Clinical trial NCT02940860: Iron Isomaltoside/Ferric Derisomaltose vs Iron Sucrose for Treatment of Iron Deficiency Anemia in Non-Dialysis-Dependent Chronic Kidney Disease
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Iron Deficiency Anaemia
Iron Deficiency Anemia
Chronic Kidney Disease
Keywords: Iron Deficiency Anaemia
Iron Deficiency Anemia
IDA
Chronic Kidney Disease
CKD
Iron isomaltoside
Ferric derisomaltose
Monofer
Monoferric
Monover
Monofar
Monoferro
Lead sponsor: Pharmacosmos A/S
Sponsor class: INDUSTRY
First posted: 2016-10-21
Enrollment: 1538
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Evaluation of 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria includes:

1. Men and women, ≥ 18 years
2. Hb ≤ 11 g/dL
3. 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
4. Screening s-ferritin ≤ 100 ng/mL, or ≤ 300 ng/mL if Transferrin Saturation (TSAT) ≤ 30 %
5. Either no Erythropoiesis Stimulating Agent (ESAs) or ESAs as a stable dose 4 weeks before randomisation
6. Willingness to participate and signing the informed consent form

Exclusion Criteria includes:

1. Anaemia predominantly caused by factors other than IDA
2. Hemochromatosis or other iron storage disorders
3. Previous serious hypersensitivity reactions to any IV iron compounds
4. Prior to screening or during the trial period; has or will be treated with a red blood cell transfusion, radiotherapy, and/or chemotherapy
5. Undergoing dialysis for treatment of CKD
6. Planned surgical procedure within the trial period
7. Decompensated liver cirrhosis or active hepatitis
8. Alcohol or drug abuse within the past 6 month.
9. Pregnant or nursing women.

Primary outcomes:
measure: Change in Hemoglobin (Hb) From Baseline to Week 8
timeFrame: Baseline to week 8
measure: Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions
timeFrame: Baseline to week 8
Secondary outcomes:
measure: Composite Cardiovascular Adverse Events (AEs)
timeFrame: Baseline, week 1, 2, and 8
measure: Time to First Composite Cardiovascular Safety AE
timeFrame: Baseline, week 1, 2, 4, and 8
measure: S-phosphate <2 mg/dL at Any Time From Baseline to Week 1, 2, 4, and 8
timeFrame: Baseline, week 1, 2, 4, and 8
measure: Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8
timeFrame: Baseline, week 1, 2, 4, and 8
measure: Time to Change in Hb Concentration ≥1 g/dL
timeFrame: Baseline, week 1, 2, 4, and 8
measure: Hb Concentration of >12 g/dL at Any Time From Week 1 to Week 8
timeFrame: Week 1 to week 8
measure: Hb Concentration Increase of ≥2 g/dL at Any Time From Week 1 to Week 8
timeFrame: Week 1 to week 8
measure: S-Ferritin Concentration of ≥100 ng/mL and Transferrin Saturation (TSAT) of 20-50% at Any Time From Week 1 to Week 8
timeFrame: Week 1 to week 8
measure: Change in Hb Concentration From Baseline to Week 1, 2, and 4
timeFrame: Baseline, week 1, 2, and 4
measure: Change in S-ferritin From Baseline to Weeks 1, 2, 4, and 8
timeFrame: Baseline, week 1, 2, 4, and 8
measure: Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8
timeFrame: Baseline, week 1, 2, 4, and 8
measure: Change in Concentration of S-iron From Baseline to Week 1, 2, 4, and 8
timeFrame: Baseline, week 1, 2, 4, and 8
measure: Change in Fatigue Symptoms From Baseline to Week 1, 2, and 8
timeFrame: Baseline, week 1, 2, and 8
measure: Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Cost of Public Transport/Taxi And Parking
timeFrame: Baseline
measure: Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Return Journey by Car
timeFrame: Baseline
measure: Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Time Spent on Visit/Helping on Visit
timeFrame: Baseline
measure: Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits
timeFrame: Baseline
measure: Health Care Resource Use Questionnaire
timeFrame: Baseline
Other outcomes:
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city: Fort Worth
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city: Greenville
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state: Texas
city: Houston
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city: Houston
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state: Texas
city: Houston
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state: Texas
city: Houston
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state: Texas
city: Houston
country: United States
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state: Texas
city: Houston
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state: Texas
city: Lufkin
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state: Texas
city: McKinney
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state: Texas
city: Pearland
country: United States
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state: Texas
city: San Antonio
country: United States
facility: Pharmacosmos Investigational Site1
state: Texas
city: San Antonio
country: United States
facility: Pharmacosmos Investigational Site2
state: Texas
city: Saint George
country: United States
facility: Pharmacosmos Investigational Site
state: Utah
city: Arlington
country: United States
facility: Pharmacosmos Investigational Site
state: Virginia
city: Fairfax
country: United States
facility: Pharmacosmos Investigational Site
state: Virginia
Study officials:
affiliation: Pharmacosmos A/S
name: Pharmacosmos A/S Clinical and Non-clinical Research
role: STUDY_DIRECTOR
References:
citation: Sunil Bhandari, Lars Lykke Thomsen. Single 1000 mg infusion of iron isomaltoside1000 single 1000 mg infusion of iron isomaltoside 1000 demonstrates a more rapid hemoglobin response and reduced risk of cardiovascular adverse events compared to multiple dose iron sucrose In patients with iron deficiency anemia and nondialysis-dependent CKD. Nephrology Dialysis Transplantation 34 (Supplement 1): i349-i350, 2019, https://academic.oup.com/ndt/article/34/Supplement_1/gfz101.SaO035/5515662
citation: Bhandari S, Kalra PA, Berkowitz M, Belo D, Thomsen LL, Wolf M. Safety and efficacy of iron isomaltoside 1000/ferric derisomaltose versus iron sucrose in patients with chronic kidney disease: the FERWON-NEPHRO randomized, open-label, comparative trial. Nephrol Dial Transplant. 2021 Jan 1;36(1):111-120. doi: 10.1093/ndt/gfaa011.