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Iron Isomaltoside/Ferric Derisomaltose vs Iron Sucrose for the Treatment of Iron Deficiency Anemia (IDA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02940886
Recruitment Status : Completed
First Posted : October 21, 2016
Results First Posted : March 10, 2020
Last Update Posted : October 6, 2020
Sponsor:
Information provided by (Responsible Party):
Pharmacosmos A/S

Brief Summary:
Evaluate safety and efficacy of iron isomaltoside/ferric derisomaltose (Monofer®/Monoferric®) compared with iron sucrose (Venofer®), in subjects diagnosed with IDA.

Condition or disease Intervention/treatment Phase
Iron Deficiency Anaemia Iron Deficiency Anemia Drug: Iron isomaltoside/ferric derisomaltose Drug: Iron sucrose Phase 3

Detailed Description:

IDA is highly prevalent condition in subjects with cancer and gastrointestinal diseases such as inflammatory bowel diseases, menstruating or pregnant women, and subjects who have undergone bariatric procedure or surgery. IDA can have a substantial medical and quality of life (QoL) burden. Treatment of subjects diagnosed with IDA includes controlling the bleeding and replenishing lost iron.

This study was designed to evaluate the safety and efficacy of iron isomaltoside/ferric derisomaltose compared with iron sucrose in subjects diagnosed with IDA. In a subfraction of 35 subjects treated with iron isomaltoside/ferric derisomaltose, ECG and iron will be frequently measured.

The study subjects received either a single intravenous (IV) dose of iron isomaltoside/ferric derisomaltose (1000 mg at baseline) or iron sucrose (200 mg IV injections at baseline and repeated according to standard practice or physician choice up to a maximum of five times within the first two weeks starting at baseline; a cumulative dose of 1000 mg was recommended). The study subjects were monitored for up to 8 weeks from baseline.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1512 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Randomised, Open-label, Comparative Safety and Efficacy Trial of Intravenous Iron Isomaltoside/Ferric Derisomaltose (Monofer®/Monoferric®) and Iron Sucrose in Subjects With Iron Deficiency Anemia (FERWON-IDA)
Actual Study Start Date : November 8, 2016
Actual Primary Completion Date : March 28, 2018
Actual Study Completion Date : March 28, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia Iron

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 set to 1000 mg. The dose was diluted in 100 mL 0.9 % sodium chloride (100 mL bags) and administered as a single IV infusion over approximately 20 minutes.

Other Name: Monofer®, Monoferric®, Monover®, Monofar®, Monoferro®

Active Comparator: Iron sucrose
Administered IV
Drug: Iron sucrose

Iron sucrose (Venofer®; 20 mg elemental iron/mL) was the comparator in this trial.

Iron sucrose was administered as 200 mg undiluted IV injections over approximately 2-5 minutes and repeated according to standard practice or physician choice up to a maximum of five times within the first two weeks starting at baseline. A cumulative dose of 1000 mg was recommended.

Other Name: Venofer®




Primary Outcome Measures :
  1. Change in Hemoglobin (Hb) From Baseline to Week 8 [ Time Frame: Baseline to week 8 ]

    Efficacy

    Evaluate the effect on the hemoglobin (Hb) level following treatment with iron isomaltoside/ferric derisomaltose vs iron sucrose in subjects with iron deficiency anaemia (IDA) .

    Response was defined as change from baseline in hemoglobin (Hb) to week 8, i.e. ability to increase Hb in subjects with IDA, when oral iron preparations were ineffective or could not be used or in whom the screening Hb measurement in Investigators' opinion were sufficiently low to require rapid repletion of iron stores.


  2. Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions [ Time Frame: Baseline to week 8 ]

    Safety

    For this endpoint, the number of participants with serious or severe hypersensitivity reactions were evaluated. The hypersensitivity reactions that were included in the analysis were those that started on or after the first dose of randomised treatment (i.e. treatment emergent). The terms used to define hypersensitivity were those specified by the Standardised MedDRA Queries (SMQ) for hypersensitivity, plus four additional terms: loss of consciousness, seizure, syncope, unresponsiveness.

    The potential hypersensitivity AEs were adjudicated in a blinded fashion by an independent Clinical Endpoint Adjudication Committee (CEAC).

    Results show only those participants that had adjudicated and confirmed serious or severe hypersensitivity reactions.



Secondary Outcome Measures :
  1. Composite Cardiovascular Adverse Events (AEs) [ Time Frame: Baseline, week 1, 2, and 8 ]

    Safety

    Results show the composite cardiovascular adverse events (AEs), that started on or after the first dose of randomised treatment (i.e. treatment emergent) up to week 8.

    The reported potential cardiovascular AEs were adjudicated in a blinded fashion by an independent Clinical Endpoint Adjudication Committee (CEAC).

    The potential cardiovascular AEs included the following:

    • Death due to any cause
    • Non-fatal myocardial infarction
    • Non-fatal stroke
    • Unstable angina requiring hospitalisation
    • Congestive heart failure requiring hospitalisation or medical intervention
    • Arrhythmias
    • Hypertension
    • Hypotension

    Results show only those participants that had adjudicated and confirmed treatment-emergent composite cardiovascular AEs.


  2. Time to First Composite Cardiovascular Safety AE [ Time Frame: Baseline, week 1, 2, 4, and 8 ]

    Safety

    Time to first composite cardiovascular AE was defined as the actual time in days from first dose of treatment until the date of the composite cardiovascular AE. For subjects not reporting a composite cardiovascular AE, the time was censored at the date of the last attended visit. Only the adjudicated and confirmed composite cardiovascular safety AEs, as judged by the CEAC, were considered for this endpoint.

    Time to first composite cardiovascular AE was defined as the actual time in days from first dose of treatment until the date of the composite cardiovascular AE. For subjects not reporting a composite cardiovascular AE, the time was censored at the date of the last attended visit.


  3. S-phosphate <2 mg/dL at Any Time From Baseline to Week 1, 2, 4, and 8 [ Time Frame: Baseline, week 1, 2, 4, and 8 ]

    Safety

    Results show the number of subjects who had s-phosphate <2 mg/dL at any time from baseline to week 1, 2, 4, or 8.


  4. Hb Concentration Increase of ≥2 g/dL From Baseline to Week 1, 2, 4, and 8 [ Time Frame: Baseline, week 1, 2, 4, and 8 ]

    Efficacy

    Results show responders to the treatment. A subject was considered a Hb responder to a certain week if an increase in Hb of at least 2 g/dL from baseline to the week in question was observed (week 1, 2, 4, and 8).


  5. Time to Change in Hb Concentration ≥2 g/dL [ Time Frame: Baseline, week 1, 2, 4, and 8 ]

    Efficacy

    Time to change in Hb concentration ≥2 g/dL. Subjects who achieved Hb concentration increase of ≥2 g/dL (from baseline to week 1, 2, 4, or 8).

    For responders, time to Hb response was defined as the scheduled time from baseline until the visit where the first Hb response was measured.


  6. Hb Concentration of >12 g/dL at Any Time From Week 1 to Week 8 [ Time Frame: Week 1 to week 8 ]

    Efficacy

    Hb concentration of >12 g/dL at any time from week 1 to week 8.

    Results show the number of participants who achieved Hb concentration of >12 g/dL at any time from week 1 to week 8.


  7. Hb Concentration Increase of ≥2 g/dL at Any Time From Week 1 to Week 8 [ Time Frame: Week 1 to week 8 ]

    Efficacy

    Results show the number of participants who achieved Hb concentration increase of ≥2 g/dL at any time from week 1 to week 8.


  8. S-Ferritin Concentration of ≥100 ng/mL and Transferrin Saturation (TSAT) of 20-50% at Any Time From Week 1 to Week 8 [ Time Frame: Week 1 to week 8 ]

    Efficacy

    Proportion of subjects reaching the composite endpoint of s-ferritin concentration ≥100 ng/mL and TSAT of 20-50% at any time from week 1 to 8.


  9. Change in Hb Concentration From Baseline to Week 1, 2, and 4 [ Time Frame: Baseline, week 1, 2, and 4 ]

    Efficacy

    Change in Hb concentration from baseline to week 1, 2, and 4.


  10. Change in S-ferritin Concentration From Baseline to Weeks 1, 2, 4, and 8 [ Time Frame: Baseline, week 1, 2, 4, and 8 ]

    Efficacy

    Change in s-ferritin concentration from baseline to weeks 1, 2, 4, and 8.


  11. Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8 [ Time Frame: Baseline, week 1, 2, 4, and 8 ]

    Efficacy

    Changes in transferrin saturation (TSAT) from baseline to week 1, 2, 4, and 8.

    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.


  12. Change in Concentrations of Serum Iron (S-iron) From Baseline to Week 1, 2, 4, and 8 [ Time Frame: Baseline, week 1, 2, 4, and 8 ]

    Efficacy

    Changes in the concentrations of serum iron (s-iron) from baseline to week 1, 2, 4, and 8.


  13. Change in Fatigue Symptoms From Baseline to Week 1, 2, and 8 [ Time Frame: Baseline, week 1, 2, and 8 ]

    Efficacy

    Change in fatigue symptoms from baseline to week 1, 2, and 8 was measured by the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale.

    The Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale consisted of 13 items ranging from 0 (not at all) to 4 (very much), except items #7 and #8 which are reversed scored. The total score range is 0-52.

    A score of less than 30 indicated severe fatigue, and the higher the score, the better outcome/quality of life (QoL). If more than 50% of the items for a subject at a given visit were missing, the total score was not calculated.

    Total score was calculated as shown below:

    Total score= Sum of individual scores x 13 / Number of items answered


  14. Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Cost of Public Transport/Taxi And Parking [ Time Frame: Baseline ]

    Pharmacoeconomics

    The Intervals in Screening for Diabetic Retinopathy (ISDR) questionnaire at the baseline visit assessed the resources used by subjects to receive treatment. Resources used on other trial activities were not included. ISDR responses were summarised using descriptive statistics.

    The data for this endpoint show the responses at baseline for both treatment groups.

    The frequency of drug administration between the 2 treatment groups is different, however, (i.e. up to a factor 5 in the iron sucrose treatment group).


  15. Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Return Journey by Car [ Time Frame: Baseline ]

    Pharmacoeconomics

    The Intervals in Screening for Diabetic Retinopathy (ISDR) questionnaire at the baseline visit assessed the resources used by subjects to receive treatment. Resources used on other trial activities were not included. ISDR responses were summarised using descriptive statistics.

    The data for this endpoint show the responses at baseline for both treatment groups.

    The frequency of drug administration between the 2 treatment groups is different, however, (i.e. up to a factor 5 in the iron sucrose treatment group).


  16. Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Time Spent on Visit/Helping on Visit [ Time Frame: Baseline ]

    Pharmacoeconomics

    The Intervals in Screening for Diabetic Retinopathy (ISDR) questionnaire at the baseline visit assessed the resources used by subjects to receive treatment. Resources used on other trial activities were not included. ISDR responses were summarised using descriptive statistics.

    The data for this endpoint show the responses at baseline for both treatment groups.

    The frequency of drug administration between the 2 treatment groups is different, however, (i.e. up to a factor 5 in the iron sucrose treatment group).


  17. Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits [ Time Frame: Baseline ]

    Pharmacoeconomics

    The Intervals in Screening for Diabetic Retinopathy (ISDR) questionnaire at the baseline visit assessed the resources used by subjects to receive treatment. Resources used on other trial activities were not included. ISDR responses were summarised using descriptive statistics.

    The data for this endpoint show the responses at baseline for both treatment groups.

    The frequency of drug administration between the 2 treatment groups is different, however, (i.e. up to a factor 5 in the iron sucrose treatment group).


  18. Health Care Resource Use Questionnaire [ Time Frame: Baseline ]

    Pharmacoeconomics

    Resources used by the health care staff (per administration), measured by the health care resource use questionnaire. The questionnaire assessed the time used by the health care staff during administration of the investigational product and the administration time (including the observational time). The health care participants included in the evaluation were: investigator, pharmacist, physician, study coordinator, study nurse.

    The data for this endpoint show the responses at baseline for both treatment groups.

    The frequency of drug administration between the treatment groups is different (i.e. up to a factor 5 more frequent in the iron sucrose treatment group).




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria includes:

  1. Men or women ≥ 18 years
  2. Subjects having IDA caused by different etiologies
  3. Subjects with intolerance to oral iron therapy or a need for rapid repletion of iron stores:
  4. Haemoglobin (Hb) ≤ 11 g/dL
  5. Transferrin Saturation (TSAT) < 20 %
  6. S-ferritin < 100 ng/mL
  7. Willingness to participate and signing the informed consent form

Exclusion Criteria includes :

  1. Anemia predominantly caused by factors other than IDA
  2. Hemochromatosis or other iron storage disorders
  3. Previous serious hypersensitivity reactions to any IV iron compound
  4. Erythropoiesis stimulating agent (ESA) treatment
  5. Prior to screening or during the trial period; has or will be treated with a red blood cell transfusion, radiotherapy, and/or chemotherapy
  6. Will require a surgical procedure that necessitated general anesthesia prior to screening or during the trial period
  7. Alanine aminotransferase and/or aspartate aminotransferase > 3 times upper limit of normal
  8. Required dialysis for treatment of chronic kidney disease (CKD)
  9. Alcohol or drug abuse within the past 6 months
  10. Pregnant or nursing women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02940886


Locations
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Sponsors and Collaborators
Pharmacosmos A/S
Investigators
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Study Director: Pharmacosmos A/S Clinical and Non-clinical Research Pharmacosmos A/S
  Study Documents (Full-Text)

Documents provided by Pharmacosmos A/S:
Study Protocol  [PDF] June 14, 2017
Statistical Analysis Plan  [PDF] April 12, 2018

Additional Information:
Publications of Results:
Auerbach M and Lykke LL. A single infusion of iron isomaltoside 1000 allows a more rapid hemoglobin increment than multiple doses of iron sucrose with a similar safety profile in patients with iron deficiency anemia. Blood 2018 132:2334; doi: https://doi.org/10.1182/blood-2018-99-110199

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Responsible Party: Pharmacosmos A/S
ClinicalTrials.gov Identifier: NCT02940886    
Other Study ID Numbers: P-Monofer-IDA-03
First Posted: October 21, 2016    Key Record Dates
Results First Posted: March 10, 2020
Last Update Posted: October 6, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Pharmacosmos A/S:
Iron Deficiency Anaemia
Iron Deficiency Anemia
IDA
Intravenous iron replacement therapy
Iron isomaltoside
Ferric derisomaltose
Monofer
Monoferric
Monover
Monofar
Monoferro
Additional relevant MeSH terms:
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Anemia
Anemia, Iron-Deficiency
Deficiency Diseases
Hematologic Diseases
Anemia, Hypochromic
Iron Metabolism Disorders
Metabolic Diseases
Malnutrition
Nutrition Disorders
Iron
Ferric Oxide, Saccharated
Iron isomaltoside 1000
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Hematinics