E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-dialysis dependent chronic kidney disease and with renal-related anaemia (NDD-CKD) |
|
E.1.1.1 | Medical condition in easily understood language |
Patient having anemia due to a chronic kidney disease. Patient is not depending on dialysis |
|
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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022974 |
E.1.2 | Term | Iron deficiency anemia |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
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 oral iron sulphate in
reducing Renal-Related Anaemia in NDD-CKD subjects, determined as ability to increase haemoglobin (Hb). |
|
E.2.2 | Secondary objectives of the trial |
1. To assess other relevant haematology and biochemical parameters during the study.
2. Quality of Life (QoL) assessment by Linear Analog Scale Assessment (LASA).
3. To assess safety of intravenous iron isomaltoside 1000 (Monofer®) compared to oral iron sulfate
4. Assessment of RLS symptoms and change in these symptoms during the study |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects with a diagnosis of Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD) associated
with renal-related anaemia will be included if they meet all of the following criteria:
1. Men and women, aged more than 18 years.
2. Subjects diagnosed with NDD-CKD with MDRD calculated eGFR between 15-59 mL/min.
3. Hb <11.0 g/dL (6.80 mmol/L).
4. Either or both of the following iron stores indicators below target [Serum ferritin < 200 ug/l and
Transferrin saturation (TfS) < 20%].
5. Life expectancy beyond 12 months by Principal Investigator‟s judgement.
6. Willingness to participate after informed consent and any authorization as required by local law
(e.g. Protected Health Information [PHI] for North America). |
|
E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Anaemia predominantly caused by factors other than renal impairment or iron deficiency
(according to Principal Investigator‟s judgment).
2. Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis and haemosiderosis).
3. Drug hypersensitivity (i.e. previous hypersensitivity to iron dextran or iron mono- or disaccharide
complexes or to iron sulphate or any excipients of the study drug).
4. Subjects with history of multiple allergies.
5. Decompensated liver cirrhosis and hepatitis (alanine aminotransferase (ALT) > 3 times upper
normal limit).
6. Diagnosis of Hepatitis B and/or C confirmed by appropriate lab test.
7. Active acute or chronic infections ((assessed by clinical judgment), supplied with White Blood
Cells (WBC) and C - Reactive protein (CRP)).
8. Rheumatoid arthritis with symptoms or signs of active joint inflammation.
9. 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 (5 days): Contraceptive pills, Intrauterine Devices (IUD), contraceptive depot injections
(prolonged-release gestagen), subdermal implantation, vaginal ring, and transdermal patches).
10. Extensive active bleeding necessitating blood transfusion.
11. Planned elective surgery during the study.
12. Participation in any other clinical study within 3 months prior to screening.
13. Known intolerance to oral iron treatment.
14. Untreated B12 or folate deficiency.
15. I.V. or oral iron treatment or blood transfusion within 4 weeks prior to screening visit.
16. ESA treatment within 8 weeks prior to screening visit.
17. Serum ferritin > 500 μg/L.
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 or interfere with study drug evaluation. Example, Uncontrolled Hypertension, Unstable
Ischemic Heart Disease or Uncontrolled Diabetes Mellitus.
19. Body weight < 30 kilograms.
20. History of immunodeficiency, including positive HIV test result. |
|
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 8. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Number of subjects who have change in Hb concentration > 1.0 g/dL from baseline to week 2,4 and 8.
Number of subjects who have Hb > 11g/dl (6.80 mmol/L), have serum ferritin (200-800 µg/L) and have achieved Transferrin saturation (Tfs) (20-50%) at weeks 2, 4 and 8. |
|
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.8.3 |
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 | 7 |
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 |
India |
Sweden |
United Kingdom |
|
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
|
Last Participant Last Visit is either the date of the last visit of the last participant to complete the study, or the date at which the last data point from the last participant, which was required for statistical analysis (i.e. key safety and efficacy results for decision making), was received, whichever is the later date. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |