Iron Isomaltoside/Ferric Derisomaltose vs Iron Sucrose for Treatment of Iron Deficiency Anemia in Non-Dialysis-Dependent Chronic Kidney Disease
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| ClinicalTrials.gov Identifier: NCT02940860 |
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Recruitment Status :
Completed
First Posted : October 21, 2016
Results First Posted : March 6, 2020
Last Update Posted : October 6, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Iron Deficiency Anaemia Iron Deficiency Anemia Chronic Kidney Disease | Drug: Iron isomaltoside/ferric derisomaltose Drug: Iron sucrose | Phase 3 |
Iron deficiency anaemia (IDA) is a common problem associated with many chronic diseases such as chronic kidney disease (CKD). IDA can have a substantial medical and quality of life (QoL) burden on the subjects. Therapy of these subjects includes treating the underlying cause of IDA and restoring haemoglobin (Hb) concentration and iron stores.
This study evaluated the safety and efficacy of iron isomaltoside/ferric derisomaltose compared with iron sucrose in subjects with both non-dialysis-dependent chronic kidney disease (NDD-CKD) and iron deficiency anaemia (IDA).
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1538 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 Anaemia and Non-dialysis-dependent Chronic Kidney Disease (FERWON-NEPHRO) |
| Actual Study Start Date : | November 29, 2016 |
| Actual Primary Completion Date : | May 29, 2018 |
| Actual Study Completion Date : | May 29, 2018 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Iron isomaltoside/ferric derisomaltose
Administered IV
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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® |
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Active Comparator: Iron sucrose
Administered IV
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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® |
- Change in Hemoglobin (Hb) From Baseline to Week 8 [ Time Frame: Baseline to week 8 ]
Efficacy
Evaluate the effect of iron isomaltoside/ferric derisomaltose vs iron sucrose in subjects with non-dialysis-dependent chronic kidney disease (NDD-CKD) and 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 NDD-CKD and IDA, when oral iron preparations were ineffective or could not be used, or in whom the Hb measurement at screening in Investigators' opinion were sufficiently low to require rapid repletion of iron stores.
- 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.
- Composite Cardiovascular Adverse Events (AEs) [ Time Frame: Baseline, week 1, 2, and 8 ]
Safety
Results show the composite cardiovascular 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.
- 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.
- 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 participants who had s-phosphate <2 mg/dL at any time from baseline to week 1, 2, 4, or 8.
- Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8 [ Time Frame: Baseline, week 1, 2, 4, and 8 ]
Efficacy
Results show Hb responders to the treatment. A subject was considered a Hb responder to a certain week if an increase in Hb of at least 1 g/dL from baseline to the week in question was observed (from baseline to week 1, 2, 4, and 8).
- Time to Change in Hb Concentration ≥1 g/dL [ Time Frame: Baseline, week 1, 2, 4, and 8 ]
Efficacy
Time to change in Hb concentration ≥1 g/dL.
Subjects who showed Hb concentration increase of ≥1 g/dL (from baseline to week 1, 2, 4, and 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.
- 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.
- 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.
- 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.
- 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.
- Change in S-ferritin From Baseline to Weeks 1, 2, 4, and 8 [ Time Frame: Baseline, week 1, 2, 4, and 8 ]
Efficacy
Changes in s-ferritin from baseline to weeks 1, 2, 4, and 8.
- 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.
- Change in Concentration of 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.
- 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
- 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).
- 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).
- 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).
- 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).
- 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 2 treatment groups is different (i.e. up to a factor 5 more frequent in the iron sucrose treatment group).
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria includes:
- Men and women, ≥ 18 years
- Hb ≤ 11 g/dL
- Chronic renal impairment, as defined by either (i) eGFR < 60 mL/min/1.73m2 at screening (as calculated by modification of diet in renal disease (MDRD)), or (ii) Estimated Glomerular Filtration Rate (eGFR) < 90 mL/min/1.73m2 at screening and kidney damage as indicated by abnormalities in urine composition per medical history and/or intermediate/high risk of cardio-vascular disease based on the Framingham model
- Screening s-ferritin ≤ 100 ng/mL, or ≤ 300 ng/mL if Transferrin Saturation (TSAT) ≤ 30 %
- Either no Erythropoiesis Stimulating Agent (ESAs) or ESAs as a stable dose 4 weeks before randomisation
- Willingness to participate and signing the informed consent form
Exclusion Criteria includes:
- Anaemia predominantly caused by factors other than IDA
- Hemochromatosis or other iron storage disorders
- Previous serious hypersensitivity reactions to any IV iron compounds
- Prior to screening or during the trial period; has or will be treated with a red blood cell transfusion, radiotherapy, and/or chemotherapy
- Undergoing dialysis for treatment of CKD
- Planned surgical procedure within the trial period
- Decompensated liver cirrhosis or active hepatitis
- Alcohol or drug abuse within the past 6 month.
- Pregnant or nursing women.
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): NCT02940860
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| Study Director: | Pharmacosmos A/S Clinical and Non-clinical Research | Pharmacosmos A/S |
Documents provided by Pharmacosmos A/S:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Pharmacosmos A/S |
| ClinicalTrials.gov Identifier: | NCT02940860 |
| Other Study ID Numbers: |
P-Monofer-CKD-04 |
| First Posted: | October 21, 2016 Key Record Dates |
| Results First Posted: | March 6, 2020 |
| Last Update Posted: | October 6, 2020 |
| Last Verified: | February 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
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Iron Deficiency Anaemia Iron Deficiency Anemia IDA Chronic Kidney Disease CKD Iron isomaltoside |
Ferric derisomaltose Monofer Monoferric Monover Monofar Monoferro |
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Kidney Diseases Renal Insufficiency, Chronic Anemia Anemia, Iron-Deficiency Deficiency Diseases Hematologic Diseases Urologic Diseases Renal Insufficiency Anemia, Hypochromic Iron Metabolism Disorders |
Metabolic Diseases Malnutrition Nutrition Disorders Iron Ferric Oxide, Saccharated Iron isomaltoside 1000 Trace Elements Micronutrients Physiological Effects of Drugs Hematinics |