Chronic Kidney Disease(CKD), Iron Deficiency Anemia Treatment
Conditions
Keywords
Iron deficiency anemia (IDA), chronic kidney disease (CKD), hemodialysis, magnetic resonance imaging (MRI), ferumoxytol, Feraheme
Brief summary
The objectives of this study are to compare the efficacy and safety of repeat doses of intravenous (IV) ferumoxytol with IV iron sucrose for the treatment of IDA in subjects with hemodialysis-dependent CKD.
Detailed description
This was a Phase IV, randomized, open-label, active-controlled, multicenter clinical trial designed to evaluate the safety, efficacy, and frequency of use of ferumoxytol compared to iron sucrose for the episodic treatment of IDA in hemodialysis subjects with CKD over a 1-year period. As part of this Main Study, an Oxidative Stress Substudy and an MRI Substudy were conducted. The Oxidative Stress Substudy, to be run concurrently with the initial TP of the Main Study, was to examine the varying degrees to which iron sucrose and ferumoxytol may or may not induce oxidative stress in vitro in subjects undergoing hemodialysis. The MRI Substudy, to be run concurrently with the Main Study and continue for an additional 11 months, was to assess the potential for deposition of iron in cardiac, hepatic, and pancreatic tissues and changes in laboratory parameters over a 2-year period.
Interventions
DRUGFerumoxytol
IV Ferumoxytol
DRUGIron Sucrose
IV Iron Sucrose
Sponsors
AMAG Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria include: 1. Males and females ≥18 years of age 2. Diagnosis of CKD 3. Subjects on dialysis must have been on dialysis for at least 3 months prior to screening 4. Female subjects of childbearing potential who are sexually active must be on an effective method of birth control for at least 1 month prior to screening and agree to remain on birth control until completion of participation in the study Key
Exclusion criteria
include: 1. History of allergy to either oral or IV iron 2. Female subjects who are pregnant or intend to become pregnant, breastfeeding, within 3 months postpartum, or have a positive serum or urine pregnancy test 3. Parenteral iron therapy within 30 days prior to screening or red blood cell (RBC)/whole blood transfusion within 14 days prior to screening or planned during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin Changes | Up to 6 treatment periods (5 weeks per treatment period) | Changes in the mean hemoglobin between Baseline and Week 5 for ferumoxytol and iron sucrose in each treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Transferrin Saturation (TSAT) | Up to 6 treatment periods (5 weeks per treatment period) | Mean change in TSAT from TP Baseline to Week 5 for each TP |
| Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | Up to 6 treatment periods (5 weeks per treatment period) | The proportion of subjects by group achieving a ≥1.0 g/dL increase in hemoglobin at any point during each 5-week treatment period. |
Countries
Canada, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 296 hemodialysis patients with IDA who met the entry criteria were enrolled and randomized (ferumoxytol: n=197; iron sucrose: n=99). One subject in the ferumoxytol group and 2 subjects in the iron sucrose group withdrew prior to receiving study drug, resulting in 293 total participants for analysis.
Participants by arm
| Arm | Count |
|---|---|
| Ferumoxytol 30 mg Fe/mL for IV injection | 196 |
| Iron Sucrose 20 mg Fe/mL for IV injection | 97 |
| Total | 293 |
Baseline characteristics
| Characteristic | Total | Ferumoxytol | Iron Sucrose |
|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 13.96 | 59.3 years STANDARD_DEVIATION 14.13 | 57.6 years STANDARD_DEVIATION 13.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 108 Participants | 68 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 185 Participants | 128 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Mean Hemoglobin | 10.4 g/dL STANDARD_DEVIATION 0.76 | 10.4 g/dL STANDARD_DEVIATION 0.74 | 10.4 g/dL STANDARD_DEVIATION 0.81 |
| Race (NIH/OMB) American Indian or Alaska Native | 14 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 15 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 88 Participants | 62 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 10 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 148 Participants | 101 Participants | 47 Participants |
| Region of Enrollment Canada | 7 participants | 5 participants | 2 participants |
| Region of Enrollment United Kingdom | 11 participants | 6 participants | 5 participants |
| Region of Enrollment United States | 275 participants | 185 participants | 90 participants |
| Sex: Female, Male Female | 122 Participants | 82 Participants | 40 Participants |
| Sex: Female, Male Male | 171 Participants | 114 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 196 | 6 / 97 |
| other Total, other adverse events | 158 / 196 | 81 / 97 |
| serious Total, serious adverse events | 93 / 196 | 49 / 97 |
Outcome results
Primary
Hemoglobin Changes
Changes in the mean hemoglobin between Baseline and Week 5 for ferumoxytol and iron sucrose in each treatment period.
Time frame: Up to 6 treatment periods (5 weeks per treatment period)
Population: Mean Change in Hemoglobin at Week 5 - ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferumoxytol | Hemoglobin Changes | TP6 | 0.5 g/dL | Standard Deviation 1.21 |
| Ferumoxytol | Hemoglobin Changes | TP1 | 0.5 g/dL | Standard Deviation 0.97 |
| Ferumoxytol | Hemoglobin Changes | TP2 | 0.6 g/dL | Standard Deviation 0.96 |
| Ferumoxytol | Hemoglobin Changes | TP3 | 0.6 g/dL | Standard Deviation 1.1 |
| Ferumoxytol | Hemoglobin Changes | TP4 | 0.5 g/dL | Standard Deviation 1.12 |
| Ferumoxytol | Hemoglobin Changes | TP5 | 0.4 g/dL | Standard Deviation 1.14 |
| Iron Sucrose | Hemoglobin Changes | TP4 | 0.6 g/dL | Standard Deviation 1.11 |
| Iron Sucrose | Hemoglobin Changes | TP6 | -0.3 g/dL | Standard Deviation 1 |
| Iron Sucrose | Hemoglobin Changes | TP3 | 0.4 g/dL | Standard Deviation 0.87 |
| Iron Sucrose | Hemoglobin Changes | TP1 | 0.4 g/dL | Standard Deviation 0.97 |
| Iron Sucrose | Hemoglobin Changes | TP5 | 0.3 g/dL | Standard Deviation 0.96 |
| Iron Sucrose | Hemoglobin Changes | TP2 | 0.3 g/dL | Standard Deviation 1.03 |
p-value: <0.05ANCOVA
Secondary
Changes in Transferrin Saturation (TSAT)
Mean change in TSAT from TP Baseline to Week 5 for each TP
Time frame: Up to 6 treatment periods (5 weeks per treatment period)
Population: Mean Change in TSAT at Week 5 - ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferumoxytol | Changes in Transferrin Saturation (TSAT) | TP2 | 8.2 Percent | Standard Deviation 12.95 |
| Ferumoxytol | Changes in Transferrin Saturation (TSAT) | TP4 | 9.8 Percent | Standard Deviation 14.76 |
| Ferumoxytol | Changes in Transferrin Saturation (TSAT) | TP1 | 6.6 Percent | Standard Deviation 9.2 |
| Ferumoxytol | Changes in Transferrin Saturation (TSAT) | TP3 | 8.5 Percent | Standard Deviation 10.56 |
| Ferumoxytol | Changes in Transferrin Saturation (TSAT) | TP6 | 7.1 Percent | Standard Deviation 16.62 |
| Ferumoxytol | Changes in Transferrin Saturation (TSAT) | TP5 | 6.3 Percent | Standard Deviation 9.77 |
| Iron Sucrose | Changes in Transferrin Saturation (TSAT) | TP6 | 5.1 Percent | Standard Deviation 12.84 |
| Iron Sucrose | Changes in Transferrin Saturation (TSAT) | TP1 | 9.5 Percent | Standard Deviation 11.97 |
| Iron Sucrose | Changes in Transferrin Saturation (TSAT) | TP2 | 11.3 Percent | Standard Deviation 14.68 |
| Iron Sucrose | Changes in Transferrin Saturation (TSAT) | TP3 | 9.1 Percent | Standard Deviation 11.13 |
| Iron Sucrose | Changes in Transferrin Saturation (TSAT) | TP4 | 10.0 Percent | Standard Deviation 14.76 |
| Iron Sucrose | Changes in Transferrin Saturation (TSAT) | TP5 | 14.4 Percent | Standard Deviation 17.05 |
Secondary
Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP
The proportion of subjects by group achieving a ≥1.0 g/dL increase in hemoglobin at any point during each 5-week treatment period.
Time frame: Up to 6 treatment periods (5 weeks per treatment period)
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ferumoxytol | Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | TP1 | 55 participants |
| Ferumoxytol | Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | TP2 | 55 participants |
| Ferumoxytol | Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | TP3 | 42 participants |
| Ferumoxytol | Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | TP4 | 20 participants |
| Ferumoxytol | Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | TP5 | 13 participants |
| Ferumoxytol | Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | TP6 | 5 participants |
| Iron Sucrose | Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | TP5 | 3 participants |
| Iron Sucrose | Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | TP1 | 23 participants |
| Iron Sucrose | Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | TP4 | 10 participants |
| Iron Sucrose | Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | TP2 | 13 participants |
| Iron Sucrose | Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | TP6 | 1 participants |
| Iron Sucrose | Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP | TP3 | 19 participants |