E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with non-myeloid malignancies associated with Chemotherapy Induced Anemia (CIA). |
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E.1.1.1 | Medical condition in easily understood language |
Patients with malignancies that have their origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord, and who has anemia caused by chemotherapy. |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064014 |
E.1.2 | Term | Cancer anemia |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022972 |
E.1.2 | Term | Iron deficiency anaemia |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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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 |
The primary objective of the study is: - To demonstrate that intravenous iron isomaltoside 1000 is non-inferior to oral iron sulfate in the ability to increase/maintain hemoglobin (Hb) concentration in patients with chemotherapy induced anemia (CIA) and either absolute or functional iron deficiency. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: - To obtain safety reassurance with the use of iron isomaltoside 1000 (Monofer®) in subjects with non-myeloid malignancies and CIA. - To compare study drug related adverse events after iron isomaltoside 1000 (Monofer®) to study drug related adverse events in subjects treated with oral iron sulfate. - To compare iron related hematological parameters (hemoglobin (Hb), transferrin saturation (TfS), serum iron, total iron binding capacity (TIBC), and serum ferritin levels). - To assess subjects who discontinue study due to lack of response or intolerance. - To assess Quality of Life. - Assessment of RLS symptoms and change in these symptoms during the study. - To detect the impact of the study drug upon the ability to complete the planned chemotherapy - To detect the impact of the study drug upon response to the chemotherapy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria: 1. Men and women, aged more than 18 years. 2. Subjects diagnosed with non-myeloid malignancies ( including all solid tumors, Low Grade Lymphoma (LGL), High Grade Lymphoma (HGL), Chronic Lymphatic Leukemia (CLL) and Myeloma) receiving chemotherapy at least 1 day prior to screening and who are going to receive at least two more chemotherapy cycles. 3. Hb < 12 g/dL (7.4 mmol/L). 4. TfS <50%. 5. Serum Ferritin <800 ng/ml. 6. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 7. Willingness to participate after informed consent (including HIPAA, if applicable). |
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E.4 | Principal exclusion criteria |
Exclusion criteria: 1. Anemia caused primarily by other factors than CIA. 2. IV or oral iron treatment within 4 weeks prior to screening visit. 3. Erythrypoietin treatment within 4 weeks prior to screening visit. 4. Blood transfusion within 4 weeks prior to screening visit. 5. Imminent expectation of blood transfusion on part of treating physician. 6. Iron overload or disturbances in utilization of iron (e.g. haemochromatosis and haemosiderosis). 7. Drug hypersensitivity (i.e. previous hypersensitivity to Iron Dextran or iron mono- or disaccharide complexes or to iron sulfate). 8. Known hypersensitivity to any excipients in the investigational drug products. 9. Subjects with a history of multiple allergies. 10. Decompensated liver cirrhosis or active hepatitis (alanine aminotransferase (ALAT) > 3 times upper normal limit). 11. Active acute or chronic infections (assessed by clinical judgement and if deemed necessary by investigator supplied with white blood cells (WBC) and C-reactive protein (CRP)). 12. Rheumatoid arthritis with symptoms or signs of active joint inflammation. 13. Pregnancy and nursing (To avoid pregnancy, women have to be postmenopausal (at least 12 months must have elapsed since last menstruation), surgically sterile, or women of child bearing potential must use one of the following contraceptives during the whole study period and after the study has ended for at least 5 times plasma biological half-life of the investigational medicinal product: Contraceptive pills, intrauterine devices (IUD), contraceptive depot injections (prolonged-release gestagen), subdermal implantation, vaginal ring, and transdermal patches). 14. Planned elective surgery during the study. 15. Participation in any other clinical study (except chemotherapy protocol) within 3 months prior to screening. 16. Known intolerance to oral iron treatment. 17. Untreated B12 or folate deficiency. 18. Any other medical condition that, in the opinion of Principal Investigator, may cause the subject to be unsuitable for the completion of the study or place the subject at potential risk from being in the study. Example, Uncontrolled Hypertension, Unstable Ischemic Heart Disease or Uncontrolled Diabetes Mellitus. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is: Change in Hb concentration from baseline to week 4. |
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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 secondary end points are: - Proportion of subjects who achieve target limits of Hb (men 13–18 g/dL, women 12-16 g/dL) and have change in Hb concentration ≥ 1.0 g/dL at week 2, 4, 8, or 12. - Proportion of subjects who have a change in Hb concentration ≥ 2.0 g/dL at week 2, or 4. - Proportion of subjects who have a change in Hb concentration ≥ 2.0 g/dL at week 2, 4, 8, or 12. - Safety laboratory assessments at baseline and 1, 2, 4, 8, 12 and 24 weeks. - Number of study drug related adverse events (including serious adverse reactions) in iron isomaltoside 1000 (Monofer®) group and iron sulfate group. - Number of adverse events of special interest (i.e. hypersensitivity reactions or hypotension at pre-specified time points in relation to administration of study drug). - Number of subjects receiving transfusions. - Change from baseline in Hb at week 1, 2, 8, 12, and 24. - Change from baseline in serum ferritin, serum iron, TIBC, and TfS measured at week 1, 2, 4, 8, 12 and 24. - Number of subjects in each randomization group who discontinue study because of lack of response or intolerance of investigational drugs. - Changes in Quality of Life at baseline, 4 and 12 weeks. - Change in RLS symptoms (RLS score) from baseline to week 12 in subjects with RLS symptoms at baseline. - Impact of study drug on ability to complete chemotherapy assessed as yes or no response at 24 weeks. - Impact of study drug on response to chemotherapy, assessed as complete remission, partial remission, stable remission and progressive disease as per the investigator discretion at 24 weeks. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time point(s) are specified in each secondary endpoint. |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Denmark |
Germany |
India |
Poland |
Russian Federation |
Spain |
Sweden |
United Kingdom |
United States |
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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
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The end of study is defined as the completion of the last subject's last visit in any participating centre. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |