An Extension Trial to Assess the Safety of Re-dosing of Iron Isomaltoside/Ferric Derisomaltose (Monofer®/Monoferric®)

Study Overview
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Brief Summary
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Evaluate safety and efficacy of intravenous (IV) iron isomaltoside/ferric derisomaltose re-dosing, in subjects who were previously treated with iron isomaltoside/ferric derisomaltose.

Detailed Description
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Among the various formulations of parenteral iron that are currently available, iron isomaltoside/ferric derisomaltose may allow flexibility in terms of high and rapid dosing. Up to now, most clinical trials with intravenous (IV) iron treatment were of 4-12 weeks in duration; longer trials are warranted to follow-up on long-term safety. The aim of the trial was to evaluate the safety and efficacy of IV iron isomaltoside/ferric derisomaltose re-dosing in subjects who were previously treated with iron isomaltoside/ferric derisomaltose in lead-in trials. This was a 6-months extension trial lasting 26 weeks. Eligible subjects attended 5 visits: screening, baseline (subjects treated with a single IV dose of 1000 mg iron isomaltoside/ferric derisomaltose), and follow-up visits at week 2, 13, and 26 weeks after the IV dose, for safety and efficacy assessments.

Official Title
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An Open-label, Multicentre, Extension Trial to Assess the Safety of Re-dosing of Intravenous Iron Isomaltoside/Ferric Derisomaltose (Monofer®/Monoferric®)

Conditions
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Iron Deficiency Anemia, Iron Deficiency Anaemia

Intervention / Treatment
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* Drug: Iron isomaltoside/ferric derisomaltose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed one of the lead-in trials Randomised and dosed with iron isomaltoside/ferric derisomaltose in one of the lead-in trials. Haemoglobin (Hb) of ≤ 11 g/dL Screening serum ferritin (s-ferritin) ≤ 100 ng/mL, or ≤ 300 ng/mL if transferrin saturation (TSAT) ≤ 30 % Willingness to participate and signing the informed consent form (ICF) Exclusion Criteria: Intravenous (IV) iron treatment between the lead-in trial and screening During 30-day period prior to screening or during the trial period; has or will be treated with a red blood cell transfusion, radiotherapy, and/or chemotherapy Received an investigational drug within 30 days of screening Decompensated liver cirrhosis or active hepatitis Pregnant or nursing women. Any other laboratory abnormality, medical condition, or psychiatric disorders which, in the opinion of the Investigator, will put the subject's disease management at risk or may result in the subject being unable to comply with the trial requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iron isomaltoside/ferric derisomaltose<br>Administered IV | Drug: Iron isomaltoside/ferric derisomaltose<br>* 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 from the site's supply and administered over approximately 20 minutes using IV infusion.<br>* Other names: Monofer®, Monoferric®, Monover®, Monofar®, Monoferro®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Adverse Drug Reactions (ADR) | Safety Evaluate the number of subjects with adverse drug reactions (ADRs), defined as AEs that were assessed by the investigator as related or possible related to the investigational product. | Baseline to week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. The hypersensitivity terms that were included in the analysis were those that started or after the first dose of 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. | Baseline to week 26 | 
| Composite Cardiovascular Adverse Events (AEs) | Safety Results show the composite cardiovascular AEs, that started on or after the first dose of treatment (i.e. treatment emergent) up to month 6. 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. | Baseline to week 26 | 
| Time to First Composite Cardiovascular Safety AE | 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 Clinical Endpoint Adjudication Committee (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. | Baseline, week 2, 13, and 26 | 
| S-phosphate <2 mg/dL at Any Time From Baseline to Week 26 | Safety Results show the number of trial participants and their status of s-phosphate <2 mg/dL, at any time from baseline to week 26. | Baseline to week 26 | 
| Change in Hb From Baseline to Week 2, 13, and 26 | Efficacy. Change in Hb from baseline to week 2, 13, and 26. | Baseline, week 2, 13, and 26 | 
| Change in S-ferritin From Baseline to Week 2, 13, and 26 | Efficacy. Change in s-ferritin from baseline to week 2, 13, and 26. | Baseline, week 2, 13, and 26 | 
| Change in Transferrin Saturation (TSAT) From Baseline to Week 2, 13, and 26 | Efficacy Change in transferrin saturation (TSAT) from baseline to week 2, 13, and 26. 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, week 2, 13, and 26 | 
| Change in S-iron From Baseline to Week 2, 13, and 26 | Efficacy. Change in s-iron from baseline to week 2, 13, and 26. | Baseline, week 2, 13, and 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron Deficiency Anemia, Iron Deficiency Anaemia, IDA, Intravenous iron replacement therapy, Chronic Kidney Disease, CKD, Iron isomaltoside, Ferric derisomaltose, Monofer, Monoferric, Monover, Monofar, Monoferro