Iron Deficiency Anemia
Conditions
Keywords
iron deficiency anemia, IDA, ferumoxytol, ferric carboxymaltose, FCM, Injectafer, Feraheme, Ferinject
Brief summary
To evaluate the safety of 1.020 grams (g) of intravenous (IV) ferumoxytol compared to 1.500 g of IV ferric carboxymaltose (FCM).
Interventions
DRUGFerumoxytol
DRUGFCM
Sponsors
AMAG Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria include: * Participants with IDA and in whom IV iron treatment is indicated and defined as: * Participants with documented hemoglobin \<12.0 g per deciliter (dL) for females and \<14.0 g/dL for males within 60 days of dosing And * Participants with documented transferrin saturation (TSAT) ≤20% or Ferritin ≤100 nanograms (ng) per mL within 60 days of dosing * Documented history of unsatisfactory oral iron therapy or in whom oral iron cannot be tolerated, or for whom oral iron is considered medically inappropriate (as per oral iron history questionnaire) * All participants (male and female) of childbearing potential who are sexually active who agree to routinely use adequate contraception from randomization throughout the duration of the study Key
Exclusion criteria
include: * Known hypersensitivity reaction to any component of ferumoxytol or FCM * History of allergy to an IV iron * History of multiple drug allergies * Participants with dialysis-dependent chronic kidney disease * Hemoglobin ≤7.0 g/dL * Female participants who are pregnant, intend to become pregnant, are breastfeeding, have a positive serum/urine pregnancy test or not willing to use effective contraceptive precautions during the study (including females of childbearing potential who are partners of male participants)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Day 1 (after first dosing) through Week 5 | All IV iron formulations carry some risk of serious hypersensitivity reactions or anaphylaxis. Signs and symptoms potentially representing hypersensitivity were recorded and adjudicated by a blinded Clinical Events Committee (CEC). Hypotension is defined as a \>30% drop in systolic blood pressure from baseline or decrease of \>20 mmHg for systolic blood pressure. Statistical analysis was only performed on composite data. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Day 1 (after first dosing) through Week 5 | All IV iron formulations carry some risk of serious hypersensitivity reactions or anaphylaxis. Signs and symptoms potentially representing hypersensitivity were recorded and adjudicated by a blinded Clinical Events Committee (CEC). A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Mean Change In Hemoglobin From Baseline To Week 5 | Baseline (Day 1), Week 5 | Mean change in hemoglobin from Baseline to Week 5 was calculated for each participant as: Hemoglobin Change = Hemoglobin (Week 5) - Hemoglobin (Baseline). Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. |
| Mean Change In Hemoglobin Per Gram Of Iron Administered From Baseline To Week 5 | Baseline (Day 1), Week 5 | Mean change in hemoglobin per g of iron administered from Baseline (Day 1) to Week 5 was calculated for each participant as: Hemoglobin Change = Hemoglobin (Week 5) - Hemoglobin (Baseline). Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. |
Countries
Canada, Hungary, Latvia, Lithuania, Poland, Puerto Rico, United States
Participant flow
Recruitment details
Participants with iron deficiency anemia (IDA), \<12.0 grams (g) per deciliter (dL) for females and \<14.0 g/dL for males within 60 days of dosing and transferrin saturation (TSAT) \<20% or Ferritin ≤100 nanograms (ng) per milliliter (mL) within 60 days of dosing and a history of unsatisfactory oral iron therapy or in whom oral iron could not be used.
Participants by arm
| Arm | Count |
|---|---|
| Ferumoxytol Participants received an IV infusion of ferumoxytol 510 mg diluted (17 mL) in 233 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.020 g. | 997 |
| Ferric Carboxymaltose (FCM) Participants received an IV infusion of FCM 750 mg diluted (15 mL) in 235 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.500 g. | 1,000 |
| Total | 1,997 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 9 |
| Overall Study | Death | 4 | 1 |
| Overall Study | Lost to Follow-up | 14 | 17 |
| Overall Study | Other-Decision of Participant | 6 | 1 |
| Overall Study | Other-Investigator's decision | 1 | 0 |
| Overall Study | Other-Personal reasons | 3 | 3 |
| Overall Study | Other-Protocol noncompliant | 2 | 1 |
| Overall Study | Other-Unable to be reached | 0 | 1 |
| Overall Study | Other-Withdrew prior to dosing | 9 | 8 |
| Overall Study | Withdrawal by Subject | 22 | 19 |
Baseline characteristics
| Characteristic | Ferumoxytol | Ferric Carboxymaltose (FCM) | Total |
|---|---|---|---|
| Age, Continuous | 55.6 years STANDARD_DEVIATION 17.3 | 54.8 years STANDARD_DEVIATION 17.02 | 55.2 years STANDARD_DEVIATION 17.16 |
| Sex: Female, Male Female | 743 Participants | 776 Participants | 1519 Participants |
| Sex: Female, Male Male | 254 Participants | 224 Participants | 478 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 186 / 997 | 245 / 1,000 |
| serious Total, serious adverse events | 36 / 997 | 35 / 1,000 |
Outcome results
Primary
Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension
All IV iron formulations carry some risk of serious hypersensitivity reactions or anaphylaxis. Signs and symptoms potentially representing hypersensitivity were recorded and adjudicated by a blinded Clinical Events Committee (CEC). Hypotension is defined as a \>30% drop in systolic blood pressure from baseline or decrease of \>20 mmHg for systolic blood pressure. Statistical analysis was only performed on composite data. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Day 1 (after first dosing) through Week 5
Population: The safety population included any randomized participant who received any amount of study drug. Treatment group was based on actual treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ferumoxytol | Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Severe hypotension | 0 Participants |
| Ferumoxytol | Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Moderate hypersensitivity reaction | 3 Participants |
| Ferumoxytol | Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Moderate hypotension | 2 Participants |
| Ferumoxytol | Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Severe hypersensitivity reaction | 1 Participants |
| Ferumoxytol | Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Any TE moderate to severe hypersensitivity rxn | 6 Participants |
| Ferumoxytol | Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Anaphylaxis | 0 Participants |
| Ferric Carboxymaltose (FCM) | Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Any TE moderate to severe hypersensitivity rxn | 7 Participants |
| Ferric Carboxymaltose (FCM) | Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Moderate hypotension | 1 Participants |
| Ferric Carboxymaltose (FCM) | Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Severe hypotension | 0 Participants |
| Ferric Carboxymaltose (FCM) | Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Anaphylaxis | 0 Participants |
| Ferric Carboxymaltose (FCM) | Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Moderate hypersensitivity reaction | 6 Participants |
| Ferric Carboxymaltose (FCM) | Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension | Severe hypersensitivity reaction | 0 Participants |
Comparison: Statistical analysis was only performed on composite reaction data (that is, the Any TE moderate to severe hypersensitivity rxn row in the data table).p-value: 0.000195% CI: [-0.8, 0.61]Wald
Secondary
Mean Change In Hemoglobin From Baseline To Week 5
Mean change in hemoglobin from Baseline to Week 5 was calculated for each participant as: Hemoglobin Change = Hemoglobin (Week 5) - Hemoglobin (Baseline). Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information.
Time frame: Baseline (Day 1), Week 5
Population: Intent-to-treat (ITT) population: any randomized participant who had any exposure to study drug, based on randomized treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol | Mean Change In Hemoglobin From Baseline To Week 5 | 1.38 g/dL | Standard Deviation 1.351 |
| Ferric Carboxymaltose (FCM) | Mean Change In Hemoglobin From Baseline To Week 5 | 1.63 g/dL | Standard Deviation 1.535 |
Secondary
Mean Change In Hemoglobin Per Gram Of Iron Administered From Baseline To Week 5
Mean change in hemoglobin per g of iron administered from Baseline (Day 1) to Week 5 was calculated for each participant as: Hemoglobin Change = Hemoglobin (Week 5) - Hemoglobin (Baseline). Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information.
Time frame: Baseline (Day 1), Week 5
Population: ITT population: any randomized participant who had any exposure to study drug, based on randomized treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol | Mean Change In Hemoglobin Per Gram Of Iron Administered From Baseline To Week 5 | 1.35 g/dL | Standard Deviation 1.353 |
| Ferric Carboxymaltose (FCM) | Mean Change In Hemoglobin Per Gram Of Iron Administered From Baseline To Week 5 | 1.10 g/dL | Standard Deviation 1.05 |
Secondary
Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death
All IV iron formulations carry some risk of serious hypersensitivity reactions or anaphylaxis. Signs and symptoms potentially representing hypersensitivity were recorded and adjudicated by a blinded Clinical Events Committee (CEC). A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Day 1 (after first dosing) through Week 5
Population: The safety population included any randomized participant who received any amount of study drug. Treatment group was based on actual treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ferumoxytol | Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Moderate hypersensitivity reaction | 3 Participants |
| Ferumoxytol | Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Severe hypersensitivity reaction | 1 Participants |
| Ferumoxytol | Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Anaphylaxis | 0 Participants |
| Ferumoxytol | Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Serious cardiovascular event | 6 Participants |
| Ferumoxytol | Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Death | 4 Participants |
| Ferumoxytol | Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Any moderate to severe hypersensitivity rxn | 13 Participants |
| Ferric Carboxymaltose (FCM) | Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Death | 2 Participants |
| Ferric Carboxymaltose (FCM) | Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Moderate hypersensitivity reaction | 6 Participants |
| Ferric Carboxymaltose (FCM) | Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Serious cardiovascular event | 13 Participants |
| Ferric Carboxymaltose (FCM) | Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Severe hypersensitivity reaction | 0 Participants |
| Ferric Carboxymaltose (FCM) | Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Any moderate to severe hypersensitivity rxn | 20 Participants |
| Ferric Carboxymaltose (FCM) | Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death | Anaphylaxis | 0 Participants |