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

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)

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).

Study Overview

• Status: Completed
• Conditions: Iron Deficiency Anemia; Iron Deficiency Anaemia
• Intervention / Treatment: Drug: Iron isomaltoside/ferric derisomaltose; Drug: Ferric carboxymaltose

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90036
      • Pharmacosmos Investigational Site
    • Sacramento, California, United States, 95831
      • Pharmacosmos Investigational Site
    • Santa Ana, California, United States, 92704
      • Pharmacosmos Investigational Site
  • Florida
    • Clearwater, Florida, United States, 33759
      • Pharmacosmos Investigational Site
    • Miami, Florida, United States, 33125
      • Pharmacosmos Investigational Site
    • Miami, Florida, United States, 33126
      • Pharmacosmos Investigational Site 1
    • Miami, Florida, United States, 33126
      • Pharmacosmos Investigational Site 2
    • Miami, Florida, United States, 33143
      • Pharmacosmos Investigational Site
    • Miami, Florida, United States, 33144
      • Pharmacosmos Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Pharmacosmos Investigational Site
  • Kansas
    • Wichita, Kansas, United States, 67206
      • Pharmacosmos Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70001
      • Pharmacosmos Investigational Site
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17605
      • Pharmacosmos Investigational Site
  • Texas
    • Houston, Texas, United States, 77024
      • Pharmacosmos Investigational Site
  • Utah
    • Orem, Utah, United States, 84058
      • Pharmacosmos Investigational Site
  • Virginia
    • Leesburg, Virginia, United States, 20176
      • Pharmacosmos Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iron isomaltoside/ferric derisomaltose; Administered IV	Drug: Iron isomaltoside/ferric derisomaltose; 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).; Other Names: Monofer®, Monoferric®, Monover®, Monofar®, Monoferro®
Active Comparator: Ferric carboxymaltose; Administered IV	Drug: Ferric carboxymaltose; 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).; Other Names: Injectafer®, Ferinject®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pharmacosmos A/S

Publications and helpful links

General Publications

• Wolf M, Rubin J, Achebe M, Econs M, Peacock M, Imel E, Thomsen L, Carpenter T, Weber T, Zoller H. Effects of iron isomaltoside versus ferric carboxymaltose on hormonal control of phosphate homeostasis: The PHOSPHARE-IDA04/05 randomized controlled trials. Journal of the Endocrine Society, Volume 3, Issue Supplement_1, April-May 2019, OR13-3, https://doi.org/10.1210/js.2019-OR13-3
• Wolf M, Rubin J, Achebe M, Econs MJ, Peacock M, Imel EA, Thomsen LL, Carpenter TO, Weber T, Brandenburg V, Zoller H. Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. JAMA. 2020 Feb 4;323(5):432-443. doi: 10.1001/jama.2019.22450.

Helpful Links

• Effects of iron isomaltoside/ferric derisomaltose versus ferric carboxymaltose on hormonal control of phosphate homeostasis

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2017
• Primary Completion (Actual): June 19, 2018
• Study Completion (Actual): June 19, 2018

Study Registration Dates

• First Submitted: July 6, 2017
• First Submitted That Met QC Criteria: August 1, 2017
• First Posted (Actual): August 3, 2017

Study Record Updates

• Last Update Posted (Actual): February 25, 2020
• Last Update Submitted That Met QC Criteria: February 24, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: IDA; Iron deficiency; Iron Deficiency Anemia; Hypophosphatemia; Ferric carboxymaltose; Iron Deficiency Anaemia; Intravenous iron replacement therapy; Iron isomaltoside; Ferric derisomaltose; Monofer; Monoferric; Monover; Monofar; Monoferro
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Nutrition Disorders; Anemia, Hypochromic; Iron Metabolism Disorders; Malnutrition; Phosphorus Metabolism Disorders; Anemia, Iron-Deficiency; Anemia; Hypophosphatemia; Deficiency Diseases; Hematinics; Iron isomaltoside 1000
• Other Study ID Numbers: P-Monofer-IDA-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No