Brief Summary
Evaluate safety and efficacy of iron isomaltoside/ferric derisomaltose (Monofer®/Monoferric®) compared with iron sucrose (Venofer®), in subjects diagnosed with IDA.
Brief Title
Iron Isomaltoside/Ferric Derisomaltose vs Iron Sucrose for the Treatment of Iron Deficiency Anemia (IDA)
Detailed 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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Iron Deficiency Anaemia
Iron Deficiency Anemia
Eligibility Criteria
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
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
Inclusion Criteria
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
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
Gender
All
Gender Based
false
Keywords
Iron Deficiency Anaemia
Iron Deficiency Anemia
IDA
Intravenous iron replacement therapy
Iron isomaltoside
Ferric derisomaltose
Monofer
Monoferric
Monover
Monofar
Monoferro
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02940886
Org Class
Industry
Org Full Name
Pharmacosmos A/S
Org Study Id
P-Monofer-IDA-03
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome Description
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.
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.
Outcome Measure
Change in Hemoglobin (Hb) From Baseline to Week 8
Outcome Time Frame
Baseline to week 8
Outcome Description
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.
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.
Outcome Measure
Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions
Outcome Time Frame
Baseline to week 8
Secondary Outcomes
Outcome Description
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.
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.
Outcome Time Frame
Baseline, week 1, 2, and 8
Outcome Measure
Composite Cardiovascular Adverse Events (AEs)
Outcome Description
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.
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.
Outcome Time Frame
Baseline, week 1, 2, 4, and 8
Outcome Measure
Time to First Composite Cardiovascular Safety AE
Outcome Description
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.
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.
Outcome Time Frame
Baseline, week 1, 2, 4, and 8
Outcome Measure
S-phosphate <2 mg/dL at Any Time From Baseline to Week 1, 2, 4, and 8
Outcome Description
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).
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).
Outcome Time Frame
Baseline, week 1, 2, 4, and 8
Outcome Measure
Hb Concentration Increase of ≥2 g/dL From Baseline to Week 1, 2, 4, and 8
Outcome Description
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.
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.
Outcome Time Frame
Baseline, week 1, 2, 4, and 8
Outcome Measure
Time to Change in Hb Concentration ≥2 g/dL
Outcome Description
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 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.
Outcome Time Frame
Week 1 to week 8
Outcome Measure
Hb Concentration of >12 g/dL at Any Time From Week 1 to Week 8
Outcome Description
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.
Results show the number of participants who achieved Hb concentration increase of ≥2 g/dL at any time from week 1 to week 8.
Outcome Time Frame
Week 1 to week 8
Outcome Measure
Hb Concentration Increase of ≥2 g/dL at Any Time From Week 1 to Week 8
Outcome Description
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.
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.
Outcome Time Frame
Week 1 to week 8
Outcome Measure
S-Ferritin Concentration of ≥100 ng/mL and Transferrin Saturation (TSAT) of 20-50% at Any Time From Week 1 to Week 8
Outcome Description
Efficacy
Change in Hb concentration from baseline to week 1, 2, and 4.
Change in Hb concentration from baseline to week 1, 2, and 4.
Outcome Time Frame
Baseline, week 1, 2, and 4
Outcome Measure
Change in Hb Concentration From Baseline to Week 1, 2, and 4
Outcome Description
Efficacy
Change in s-ferritin concentration from baseline to weeks 1, 2, 4, and 8.
Change in s-ferritin concentration from baseline to weeks 1, 2, 4, and 8.
Outcome Time Frame
Baseline, week 1, 2, 4, and 8
Outcome Measure
Change in S-ferritin Concentration From Baseline to Weeks 1, 2, 4, and 8
Outcome Description
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.
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.
Outcome Time Frame
Baseline, week 1, 2, 4, and 8
Outcome Measure
Change in Transferrin Saturation (TSAT) From Baseline to Week 1, 2, 4, and 8
Outcome Description
Efficacy
Changes in the concentrations of serum iron (s-iron) from baseline to week 1, 2, 4, and 8.
Changes in the concentrations of serum iron (s-iron) from baseline to week 1, 2, 4, and 8.
Outcome Time Frame
Baseline, week 1, 2, 4, and 8
Outcome Measure
Change in Concentrations of Serum Iron (S-iron) From Baseline to Week 1, 2, 4, and 8
Outcome Description
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
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
Outcome Time Frame
Baseline, week 1, 2, and 8
Outcome Measure
Change in Fatigue Symptoms From Baseline to Week 1, 2, and 8
Outcome Description
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).
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).
Outcome Time Frame
Baseline
Outcome Measure
Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Cost of Public Transport/Taxi And Parking
Outcome Description
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).
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).
Outcome Time Frame
Baseline
Outcome Measure
Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Return Journey by Car
Outcome Description
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).
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).
Outcome Time Frame
Baseline
Outcome Measure
Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Time Spent on Visit/Helping on Visit
Outcome Description
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).
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).
Outcome Time Frame
Baseline
Outcome Measure
Intervals in Screening for Diabetic Retinopathy (ISDR) Questionnaire, Participants/Others Who Took Time Off Work to Attend Visits
Outcome Description
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).
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).
Outcome Time Frame
Baseline
Outcome Measure
Health Care Resource Use Questionnaire
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Mark Chaitowitz
Investigator Email
machaito@montefiore.org
Investigator Phone