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 | 14.1 |
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 |
|
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 | 10022974 |
E.1.2 | Term | Iron deficiency anemia |
E.1.2 | System Organ Class | 100000004851 |
|
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 |
1. Men and women, aged more than 18 years.
2. Participants 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 |
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 or active hepatitis (Alanine
Aminotransferase (ALT) > 3 times upper normal limit).
6. Active acute or chronic infections ((assessed by clinical judgment),
supplied with White Blood Cells (WBC) and C-Reactive Protein (CRP)).
7. Rheumatoid arthritis with symptoms or signs of active joint
inflammation.
8. 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).
9. Extensive active bleeding necessitating blood transfusion.
10. Planned elective surgery during the study.
11. Participation in any other clinical study within 3 months prior to
screening.
12. Known intolerance to oral iron treatment.
13. Untreated B12 or folate deficiency.
14. I.V. or oral iron treatment or blood transfusion within 4 weeks prior to screening visit.
15. ESA treatment within 8 weeks prior to screening visit.
16. Serum ferritin > 500 μg/L.
17. 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.
18. Body weight < 30 kilograms. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in Hb concentrations from baseline to week 4 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Number of subjects who have change in Hb concentration ≥ 1.0 g/dL
from baseline to week 2, 4 or 8.
2. Number of subjects who have change in Hb concentration ≥ 2.0 g/dL from baseline to week 2, 4, or 8.
3. Number of subjects who have Hb > 11 g/dl (6.80 mmol/L), have
serum ferritin (200-800μg/L) and have achieved Transferrin saturation
(TfS) (20-50 %) at weeks 2, 4 or 8.
4. Change in Hb concentration from baseline to week 2 and 8.
5. Change in concentrations of serum iron, serum ferritin, TfS and TIBC from baseline to week 1, 2, 4 and 8.
6. Number of subjects who discontinue study because of lack of response or need for blood transfusion or intolerance of investigational drugs.
7. Change in total QoL score (LASA) from baseline to week 4 and 8.
8. Change in eGFR from baseline to week 8.
9. Change in RLS symptoms (CH-RLSq score) from baseline to week 8 in subjects with RLS symptoms at baseline.
10. Number of subjects who experience any Adverse Drug Reaction (ADR) including any Suspected Unexpected Serious Adverse Reaction (SUSAR).
11. 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). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time point(s) are specified under each secondary endpoint. |
|
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 | 12 |
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 |
Ireland |
Poland |
Romania |
Russian Federation |
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 | 3 |
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 |