E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chemotherapy-induced anemia (CIA) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064469 |
E.1.2 | Term | Anemia post chemotherapy |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of darbepoetin alfa with respect to the change in hemoglobin level, compared with placebo, when administered once every three weeks (Q3W) at doses of 4.5 μg/kg and 6.75 μg/kg to paediatric subjects with a diagnosis of Ewing’s sarcoma, neuroblastoma, osteosarcoma, soft tissue sarcoma or medulloblastoma |
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E.2.2 | Secondary objectives of the trial |
To evaluate the incidence of Red Blood Cell (RBC) transfusion To summarize the volume of RBC transfused To evaluate categorical changes in hemoglobin level compared to baseline To characterize darbepoetin alfa pharmacokinetics (PK) To assess safety and tolerability |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
This study will include a ‘pharmacokinetic’ or ‘PK’ sub-study. This will examine what happens to darbepoetin alfa once it enters the body. Approximately 36 patients out of 225 patients will participate in the PK study at a select number of centers. |
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E.3 | Principal inclusion criteria |
Disease Related • Diagnosed with Ewing’s sarcoma, neuroblastoma, osteosarcoma, soft tissue sarcoma or medulloblastoma • Currently receiving non-myeloablative chemotherapy treatment and expecting to receive at least a further 9 weeks of chemotherapy
Demographic • Male or female age 1 to 18 years of age at randomisation • ECOG performance status of 0, 1, or 2 assessed by the investigator at screening
Laboratory • Screening hemoglobin level ≤ 10.0 g/dL. (If screening takes more than 7 days, confirmation hemoglobin must be performed within 7 days before randomisation.)
Ethical • A legal guardian willing and able to provide written informed consent and subject is willing and able to provide written assent, when required. Written informed consent and subject assent, when required, must be obtained from the legally accepted representative before any study-specific procedures are performed |
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E.4 | Principal exclusion criteria |
Disease Related • Anemia related to nutritional deficiencies per investigator judgement • Planned myeloablative radiation therapy during the screening or treatment periods • Planned myeloablative therapy (eg bone marrow transplant) within 3 weeks following the last dose of investigational product • Diagnosis of conditions not related to chemotherapy which cause anemia (eg, gastrointestinal bleeding, renal disease) • Unstable cardiac condition per investigator judgement • Uncontrolled hypertension per investigator judgement • Documented history of pure red cell aplasia • History of clinically significant venous thromboembolic event (VTE) within 6 months of screening (clinically significant VTE does not include superficial thrombosis) Laboratory • Received any RBC transfusion within 21 days before randomisation • Plan to receive any RBC transfusion between randomisation and study day 1 • Inadequate renal and/or liver function: creatinine > 2X ULN and/or transaminases > 5X ULN (>10 X ULN if the subject is receiving methotrexate treatment) • Known positive test of human immunodeficiency virus (HIV) • Transferrin saturation < 15% and ferritin < 22.5 pmol/L (< 10 ng/mL) at screening. Medications • Previous use of investigational agent(s) or devices not approved for any indication during the 30 days prior to the first screening visit • Known previous treatment failure to erythropoiesis stimulating agent (ESA) (ie, rHuEpo, darbepoetin alfa) • ESA therapy at any time during the 28 days prior to screening General • Subjects of reproductive potential who are pregnant, breast feeding or not using effective contraceptive precautions in the judgement of the investigator (including females of childbearing potential who are partners of male subjects) • Previously randomised to this trial • Known hypersensitivity to recombinant ESAs or the excipients contained within the investigational product • Confirmed history of neutralizing antibody activity to rHuEpo or darbepoetin alfa • Any condition that compromises the ability of the subject or legal representative to give written informed consent and/or comply with study instructions and procedures |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in hemoglobin value from baseline to End of Treatment Period (EOTP). The baseline hemoglobin value is the value measured on study day 1 prior to first administration of IP. The EOTP hemoglobin value is defined as the last hemoglobin value during the treatment period that is not within a 28 day window following a RBC transfusion. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 | Information not present in EudraCT |
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 |
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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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End of study will occur after all subjects have completed the 25-week treatment period and completed an EOS visit 2 weeks thereafter. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |