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

Phase 3

Completed

• Conditions: Iron Deficiency Anaemia; Iron Deficiency Anemia
• Interventions: Drug: Iron isomaltoside/ferric derisomaltose

• Registration Number: NCT02962648
• Lead Sponsor: Pharmacosmos A/S

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2016-11-09
• Study First Submitted QC: 2016-11-09
• Study First Posted: 2016-11-11
• Study Start: 2017-01-09
• Primary Completion: 2018-06-12
• Study Completion: 2018-06-12
• Disposition First Submitted: 2019-05-22
• Disposition First Submitted QC: 2019-05-22
• Disposition First Posted: 2019-05-31
• Status Verified: 2020-01
• Results First Submitted: 2020-01-31
• Results First Submitted QC: 2020-02-24
• Last Update Submitted: 2020-02-24
• Results First Posted: 2020-03-10
• Last Update Posted: 2020-03-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 103

Inclusion Criteria

1. Completed one of the lead-in trials
2. Randomised and dosed with iron isomaltoside/ferric derisomaltose in one of the lead-in trials.
3. Haemoglobin (Hb) of ≤ 11 g/dL
4. Screening serum ferritin (s-ferritin) ≤ 100 ng/mL, or ≤ 300 ng/mL if transferrin saturation (TSAT) ≤ 30 %
5. Willingness to participate and signing the informed consent form (ICF)

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Exclusion Criteria

1. Intravenous (IV) iron treatment between the lead-in trial and screening
2. 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
3. Received an investigational drug within 30 days of screening
4. Decompensated liver cirrhosis or active hepatitis
5. Pregnant or nursing women.
6. 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Adverse Drug Reactions (ADR)	Baseline to week 26	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions	Baseline to week 26	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.
Composite Cardiovascular Adverse Events (AEs)	Baseline to week 26	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.
Time to First Composite Cardiovascular Safety AE	Baseline, week 2, 13, and 26	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.
S-phosphate <2 mg/dL at Any Time From Baseline to Week 26	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.
Change in Hb From Baseline to Week 2, 13, and 26	Baseline, week 2, 13, and 26	Efficacy.; Change in Hb from baseline to week 2, 13, and 26.
Change in S-ferritin From Baseline to Week 2, 13, and 26	Baseline, week 2, 13, and 26	Efficacy.; Change in s-ferritin from baseline to week 2, 13, and 26.
Change in Transferrin Saturation (TSAT) From Baseline to Week 2, 13, and 26	Baseline, 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.
Change in S-iron From Baseline to Week 2, 13, and 26	Baseline, week 2, 13, and 26	Efficacy.; Change in s-iron from baseline to week 2, 13, and 26.

Trial Locations

Locations (3)

Pharmacosmos Investigational Site; 🇺🇸 Houston, Texas, United States

Pharmacosmos Investigational Site 1; 🇺🇸 San Antonio, Texas, United States

Pharmacosmos Investigational Site 2; 🇺🇸 San Antonio, Texas, United States