E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Iron deficiency anaemia due to inflammatory bowel disease |
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E.1.1.1 | Medical condition in easily understood language |
low red blood cell count (anaemia) caused by swelling in gut (known as inflammatory bowel disease) |
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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 | 20.0 |
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 |
To compare the incidence of hypophosphatemia (low phosphate levels in the blood) in participants with iron deficiency anaemia (low red blodd cell count caused by low iron levels) due to swelling in the gut (known as inflammatory bowel disease, IBD) treated with iron isomaltoside (Monofer®) or ferric carboxymaltose(Ferinject®) . |
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E.2.2 | Secondary objectives of the trial |
To compare the effects of iron isomaltoside (Monofer®) and ferric carboxymaltose (Ferinject®) treatment in participants with iron deficiency anaemia (IDA) due to inflammatory bowel disease (IBD).
Safety objectives were: • Incidence of severe hypophosphatemia (low phosphate levels in the blood) • Time with hypophosphatemia • Proportion of participants with hypophosphatemia at the last visit • Blood phosphate levels • Fractional phosphate levels in urine (wee) • Levels of intact Fibroblast Growth Factor 23 (iFGF23), C-terminal FGF23 (cFGF23) levels of vitamin D, Parathyroid Hormone (PTH) and ionized calcium • Adverse Events (AEs) and biochemical safety parameters • Clinical significant changes in vital signs (such as pulse rate and blood pressure), heart electrical activity (observed using an electrocardigram, ECG), and standard laboratory values
Efficacy objectives were blood levels of: • haemoglobin (Hb) • ferritin • Transferrin Saturation (TSAT).
Other objectives include |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants included: 1. are ≥ 18 years 2. have been diagnosed with IBD 3 have a hemoglobin (Hb) value < 13 g/dL 4. have a body weight ≥ 50 kg 5. have a serum ferritin value > 100 ng/mL 6. have an eGFR (estimated Glomerular filtration rate) of ≥ 65 mL/min/1.73 m2 7. have a serum phosphate value of > 2.5 mg/dL 8. are when oral iron preparations are ineffective or cannot be used or where there is a clinical need to deliver iron rapidly 9. have provided written informed consent to participate in the study
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E.4 | Principal exclusion criteria |
Exclusion criteria included: 1. Anaemia (low red blood cell count) mainly caused by factors other than inflammatory bowel disease (IDA) according to Investigator's judgment 2. Haemoglobin (Hb) ≥ 10 g/dL and body weight < 70 kg 3. Hemochromatosis or other iron storage disorders 4. Known hypersensitivity reaction to any component of iron isomaltoside or ferric carboxymaltose 5. Previous serious hypersensitivity reactions to any intravenous (IV) iron compounds 6.Treatment with IV iron, erythropoietin or erythropoietin-stimulation agents, red blood cell transfusion, radiotherapy, chemotherapy and/or an investigational drug within the last 30 days prior to screening 7. Planned surgery during the trial period 8.Alanine Aminotransferase (ALAT) and/or Aspartate Aminotransferase (ASAT) > 3 times upper limit of normal (e.g. decompensated liver cirrhosis or active hepatitis) 9. Surgery under general anaesthesia within the last 30 days prior to screening 10. Any non-viral infection within the last 30 days prior to screening 11. Alcohol or drug abuse within the past 6 months 12. Untreated hyperparathyroidism 13. Kidney transplantation 14. Conditions that interfere with the participant's ability to understand the requirements of the trial and/or presumable non-compliance 15. Any other laboratory abnormality, medical condition, or psychiatric disorders which, in the opinion of the Investigator, will put the participant’s disease management at risk or may result in the participants being unable to comply with the trial requirements 16. Pregnant or nursing women, and women of childbearing potential not using highly efficient contraception.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the incidence of hypophosphatemia (defined as serum phosphate < 2 mg/dL) at any time from Baseline to day 35. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
any time between Baseline and day 35 |
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E.5.2 | Secondary end point(s) |
secondary safety endpoints include: a. Incidence of hypophosphatemia b. Incidence of serum phosphate < 1.0 mg/dL c. Time with hypophosphatemia (i.e. time with serum phosphate < 2.0 mg/dL) d. Proportion of participants with hypophosphatemia e. changes in serum phosphate f. Fractional phosphate urinary excretion g. Change in iFGF23, cFGF23, vitamin D (25, 1.25, 24.25), parathyroid hormone (PTH), and ionized calcium h. Type and incidence of adverse events i. Serious or severe hypersensitivity j. Clinically significant changes in vital signs, ECG and laboratory values
Secondary efficacy endpoints include changes in: • Haemoglobin • Serum ferritin • Transferrin Saturation (TSAT) Secondary exploratory endpoints include changes in: 1. biochemical bone/muscle markers (serum N-terminal Propeptide of Type I Collagen (PINP), Carboxy-terminal Collagen Crosslinks (CTx), serum alkaline phosphatase (bone specific and total), and creatine kinase) 2. Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale 3. Short Form -36 quality of Life questionnaire 4. Visual Analogue Scale (VAS) for bone pain 5. grip strength (to test muscle strength) 6. upper and lower limb proximal muscle function measured by the "1 kg arm lift" test and the "30 sec chair stand" test. 7. respiratory muscles strength measured by Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP) 8. disease activity status using Harvey-Bradshaw Index for Crohn’s disease or Partial Mayo Score (excluding Endoscopy Sub-score) for ulcerative colitis
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary safety endpoints a) any time from Baseline to week 10 b) at any time from Baseline to day 35 c) end of study d) at day 35 e) from Baseline to day 1 and weeks 1, 2, 5, 6, 7, and 10 f) at day 1 and weeks 1, 2, 5, 6, 7, and 10 g) from Baseline to day 1 and weeks 1, 2, 5, 6, 7, and 10 h) after first dose till End of study i) after the first dose of treatment till End of study. J) Vital signs post-infusion at Baseline and week 5 (visit 6), ECG and laboratory values from Baseline to day 1 and weeks 1, 2, 5, 6, 7, and 10
Secondary efficacy endpoints -changes from Baseline to day 1 and weeks 1, 2, 5, 6, 7, and 10 Secondary exploratory endpoints: 1, 2, 3,4, 5, 6, 7 from Baseline to day 1 and weeks 1, 2, 5, 6, 7, and 10 8 - 8. from baseline to weeks 5 and 10 |
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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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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
| 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 1 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |