study visits, to the best of the subject’s and investigator’s knowledge •Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the incidence of durable platelet response. A subject with durable platelet response is defined as achieving at least 6 weekly platelet counts of ≥ 50 x 109/L during weeks 18 through 25 of treatment. |
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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) |
• Subject incidence of overall platelet response. Overall responders are defined as subjects who achieve a platelet count ≥ 50 x 109/L at a minimum of 4 times during weeks 2 to 25 of the treatment period • Number of weekly platelet counts ≥ 50 x 109/L during weeks 2 to 25 of the treatment period • Subject incidence of rescue ITP medications used • The number of composite bleeding episodes. The composite bleeding episode is defined as clinically significant bleeding events or the use of a rescue medication to prevent a clinical significant bleeding event during weeks 2 to 25 of the treatment period. A clinically significant event is defined as a CTCAE version 3.0 grade ≥ 2 bleeding event • Incidence of adverse events, including thromboembolic events and hematologic malignancies, clinically significant changes in laboratory values and the incidence of antibody formation |
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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 | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Australia |
Canada |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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The study will end once the last subject participating in the study has completed either the EOS visit (and is eligible for the 20090340 study) or requires continued platelet monitoring and subsequently completes the EOF visit and all data through that respective subject visit is recorded, verified and cleaned. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |