Iron Isomaltoside/Ferric Derisomaltose vs Iron Sucrose for Treatment of Iron Deficiency Anemia in Non-Dialysis-Dependent Chronic Kidney Disease

Phase 3

Completed

• Conditions: Iron Deficiency Anemia; Iron Deficiency Anaemia; Chronic Kidney Disease
• Interventions: Drug: Iron isomaltoside/ferric derisomaltose; Drug: Iron sucrose

• Registration Number: NCT02940860
• Lead Sponsor: Pharmacosmos A/S

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.

Study Timeline

• Study First Submitted: 2016-09-27
• Study First Submitted QC: 2016-10-19
• Study First Posted: 2016-10-21
• Study Start: 2016-11-29
• Primary Completion: 2018-05-29
• Study Completion: 2018-05-29
• Disposition First Submitted: 2019-05-07
• Disposition First Submitted QC: 2019-05-07
• Disposition First Posted: 2019-05-13
• Status Verified: 2020-02
• Results First Submitted: 2020-02-04
• Results First Submitted QC: 2020-02-24
• Results First Posted: 2020-03-06
• Last Update Submitted: 2020-09-15
• Last Update Posted: 2020-10-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1538

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Iron isomaltoside/ferric derisomaltose	Iron isomaltoside/ferric derisomaltose	Administered IV
Iron sucrose	Iron sucrose	Administered IV

Primary Outcome Measures

Name	Time	Method
Change in Hemoglobin (Hb) From Baseline to Week 8	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	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

Name	Time	Method
Hb Concentration Increase of ≥1 g/dL From Baseline to Week 1, 2, 4, and 8	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).
Composite Cardiovascular Adverse Events (AEs)	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	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	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.
Time to Change in Hb Concentration ≥1 g/dL	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.
S-Ferritin Concentration of ≥100 ng/mL and Transferrin Saturation (TSAT) of 20-50% at Any Time From Week 1 to Week 8	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 S-ferritin From Baseline to Weeks 1, 2, 4, and 8	Baseline, week 1, 2, 4, and 8	Efficacy; Changes in s-ferritin from baseline to weeks 1, 2, 4, and 8.
Hb Concentration of >12 g/dL at Any Time From Week 1 to Week 8	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	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.
Change in Hb Concentration From Baseline to Week 1, 2, and 4	Baseline, week 1, 2, and 4	Efficacy; Change in Hb concentration from baseline to week 1, 2, and 4.
Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8	Baseline, week 1, 2, 4, and 8	Efficacy; Changes in transferrin saturation (TSAT) from baseline to week 1, 2, 4, and 8.
Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Time Spent on Visit/Helping on Visit	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).
Change in Concentration of S-iron From Baseline to Week 1, 2, 4, and 8	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.
Health Care Resource Use Questionnaire	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).
Change in Fatigue Symptoms From Baseline to Week 1, 2, and 8	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	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	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	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).

Trial Locations

Locations (4)

Pharmacosmos Investigational Site; 🇺🇸 Fairfax, Virginia, United States

Pharmacosmos Investigational Site1; 🇺🇸 San Antonio, Texas, United States

Pharmacosmos Investigational Site2; 🇺🇸 San Antonio, Texas, United States

Pharmacosmos Investigational Site3; 🇺🇸 Miami, Florida, United States