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

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

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

Study Overview

• Status: Completed
• Conditions: Iron Deficiency Anemia; Iron Deficiency Anaemia
• Intervention / Treatment: Drug: 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 Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91910
      • Pharmacosmos Investigational Site
    • La Mesa, California, United States, 91942
      • Pharmacosmos Investigational Site 1
    • La Mesa, California, United States, 91942
      • Pharmacosmos Investigational Site 2
    • Northridge, California, United States, 91324
      • Pharmacosmos Investigational Site
    • Porterville, California, United States, 93257
      • Pharmacosmos Investigational Site
  • Florida
    • Doral, Florida, United States, 33172
      • Pharmacosmos Investigational Site
    • Hialeah, Florida, United States, 33012
      • Pharmacosmos Investigational Site
    • Miami, Florida, United States, 33135
      • Pharmacosmos Investigational Site
    • Miami, Florida, United States, 33147
      • Pharmacosmos Investigational Site
    • Miami, Florida, United States, 33165
      • Pharmacosmos Investigational Site
    • Miami Lakes, Florida, United States, 33014
      • Pharmacosmos Investigational Site
    • West Palm Beach, Florida, United States, 33409
      • Pharmacosmos Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pharmacosmos Investigational Site
    • Metairie, Louisiana, United States, 70006
      • Pharmacosmos Investigational Site
    • New Orleans, Louisiana, United States, 70125
      • Pharmacosmos Investigational Site
    • Shreveport, Louisiana, United States, 71101
      • Pharmacosmos Investigational Site
  • New Jersey
    • Plainsboro, New Jersey, United States, 08536
      • Pharmacosmos Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Pharmacosmos Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Pharmacosmos Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • Pharmacosmos Investigational Site
    • San Antonio, Texas, United States, 78215
      • Pharmacosmos Investigational Site 1
    • San Antonio, Texas, United States, 78215
      • Pharmacosmos Investigational Site 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Iron isomaltoside/ferric derisomaltose; Administered IV

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 from the site's supply and administered over approximately 20 minutes using IV infusion.; Other Names: Monofer®, Monoferric®, Monover®, Monofar®, Monoferro®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pharmacosmos A/S

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2017
• Primary Completion (Actual): June 12, 2018
• Study Completion (Actual): June 12, 2018

Study Registration Dates

• First Submitted: November 9, 2016
• First Submitted That Met QC Criteria: November 9, 2016
• First Posted (Estimate): November 11, 2016

Study Record Updates

• Last Update Posted (Actual): March 10, 2020
• Last Update Submitted That Met QC Criteria: February 24, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; CKD; IDA; Iron Deficiency Anemia; Iron Deficiency Anaemia; Intravenous iron replacement therapy; Iron isomaltoside; Ferric derisomaltose; Monofer; Monoferric; Monover; Monofar; Monoferro
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Nutrition Disorders; Anemia, Hypochromic; Iron Metabolism Disorders; Malnutrition; Anemia, Iron-Deficiency; Anemia; Deficiency Diseases; Hematinics; Iron isomaltoside 1000
• Other Study ID Numbers: P-Monofer-IDA/CKD-EXT-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No