E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inflammatory Bowel Disease (IBD) |
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E.1.1.1 | Medical condition in easily understood language |
Inflammatory Bowel Disease (IBD) |
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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 | 10002062 |
E.1.2 | Term | Anaemia iron deficiency |
E.1.2 | System Organ Class | 100000004851 |
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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 evaluate the safety of a high IV iron dosing regimen of iron iso-maltoside 1000 in subjects with IDA secondary to IBD. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are:
• To evaluate the efficacy of a high IV iron dosing regimen of iron isomaltoside 1000
• To evaluate QoL and pharmacoeconomic parameters of a high IV iron dosing regimen of iron isomaltoside 1000.
In addition, the effect of iron isomaltoside 1000 on disease activity and FGF23 will be evaluated. However, these analyses will be purely exploratory.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects with age ≥ 18 years
2. Subjects diagnosed with IBD either in remission or active
3. Hb < 12 g/dL for women and Hb < 13 g/dL for men
4. Subjects with a CRP above upper limit of normality must have a ferritin below 100 µg/L, whereas subjects with a CRP below or equal to upper limit of normality must have a ferritin below 30 µg/L
5. Willingness to participate after signing informed consent
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E.4 | Principal exclusion criteria |
1. Patient judged by the physician to be in need of surgery due to Crohn's disease or ulcerative colitis within the next 2 months
2. Anaemia predominantly caused by factors other than IDA
3. Iron overload or disturbance in utilisation of iron (e.g. haemochromatosis and haemosiderosis)
4. Known hypersensitivity to any excipients of iron isomaltoside 1000
5. History of multiple allergies
6. Decompensated liver cirrhosis or active viral hepatitis (defined as Alanine Aminotransferase (ALAT) > 3 times upper limit of normal)
7. Acute and/or chronic infections
8. Body weight < 50 kg
9. Rheumatoid arthritis with symptoms or signs of active joint inflammation
10. Pregnancy and nursing. In order to avoid pregnancy, women have to be postmenopausal, surgically sterile, or use one of the following contraceptives during the whole study period and 5 days after the study has ended (i.e. 5 times plasma biological half-life of the investigational medicinal product): intrauterine devices and hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release)
11. Blood transfusion within the previous 12 weeks
12. Subjects with a history of asthma, allergic eczema, or other atopic allergy
13. Planned elective surgery during the study
14. Untreated Vitamin B12 or folate deficiency, defined as values below the lower reference range
15. Participation in any other clinical study within 3 months prior to Screening
16. IV iron treatment within 8 weeks prior to Screening
17. Oral iron treatment within 1 week prior to Screening
18. ESA treatment within 8 weeks prior to Screening
19. Any other medical condition that, in the opinion of 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the type and incidence of adverse drug reactions (ADRs). |
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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 safety endpoints are:
1. Number of adverse events (AEs) of special interest (i.e. hypersensitivity reactions or hypotension at pre-specified time points in relation to administration of study drug)
2. Change in complete blood count, s-sodium, s-potassium, s-calcium, s-phosphate, s-urea, s-creatinine, s-albumin, s-bilirubin, ASAT, and ALAT from Baseline to Week 1, 4, 8 in Treatment Group A and B or in Week 9, 12, 16 in Treatment Group B
3. Change in vital signs (pulse and blood pressure) from Baseline to Week 1, 4, 8 in Treatment Group A and B and to Week 9, 12, 16 in Treatment Group B
4. Change in electrocardiogram (ECG) from Baseline to Week 8 in Treatment Group A and to Week 16 in Treatment Group B
5. Change in weight from Baseline to Week 8 in Treatment Group A and to Week 16 in Treatment Group B
6. Change in physical condition from Screening to Week 8 in Treatment Group A and to Week 16 in Treatment Group B
The secondary efficacy endpoints are:
1. Number of subjects who obtain a target Hb (≥ 13 g/dL in men and ≥ 12g/dL in women) at Week 1, 4, 8 in Treatment Group A and B and at Week 9, 12, 16 in Treatment Group B
2. Number of subjects who have an increase in Hb concentration ≥ 2.0 g/dL from Baseline to Week 8 in Treatment Group A and B or to Week 16 in Treatment Group B
3. Number of subjects who have an increase in Hb concentration ≥ 1.0 g/dL from Baseline to Week 8 in Treatment Group A and B or to Week 16 in Treatment Group B
4. Time to obtain an increase in Hb concentration ≥1.0 g/dL or ≥ 2.0 g/dL
5. Change in Hb concentration from Baseline to Week 1, 4, 8 in Treatment Group A and B and to Week 9, 12, 16 in Treatment Group B
6. Change in concentrations of s-iron, s-ferritin, transferrin, TfS, reticulocytes, reticulocyte haemo-globin content (CHr), and soluble transferrin receptor (sTfR) from Baseline to Week 1, 4, 8 in Treatment Group A and B and to Week 9, 12, 16 in Treatment Group B
7. Change in QoL score (Short-form Health Survey 12 Version 2 (SF-12 V2) and Multidimensional Fatigue Inventory 20 (MFI-20) questionnaires) from Baseline to week 8 in Treatment Group A and B and to Week 16 in Treatment Group B
8. Change in subject related absence from work (Work Productivity and Activity Impairment (WPAI) questionnaire) from Baseline to week 8 in Treatment Group A and B and to Week 16 in Treatment Group B
9. Subject related travel time utilization and Willingness To Pay (WTP questionnaire) survey at Week 8
10. Health care related time utilization for treatment administration at Baseline in Treatment Group A and B
Exploratory Endpoints
1. Change in inflammatory parameters (C-reactive Protein (CRP), IL-6, TNF-alfa, and Hepcidin) from Baseline to Week 1, 4, 8 in Treatment Group A and B and to Week 9, 12, 16 in Treatment Group B
2. Change in faecal calprotectin from Baseline to Week 4 and 8 in Treatment Group A and B and to Week 16 in Treatment Group B
3. Change in FGF23 from Baseline to Week 1, 4, 8 in Treatment Group A and B and to Week 9, 12, 16 in Treatment Group B
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
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
| 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 | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |