Iron Isomaltoside/Ferric Derisomaltose vs Iron Sucrose for the Treatment of Iron Deficiency Anemia (IDA)

Iron Deficiency Anemia Clinical Trial

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 Anemia (FERWON-IDA)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02940886
• Other study ID #: P-Monofer-IDA-03
• Status: Completed
• Phase: Phase 3
• Start date: November 8, 2016
• Est. completion date: March 28, 2018

Study information

• Verified date: January 2020
• Source: Pharmacosmos A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluate safety and efficacy of iron isomaltoside/ferric derisomaltose (Monofer®/Monoferric®) compared with iron sucrose (Venofer®), in subjects diagnosed with IDA.

Description:

IDA is highly prevalent condition in subjects with cancer and gastrointestinal diseases such as inflammatory bowel diseases, menstruating or pregnant women, and subjects who have undergone bariatric procedure or surgery. IDA can have a substantial medical and quality of life (QoL) burden. Treatment of subjects diagnosed with IDA includes controlling the bleeding and replenishing lost iron.

This study was designed to evaluate the safety and efficacy of iron isomaltoside/ferric derisomaltose compared with iron sucrose in subjects diagnosed with IDA. In a subfraction of 35 subjects treated with iron isomaltoside/ferric derisomaltose, ECG and iron will be frequently measured.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1512
• Est. completion date: March 28, 2018
• Est. primary completion date: March 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria includes:

1. Men or women = 18 years

2. Subjects having IDA caused by different etiologies

3. Subjects with intolerance to oral iron therapy or a need for rapid repletion of iron stores:

4. Haemoglobin (Hb) = 11 g/dL

5. Transferrin Saturation (TSAT) < 20 %

6. S-ferritin < 100 ng/mL

7. Willingness to participate and signing the informed consent form

Exclusion Criteria includes :

1. Anemia predominantly caused by factors other than IDA

2. Hemochromatosis or other iron storage disorders

3. Previous serious hypersensitivity reactions to any IV iron compound

4. Erythropoiesis stimulating agent (ESA) treatment

5. Prior to screening or during the trial period; has or will be treated with a red blood cell transfusion, radiotherapy, and/or chemotherapy

6. Will require a surgical procedure that necessitated general anesthesia prior to screening or during the trial period

7. Alanine aminotransferase and/or aspartate aminotransferase > 3 times upper limit of normal

8. Required dialysis for treatment of chronic kidney disease (CKD)

9. Alcohol or drug abuse within the past 6 months

10. Pregnant or nursing women

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron-Deficiency
• Deficiency Diseases
• Iron Deficiency Anaemia
• Iron Deficiency Anemia

Intervention

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 (100 mL bags) and administered as a single IV infusion over approximately 20 minutes.
• Iron sucrose
Iron sucrose (Venofer®; 20 mg elemental iron/mL) was the comparator in this trial. Iron sucrose was administered as 200 mg undiluted IV injections over approximately 2-5 minutes 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.

Locations

Country	Name	City	State
United States	Pharmacosmos Investigational Site	Austin	Texas
United States	Pharmacosmos Investigational Site	Aventura	Florida
United States	Pharmacosmos Investigational Site	Baton Rouge	Louisiana
United States	Pharmacosmos Investigational Site	Baytown	Texas
United States	Pharmacosmos Investigational Site	Beaumont	Texas
United States	Pharmacosmos Investigational Site	Beavercreek	Ohio
United States	Pharmacosmos Investigational Site	Bethesda	Maryland
United States	Pharmacosmos Investigational Site	Birmingham	Alabama
United States	Pharmacosmos Investigational Site	Boynton Beach	Florida
United States	Pharmacosmos Investigational Site	Canton	Ohio
United States	Pharmacosmos Investigational Site	Centerville	Ohio
United States	Pharmacosmos Investigational Site	Champaign	Illinois
United States	Pharmacosmos Investigational Site	Chattanooga	Tennessee
United States	Pharmacosmos Investigational Site	Chesapeake	Virginia
United States	Pharmacosmos Investigational Site	Cincinnati	Ohio
United States	Pharmacosmos Investigational Site	Columbia	South Carolina
United States	Pharmacosmos Investigational Site	Columbus	Ohio
United States	Pharmacosmos Investigational Site	Corsicana	Texas
United States	Pharmacosmos Investigational Site	DeSoto	Texas
United States	Pharmacosmos Investigational Site	Doral	Florida
United States	Pharmacosmos Investigational Site 1	Doral	Florida
United States	Pharmacosmos Investigational Site 2	Doral	Florida
United States	Pharmacosmos Investigational Site	Dothan	Alabama
United States	Pharmacosmos Investigational Site 1	East Setauket	New York
United States	Pharmacosmos Investigational Site 2	East Setauket	New York
United States	Pharmacosmos Investigational Site	Fall River	Massachusetts
United States	Pharmacosmos Investigational Site	Florissant	Missouri
United States	Pharmacosmos Investigational Site	Foothill Ranch	California
United States	Pharmacosmos Investigational Site	Fort Lauderdale	Florida
United States	Pharmacosmos Investigational Site	Franklin	Tennessee
United States	Pharmacosmos Investigational Site	Grand Rapids	Michigan
United States	Pharmacosmos Investigational Site	Guntersville	Alabama
United States	Pharmacosmos Investigational Site	Hagerstown	Maryland
United States	Pharmacosmos Investigational Site	Hialeah	Florida
United States	Pharmacosmos Investigational Site	Hialeah	Florida
United States	Pharmacosmos Investigational Site	Hialeah	Florida
United States	Pharmacosmos Investigational Site	Hollywood	Florida
United States	Pharmacosmos Investigational Site	Houston	Texas
United States	Pharmacosmos Investigational Site	Houston	Texas
United States	Pharmacosmos Investigational Site	Houston	Texas
United States	Pharmacosmos Investigational Site	Jacksonville	Florida
United States	Pharmacosmos Investigational Site	Jenkintown	Pennsylvania
United States	Pharmacosmos Investigational Site	Joliet	Illinois
United States	Pharmacosmos Investigational Site	Kissimmee	Florida
United States	Pharmacosmos Investigational Site	Knoxville	Tennessee
United States	Pharmacosmos Investigational Site 1	La Mesa	California
United States	Pharmacosmos Investigational Site 2	La Mesa	California
United States	Pharmacosmos Investigational Site	Lake City	Florida
United States	Pharmacosmos Investigational Site	Lake Worth	Florida
United States	Pharmacosmos Investigational Site	Lake Worth	Florida
United States	Pharmacosmos Investigational Site	Las Vegas	Nevada
United States	Pharmacosmos Investigational Site	Little Rock	Arkansas
United States	Pharmacosmos Investigational Site	Little Rock	Arkansas
United States	Pharmacosmos Investigational Site	Long Beach	California
United States	Pharmacosmos Investigational Site	Marrero	Louisiana
United States	Pharmacosmos Investigational Site	McAllen	Texas
United States	Pharmacosmos Investigational Site	Memphis	Tennessee
United States	Pharmacosmos Investigational Site	Metairie	Louisiana
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site	Miami	Florida
United States	Pharmacosmos Investigational Site 1	Miami	Florida
United States	Pharmacosmos Investigational Site 2	Miami	Florida
United States	Pharmacosmos Investigational Site	Miami Lakes	Florida
United States	Pharmacosmos Investigational Site 1	Miami Lakes	Florida
United States	Pharmacosmos Investigational Site 2	Miami Lakes	Florida
United States	Pharmacosmos Investigational Site	Myrtle Beach	South Carolina
United States	Pharmacosmos Investigational Site 1	Naples	Florida
United States	Pharmacosmos Investigational Site 2	Naples	Florida
United States	Pharmacosmos Investigational Site	National City	California
United States	Pharmacosmos Investigational Site	Neptune	New Jersey
United States	Pharmacosmos Investigational Site	New Orleans	Louisiana
United States	Pharmacosmos Investigational Site	New York	New York
United States	Pharmacosmos Investigational Site	Norman	Oklahoma
United States	Pharmacosmos Investigational Site 1	Northridge	California
United States	Pharmacosmos Investigational Site 2	Northridge	California
United States	Pharmacosmos Investigational Site	Oceanside	California
United States	Pharmacosmos Investigational Site	Ogden	Utah
United States	Pharmacosmos Investigational Site	Omaha	Nebraska
United States	Pharmacosmos Investigational Site	Owensboro	Kentucky
United States	Pharmacosmos Investigational Site	Palmetto Bay	Florida
United States	Pharmacosmos Investigational Site	Palos Heights	Illinois
United States	Pharmacosmos Investigational Site	Phoenix	Arizona
United States	Pharmacosmos Investigational Site	Plainsboro	New Jersey
United States	Pharmacosmos Investigational Site	Plainville	Connecticut
United States	Pharmacosmos Investigational Site	Plantation	Florida
United States	Pharmacosmos Investigational Site	Quartz Hill	California
United States	Pharmacosmos Investigational Site	Rialto	California
United States	Pharmacosmos Investigational Site	Riverside	California
United States	Pharmacosmos Investigational Site	Saginaw	Michigan
United States	Pharmacosmos Investigational Site	San Antonio	Texas
United States	Pharmacosmos Investigational Site	San Antonio	Texas
United States	Pharmacosmos Investigational Site	San Diego	California
United States	Pharmacosmos Investigational Site	San Diego	California
United States	Pharmacosmos Investigational Site	San Marcos	California
United States	Pharmacosmos Investigational Site	Shreveport	Louisiana
United States	Pharmacosmos Investigational Site	Tacoma	Washington
United States	Pharmacosmos Investigational Site	Terre Haute	Indiana
United States	Pharmacosmos Investigational Site	Towson	Maryland
United States	Pharmacosmos Investigational Site	Troy	Michigan
United States	Pharmacosmos Investigational Site	Tulsa	Oklahoma
United States	Pharmacosmos Investigational Site	West Palm Beach	Florida
United States	Pharmacosmos Investigational Site	Whittier	California
United States	Pharmacosmos Investigational Site	Wichita	Kansas
United States	Pharmacosmos Investigational Site	Wilmington	North Carolina
United States	Pharmacosmos Investigational Site	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pharmacosmos A/S

Country where clinical trial is conducted

United States, 

References & Publications (2)

Auerbach M and Lykke LL. A single infusion of iron isomaltoside 1000 allows a more rapid hemoglobin increment than multiple doses of iron sucrose with a similar safety profile in patients with iron deficiency anemia. Blood 2018 132:2334; doi: https://doi.

Auerbach M, Henry D, Derman RJ, Achebe MM, Thomsen LL, Glaspy J. A prospective, multi-center, randomized comparison of iron isomaltoside 1000 versus iron sucrose in patients with iron deficiency anemia; the FERWON-IDA trial. Am J Hematol. 2019 Sep;94(9):1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Hemoglobin (Hb) From Baseline to Week 8	Efficacy; Evaluate the effect on the hemoglobin (Hb) level following treatment with iron isomaltoside/ferric derisomaltose vs iron sucrose in subjects with 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 IDA, when oral iron preparations were ineffective or could not be used or in whom the screening Hb measurement in Investigators' opinion were sufficiently low to require rapid repletion of iron stores.	Baseline to week 8
Primary	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 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.	Baseline to week 8
Secondary	Composite Cardiovascular Adverse Events (AEs)	Safety; Results show the composite cardiovascular adverse events (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.	Baseline, week 1, 2, and 8
Secondary	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 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 1, 2, 4, and 8
Secondary	S-phosphate <2 mg/dL at Any Time From Baseline to Week 1, 2, 4, and 8	Safety; Results show the number of subjects who had s-phosphate <2 mg/dL at any time from baseline to week 1, 2, 4, or 8.	Baseline, week 1, 2, 4, and 8
Secondary	Hb Concentration Increase of =2 g/dL From Baseline to Week 1, 2, 4, and 8	Efficacy; Results show responders to the treatment. A subject was considered a Hb responder to a certain week if an increase in Hb of at least 2 g/dL from baseline to the week in question was observed (week 1, 2, 4, and 8).	Baseline, week 1, 2, 4, and 8
Secondary	Time to Change in Hb Concentration =2 g/dL	Efficacy; Time to change in Hb concentration =2 g/dL. Subjects who achieved Hb concentration increase of =2 g/dL (from baseline to week 1, 2, 4, or 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.	Baseline, week 1, 2, 4, and 8
Secondary	Hb Concentration of >12 g/dL at Any Time From 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.	Week 1 to week 8
Secondary	Hb Concentration Increase of =2 g/dL at Any Time From 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.	Week 1 to week 8
Secondary	S-Ferritin Concentration of =100 ng/mL and Transferrin Saturation (TSAT) of 20-50% at Any Time From 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.	Week 1 to week 8
Secondary	Change in Hb Concentration From Baseline to Week 1, 2, and 4	Efficacy; Change in Hb concentration from baseline to week 1, 2, and 4.	Baseline, week 1, 2, and 4
Secondary	Change in S-ferritin Concentration From Baseline to Weeks 1, 2, 4, and 8	Efficacy; Change in s-ferritin concentration from baseline to weeks 1, 2, 4, and 8.	Baseline, week 1, 2, 4, and 8
Secondary	Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8	Efficacy; Changes in transferrin saturation (TSAT) from baseline to week 1, 2, 4, and 8.; 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 1, 2, 4, and 8
Secondary	Change in Concentrations of Serum Iron (S-iron) From Baseline to 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.	Baseline, week 1, 2, 4, and 8
Secondary	Change in Fatigue Symptoms From Baseline to 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	Baseline, week 1, 2, and 8
Secondary	Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Cost of Public Transport/Taxi And Parking	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).	Baseline
Secondary	Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Return Journey by Car	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).	Baseline
Secondary	Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Time Spent on Visit/Helping on Visit	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).	Baseline
Secondary	Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits	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).	Baseline
Secondary	Health Care Resource Use Questionnaire	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 treatment groups is different (i.e. up to a factor 5 more frequent in the iron sucrose treatment group).	Baseline

External Links

•   Efficacy and safety of a single infusion of iron isomaltoside/ferric derisomaltose versus multiple doses of iron sucrose
•   The FERWON-IDA trial; comparison of iron isomaltoside/ferric derisomaltose versus iron sucrose in patients with iron deficiency anemia