Incidence of Hypophosphatemia After Treatment With Iron Isomaltoside/Ferric Derisomaltose vs Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia

Study Overview
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Brief Summary
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The trial was designed to evaluate the incidence of unintended hypophosphatemia (low level of phosphate in the blood) in subjects with iron deficiency anaemia (IDA).

Detailed Description
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This trial was designed to evaluate the effect of IV iron isomaltoside/ferric derisomaltose compared with IV ferric carboxymaltose on s-phosphate in subjects with IDA caused by different etiologies. The subjects received either a single intravenous (IV) dose of iron isomaltoside/ferric derisomaltose (1000 mg at baseline) or two IV doses of ferric carboxymaltose (one dose 750 mg at baseline and a second dose 750 mg on day 7; cumulative dose: 1500 mg). The study subjects were monitored for up to 35 days from baseline.

Official Title
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A Randomized, Open-label, Comparative Trial Comparing the Incidence of Hypophosphatemia in Relation to Treatment With Iron Isomaltoside/Ferric Derisomaltose and Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia (Phosphare-IDA-04)

Conditions
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Iron Deficiency Anaemia, Iron Deficiency Anemia

Intervention / Treatment
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* Drug: Iron isomaltoside/ferric derisomaltose
* Drug: Ferric carboxymaltose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria include: Subjects diagnosed with IDA, caused by different aetiologies Haemoglobin (Hb) ≤ 11 g/dL Body weight > 50 kg Serum ferritin (S-ferritin) < 100 ng/mL Estimated glomerular filtration rate (eGFR) ≥ 65 mL/min/1.73 m2 Serum phosphate (S-phosphate) > 2.5 mg/dL Intolerance or unresponsiveness to oral iron Willingness to participate and signing the Informed Consent Form (ICF) Exclusion Criteria include: Acute bleeding > 500 mL within 72 hours Anaemia predominantly caused by factors other than IDA Hemochromatosis or other iron storage disorders Previous serious hypersensitivity reactions to any IV iron compounds Treatment with IV iron within the last 30 days prior to screening Treatment with erythropoietin or erythropoietin-stimulation agents Red blood cell transfusion, radiotherapy, and/or chemotherapy Received an investigational drug within the last 30 days prior to screening Planned surgical procedure within the trial period Hepatic enzymes > 3 times upper limit of normal Surgery under anaesthetic within the last 30 days prior to screening Any non-viral infection within the last 30 days prior to screening Alcohol or drug abuse within the past 6 months Vitamin D deficiency Untreated hyperparathyroidism Kidney transplantation Active malignant disease, disease-free for less than 5 years History of a psychological illness or seizures Pregnant or nursing women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iron isomaltoside/ferric derisomaltose<br>Administered IV | Drug: Iron isomaltoside/ferric derisomaltose<br>* Iron isomaltoside/ferric derisomaltose (Monofer®/Monoferric®; 100 mg/mL) was the test product in this trial. The dose of iron isomaltoside/ferric derisomaltose for the individual subject was a single IV infusion of 1000 mg (10 mL containing 1000 mg iron isomaltoside/ferric derisomaltose diluted in 100 mL 0.9 % sodium chloride), given over approximately 20 minutes (50 mg iron/min) at baseline (cumulative dose: 1000 mg).<br>* Other names: Monofer®, Monoferric®, Monover®, Monofar®, Monoferro®;|
| Active Comparator: Ferric carboxymaltose<br>Administered IV | Drug: Ferric carboxymaltose<br>* Ferric carboxymaltose (Injectafer®; 50 mg/mL) was the comparator in this trial. Ferric carboxymaltose was administered as 750 mg, infused over at least 15 minutes at baseline and on day 7 (cumulative dose: 1500 mg).<br>* Other names: Injectafer®, Ferinject®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Hypophosphatemia (S-phosphate Level <2 mg/dL) | Safety The incidence of hypophosphatemia (defined as s-phosphate <2 mg/dL) at any time from baseline up to day 35. | Baseline to day 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time With Hypophosphatemia ( S-phosphate Level <2.0 mg/dL) | Safety Time with hypophosphatemia (i.e. time with s-phosphate level < 2.0 mg/dL) from baseline up to day 35. The time with hypophosphatemia was calculated as the actual number of days from the first day where s-phosphate was <2 mg/dL until the first day when s-phosphate was ≥2 mg/dL. If the subject did not reach s-phosphate ≥2 mg/dL, the subject was regarded as censored on day 35. | Baseline to day 35 | 
| Proportion of Subjects With Hypophosphatemia on Day 35 ( S-phosphate Level <2.0 mg/dL) | Safety Evaluate the proportion of subjects with hypophosphatemia (s-phosphate level <2.0 mg/dL) on day 35. | Baseline to day 35 | 
| Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Safety Absolute [∆] changes in s-phosphate from baseline to day 1, 7, 8, 14, 21, and 35. | Baseline, days 1, 7, 8, 14, 21, and 35 | 
| Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35 | Safety Relative [%] changes in s-phosphate from baseline to day 1, 7, 8, 14, 21, and 35. | Baseline, days 1, 7, 8, 14, 21, and 35 | 
| Change From Baseline in Fractional Phosphate Urinary Excretion | Safety Change in absolute fractional phosphate urinary excretion from baseline to days 1, 7, 8, 14, 21, and 35. Fractional excretion of phosphate (FEPi) is calculated as ([phosphate in urine X creatinine in serum]/[phosphate in serum X creatinine in urine]) X 100, and the unit is %. | Baseline, days 1, 7, 8, 14, 21, and 35 | 
| Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35 | Safety Change in concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) from baseline to day 1, 7, 8, 14, 21, and 35. | Baseline, days 1, 7, 8, 14, 21, and 35 | 
| Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Safety Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) from baseline to days 1, 7, 8, 14, 21, and 35. | Baseline, days 1, 7, 8, 14, 21, and 35 | 
| Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Safety Change in vitamin 25-Hydroxyvitamin D (vitamin D 25) from baseline to days 1, 7, 8, 14, 21, and 35. | Baseline, days 1, 7, 8, 14, 21, and 35 | 
| Change in 1,25-Dihydroxyvitamin D (Vitamin D 1.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Safety Change in 1,25-Dihydroxyvitamin D (vitamin D 1.25) from baseline to days 1, 7, 8, 14, 21, and 35. | Baseline, days 1, 7, 8, 14, 21, and 35 | 
| Change in 24,25-Dihydroxyvitamin D (Vitamin D 24.25) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Safety Change in 24,25-Dihydroxyvitamin D (vitamin D 24.25) from baseline to days 1, 7, 8, 14, 21, and 35 | Baseline, days 1, 7, 8, 14, 21, and 35 | 
| Change in Intact Parathyroid Hormone (PTH) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Safety Change in intact Parathyroid hormone (PTH) from baseline to days 1, 7, 8, 14, 21, and 35. | Baseline, days 1, 7, 8, 14, 21, and 35 | 
| Change in Ionized Calcium From Baseline to Days 1, 7, 8, 14, 21, and 35 | Safety Change in ionized calcium from baseline to days 1, 7, 8, 14, 21, and 35. | Baseline, days 1, 7, 8, 14, 21, and 35 | 
| Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions | Safety For this endpoint, the number of participants with serious or severe hypersensitivity reactions were evaluated. | Baseline to day 35 | 
| Change in Hemoglobin (Hb) Per Gram Iron From Baseline to Days 1, 7, 8, 14, 21, and 35 | Efficacy Change in hemoglobin (Hb) per gram iron from baseline to days 1, 7, 8, 14, 21, and 35. | Baseline, days 1, 7, 8, 14, 21, and 35 | 
| Change in S-ferritin From Baseline to Days 1, 7, 8, 14, 21, and 35 | Efficacy Change in s-ferritin from baseline to days 1, 7, 8, 14, 21, and 35. | Baseline, days 1, 7, 8, 14, 21, and 35 | 
| Change in Transferrin Saturation (TSAT) From Baseline to Days 1, 7, 8, 14, 21, and 35 | Efficacy Change in Transferrin Saturation (TSAT) from baseline to days 1, 7, 8, 14, 21, and 35. TSAT is the value of serum iron divided by the total iron-binding capacity and the unit is %, which referrers to % of iron-binding sites of transferrin being occupied by iron. | Baseline, days 1, 7, 8, 14, 21, and 35 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron Deficiency Anaemia, Iron Deficiency Anemia, IDA, Intravenous iron replacement therapy, Iron deficiency, Iron isomaltoside, Ferric derisomaltose, Monofer, Monoferric, Monover, Monofar, Monoferro, Hypophosphatemia, Ferric carboxymaltose