E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage 5 Chronic Kidney Disease on Dialysis Threapy (CKD-5D) |
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E.1.1.1 | Medical condition in easily understood language |
Stage 5 Chronic Kidney Disease on Dialysis Therapy (CKD-5D) |
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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 | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 100000004857 |
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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 demonstrate that intravenous iron isomaltoside 1000 (Monofer®) is non-inferior to IV iron sucrose determined as ability to maintain Hb in subjects with CKD-5D who are on maintenance iron therapy |
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E.2.2 | Secondary objectives of the trial |
• To obtain safety reassurance with the use of iron isomaltoside 1000 (Monofer®) for the maintenance of Haemoglobin in subjects with CKD-5D who are on maintenance iron therapy
• To evaluate the safety of intravenous iron isomaltoside 1000 (Monofer®) in comparison with iron sucrose administered intravenously in patients with CKD-5D
• To compare iron related hematological parameters (Haemoglobin (Hb), Transferrin Saturation (TfS), serum iron, serum ferritin levels and reticulocyte count)
• To evaluate the number of subjects who discontinue study due to lack of response or intolerance
• Assess changes in Quality of Life (QoL) by Linear Analog Scale Assessment (LASA)
• Assess Restless Legs Syndrome (RLS) symptoms and change in these symptoms during the study |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men or women, aged 18 years or greater.
2. Subjects diagnosed with CKD-5D and in haemodialysis therapy for at least 90 days.
3. Life expectancy beyond 12 months by Principal Investigator’s judgement.
4. Willingness and ability to participate after Informed Consent.
5. Hb concentrations between 9.5 g/dL and 12.5 g/dL (both values included) both at screening Visit 1a and at Screening Visit 1b. (Screening Visit 1a and Visit 1b must be separated by at least 1 week).
6. Serum ferritin < 800 ng/mL.
7. Transferrin Saturation < 35%.
8. Subjects receiving ESA treatment with dose stable for the previous 4 weeks prior to inclusion (with only 1 missed dose to be allowed. Dose to be kept stable during the study period).
9. Subjects receiving no IV iron or an average of no more than 100 mg/week for the previous 4 weeks (with only 1 missed dose to be allowed). |
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E.4 | Principal exclusion criteria |
1. Anaemia caused primarily by factors other than renal related anaemia.
2. Iron overload or disturbances in utilization of iron (e.g. haemochromatosis and haemosiderosis).
3. Patients currently undergoing treatment with immunosuppresives (low dose steroids are allowed during the study conduct for dosages no more than 10 mg prednisolone/day or equivalent. If possible the dosage should be kept constant through the study).
4. Difference of Hb 1.0 g/dL between screening Visits 1a and 1b.
5. Patients with a history of multiple allergies.
6. Decompensated liver cirrhosis or active hepatitis [Alanine Aminotransferase (ALT) > 3 times normal] or history of Hepatitis B or C.
7. Active acute or chronic infections (assessed by clinical judgement), supplied with White Blood Cells (WBC) and C-Reactive Protein (CRP).
8. Rheumatoid arthritis with symptoms or signs of active joint inflammation.
9. Pregnancy or 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).
10. Blood transfusion within the previous 12 weeks.
11. Planned elective surgery in the next 8 weeks.
12. Participation in any other clinical trial within the past 30 days, or if longer, where the study drug has not passed five half-lives prior to screening.
13. Untreated Vitamin B12 or folate deficiency.
14. 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. Examples include 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 6. |
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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) |
1. Change in Hb concentration from baseline to week 2, 4, and 6.
2. Safety laboratory assessments at baseline and 1, 2, 4 and 6 weeks.
3. Change in concentrations of serum iron, TfS, serum ferritin and reticulocyte count from baseline to week 1, 2, 4 and 6.
4. Number of subjects in each randomization group who discontinue study because of lack of response or intolerance of investigational drugs.
5. Change in total QoL score (LASA) from baseline to week 4 and 6.
6. Change in RLS symptoms (CH-RLSq score) from baseline to week 6 in subjects with RLS symptoms at baseline.
7. Number of subjects who experience any Adverse Drug Reaction (ADR) including any Suspected Unexpected Serious Adverse Reaction (SUSAR). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. from baseline to week 2, 4, and 6.
2. at baseline and 1, 2, 4 and 6 weeks.
3. from baseline to week 1, 2, 4 and 6.
4. all study
5. from baseline to week 4 and 6.
6. from baseline to week 6 in subjects with RLS symptoms at baseline.
7. all study |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
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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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Last Subject Last Visit is either the date of the last subject visit of the last subject to complete the study, or the date at which the last data point from the last subject, which was required for statistical analysis (i.e. key safety and efficacy results for decision making), was received, whichever is the later date. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |