E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage 5 Chronic Kidney Disease on Dialysis Threapy (CKD5D) |
Dialyseterapi krævende kronisk nyresygdom |
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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 | 10038359 - Renal and urinary 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 |
To demonstrate that intravenous iron isomaltoside 1000 (Monofer®) is noninferior to IV iron sucrose determined as ability to maintain Hb in subjects with CKD5D who are on maintenance iron therapy. |
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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®) 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 assess 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 |
Subjects with a diagnosis of CKD-5D, in dialysis therapy for at least 90 days prior to inclusion, will be
included if they meet all of the following 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 10.0 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. Does 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. Does to be kept stable during the study
period). |
Forsøgspersoner, som er diagnosticeret med CKD-5D, og som har været i dialyse i mindst 90 dage inden inklusion, inkluderes, hvis de opfylder følgende kriterier:
1. Mænd og kvinder over 18 år.
2. Forsøgspersoner, som er diagnosticeret med CKD-5D, og som har været i hæmodialyse i mindst 90 dage.
3. Forventet levetid over 12 måneder efter den forsøgsansvarlige investigators vurdering
4. Forsøgspersonen er villig og i stand til at deltage efter afgivelse af informeret samtykke.
5. Hb-koncentrationer mellem 10,0 g/dl og 12,5 g/dl (inklusiv begge værdier) både ved screeningsbesøg 1a og 1b. (Der skal gå mindst 1 uge mellem screeningsbesøg 1a og 1b).
6. Serumferritin < 800 ng/ml.
7. Transferrinmætning < 35 %.
8. Forsøgspersoner, som har fået ESA-behandling ved stabil dosis i de sidste 4 uger inden screening (det er kun tilladt at have undladt at tage 1 dosis. Dosen skal være stabil gennem studiet).
9. Forsøgspersoner, som ikke har fået intravenøst jern eller gennemsnitligt højst 100 mg/uge i de sidste 4 uger (det er kun tilladt at have undladt at tage 1 dosis. Dosen skal være stabil gennem studiet). |
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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 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. |
Personer, der opfylder et eller flere af følgende kriterier, er uegnede til inklusion i forsøget:
1. Anæmi forårsaget primært af andre faktorer end nyrerelateret anæmi.
2. Jernoverbelastning eller forstyrrelser i jernudnyttelsen (f.eks. hæmokromatose og hæmosiderose).
3. Patienter, som aktuelt behandles med immunosuppresiva. (lav dosis steroider er tilladte gennem studiet, hvis dosis svarer til højest 10 mg prednisolone/dag eller ækvivalent. Hvis det er muligt, skal dosis være stabil gennem studiet).
4. Forskel på Hb ≥ 1,0 g/dl mellem screeningsbesøg 1a og 1b.
5. Multiple allergier i anamnesen.
6. Dekompenseret levercirrhose eller aktiv hepatitis [alaninaminotransferase (ALT) > 3 x normalværdien] eller hepatitis B eller C i anamnesen.
7. Aktive akutte eller kroniske infektioner (vurderet ved klinisk skøn), understøttet af leukocyttal (WBC) og C-reaktivt protein (CRP).
8. Rheumatoid arthritis med symptomer eller tegn på aktiv ledinflammation.
9. Patienten er gravid eller ammer. (For at udelukke graviditet skal kvinder være postmenopausale (mindst 12 måneder siden sidste menstruation) eller steriliseret eller, for fødedygtige kvinder, anvende en af følgende antikonceptionsmetoder i hele forsøgsperioden og i en periode efter forsøgets afslutning svarende til mindst 5 biologiske plasmahalveringstider af forsøgslægemidlet: P-piller, spiral, parenteral antikonception med depotvirkning (depotpræparat med gestagen), subdermalt implantat, vaginalring eller depotplastre).
10. Blodtransfusion inden for de sidste 12 uger.
11. Planlagt elektiv operation inden for de næste 8 uger.
12. Deltagelse i et andet klinisk forsøg inden for de sidste 30 dage eller i et tidsrum inden screeningen svarende til mindre end 5 halveringstider af det pågældende forsøgslægemiddel.
13. Ubehandlet B12-vitamin- eller folatmangel.
14. Enhver anden medicinsk tilstand, som efter den forsøgsansvarlige investigators skøn kan gøre forsøgspersonen uegnet til gennemførelse af forsøget eller udsætte forsøgspersonen for en potentiel risiko ved deltagelse. Som eksempler kan nævnes: ukontrolleret hypertension, ustabil iskæmisk hjertesygdom og ukontrolleret diabetes mellitus.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is:
1. Proportion of patients able to maintain haemoglobin between 10 and 12.5 g/dl (both values
included) at week 6. |
Forsøgets primære endpoint er:
1. Andel af patienter som kan opretholde et hæmoglobin niveau mellem 10 og 12.5 g/dl (inklusiv begge værdier) til uge 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) |
The secondary end points of the study are:
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). |
De sekundære endpoints er:
1. Ændring i Hb-koncentration fra baseline til uge 2, 4 og 6.
2. Sikkerhedsmæssige laboratorievurderinger ved baseline og efter 1, 2, 4 og 6 uger.
3. Ændring i koncentrationen af serumjern, TfS, serumferritin og retikulocytter fra baseline til uge 1, 2, 4 og 6.
4. Antallet af forsøgspersoner i hver randomiseringsgruppe, som udtræder af forsøget på grund af manglende respons eller intolerance over for forsøgslægemidlerne.
5. Ændring i total QoL-score (LASA) fra baseline til uge 4 og 6.
6. Ændring i RLS-symptoner (CH-RLS-score) fra baseline til uge 6 hos forsøgspersoner med RLS-symptomer ved baseline.
7. Antal forsøgspersoner, som får uønskede lægemiddelreaktioner, herunder uventede og alvorlige formodede lægemiddelreaktioner (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. from baseline and 1, 2, 4 and 6 weeks.
3. from baseline to week 1, 2, 4 and 6.
5. from baseline to week 4 and 6.
6. from baseline to week 6 |
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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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Switzerland |
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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Last visit of the last subject expected 1 November 2012 |
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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 | 1 |
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 | 1 |
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 |