Anemia, Iron Deficiency, Kidney Disease
Conditions
Keywords
Iron deficiency anemia, Chronic kidney disease, Feraheme, Ferumoxytol, Iron sucrose, IDA, CKD, Venofer
Brief summary
The purpose of the study is to evaluate the safety and efficacy of intravenous (IV) ferumoxytol compared to IV iron sucrose for the treatment of iron deficiency anemia (IDA) in participants with chronic kidney disease (CKD).
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. An estimated glomerular filtration rate \<60 mL/minute or a diagnosis of CKD (such as nephropathy, nephritis) 3. Hemoglobin \<11.0 g/deciliter (dL) 4. Transferrin saturation \<30% 5. Hemodialysis participants on maintenance dialysis for at least 3 months prior to screening and currently receiving dialysis 3 times per week 6. Female participants 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 the study
Exclusion criteria
Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change In Hemoglobin From Baseline (Day 1) To Week 5 | Baseline (Day 1), Week 5 | The change in hemoglobin from Baseline (Day 1) to Week 5 was calculated for each participant as: Hemoglobin Change = Hemoglobin (Week 5) - Hemoglobin (Baseline) The least squares mean, with standard error, is reported as g/deciliter (dL). Baseline hemoglobin for each participant was the Day 1 hemoglobin value (prior to injection of the study drug). The screening hemoglobin value was used for any participants with missing Baseline (Day 1) hemoglobin. Analysis used last observed carried forward (LOCF) imputation methods for missing values for the ITT population. Sensitivity analyses were performed without imputation for missing data and with the Markov chain Monte Carlo method. |
| Percentage Of Participants With An Increase In Hemoglobin ≥1.0 g/dL From Day 1 (Baseline) To Week 5 | Baseline (Day 1) and up to Week 5 | The percentage of participants who achieved a ≥1.0 g/dL increase in hemoglobin at any time from Baseline (Day 1) up to Week 5 by treatment group is presented by study visit. Baseline hemoglobin for each participant was the Day 1 hemoglobin value (prior to injection of the study drug). |
Countries
Belgium, Canada, Germany, India, Poland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ferumoxytol Participants received an IV injection of ferumoxytol (510 mg, 17 mL) on Day 1 (Baseline). This was followed by a second injection of ferumoxytol (510 mg, 17 mL) 5±3 days later for a total cumulative dose of 1.02 g. | 80 |
| Iron Sucrose Participants received iron sucrose based on hemodialysis status. Participants on hemodialysis received either slow IV injection or IV drip infusion of 100 mg of iron sucrose on Day 1 (Baseline) and at the following 9 consecutive hemodialysis sessions for a total cumulative dose of 1.0 g.
Participants not on dialysis received either slow IV injection or IV drip infusion of 200 mg of iron sucrose on Day 1 (Baseline) and at 4 subsequent visits on nonconsecutive days over a 14-day period for a total cumulative dose of 1.0 g. | 82 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 |
| Overall Study | Other-Missed Week 5 Visit | 2 | 0 |
| Overall Study | Other-Protocol Violation | 1 | 1 |
| Overall Study | Other-Surgery | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Iron Sucrose | Total | Ferumoxytol |
|---|---|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 15.16 | 62.6 years STANDARD_DEVIATION 15.05 | 61.9 years STANDARD_DEVIATION 15 |
| Dialysis Status Hemodialysis | 36 Participants | 70 Participants | 34 Participants |
| Dialysis Status Nondialysis | 46 Participants | 92 Participants | 46 Participants |
| Sex: Female, Male Female | 39 Participants | 80 Participants | 41 Participants |
| Sex: Female, Male Male | 43 Participants | 82 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 80 | 50 / 82 |
| serious Total, serious adverse events | 7 / 80 | 6 / 82 |
Outcome results
Primary
Mean Change In Hemoglobin From Baseline (Day 1) To Week 5
The change in hemoglobin from Baseline (Day 1) to Week 5 was calculated for each participant as: Hemoglobin Change = Hemoglobin (Week 5) - Hemoglobin (Baseline) The least squares mean, with standard error, is reported as g/deciliter (dL). Baseline hemoglobin for each participant was the Day 1 hemoglobin value (prior to injection of the study drug). The screening hemoglobin value was used for any participants with missing Baseline (Day 1) hemoglobin. Analysis used last observed carried forward (LOCF) imputation methods for missing values for the ITT population. Sensitivity analyses were performed without imputation for missing data and with the Markov chain Monte Carlo method.
Time frame: Baseline (Day 1), Week 5
Population: ITT Population: Any randomized participant who had any exposure to study drug (IV ferumoxytol or IV iron sucrose).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ferumoxytol | Mean Change In Hemoglobin From Baseline (Day 1) To Week 5 | Without Imputation (Sensitivity Analysis) | 0.89 g/dL | Standard Error 0.15 |
| Ferumoxytol | Mean Change In Hemoglobin From Baseline (Day 1) To Week 5 | With LOCF Imputation | 0.84 g/dL | Standard Error 0.14 |
| Iron Sucrose | Mean Change In Hemoglobin From Baseline (Day 1) To Week 5 | With LOCF Imputation | 0.74 g/dL | Standard Error 0.14 |
| Iron Sucrose | Mean Change In Hemoglobin From Baseline (Day 1) To Week 5 | Without Imputation (Sensitivity Analysis) | 0.80 g/dL | Standard Error 0.15 |
Comparison: With LOCF Imputation: The p-value and two-sided 95% confidence interval (CI) for the treatment difference in mean change in hemoglobin from Baseline (Day 1) to Week 5 were generated based on an analysis of variance (ANOVA) model adjusted for baseline hemoglobin level and hemodialysis status.p-value: 0.51595% CI: [-0.21, 0.41]ANOVA
Comparison: Without Imputation (Sensitivity Analysis): The p-value and two-sided 95% CI for the treatment difference in mean change in hemoglobin from Baseline (Day 1) to Week 5 were generated based on an ANOVA model adjusted for baseline hemoglobin level and hemodialysis status.p-value: 0.58795% CI: [-0.23, 0.41]ANOVA
Primary
Percentage Of Participants With An Increase In Hemoglobin ≥1.0 g/dL From Day 1 (Baseline) To Week 5
The percentage of participants who achieved a ≥1.0 g/dL increase in hemoglobin at any time from Baseline (Day 1) up to Week 5 by treatment group is presented by study visit. Baseline hemoglobin for each participant was the Day 1 hemoglobin value (prior to injection of the study drug).
Time frame: Baseline (Day 1) and up to Week 5
Population: ITT Population: Any randomized participant who had any exposure to study drug (IV ferumoxytol or IV iron sucrose).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ferumoxytol | Percentage Of Participants With An Increase In Hemoglobin ≥1.0 g/dL From Day 1 (Baseline) To Week 5 | Week 3 | 32 Participants |
| Ferumoxytol | Percentage Of Participants With An Increase In Hemoglobin ≥1.0 g/dL From Day 1 (Baseline) To Week 5 | Week 2 | 20 Participants |
| Ferumoxytol | Percentage Of Participants With An Increase In Hemoglobin ≥1.0 g/dL From Day 1 (Baseline) To Week 5 | Week 4 | 37 Participants |
| Ferumoxytol | Percentage Of Participants With An Increase In Hemoglobin ≥1.0 g/dL From Day 1 (Baseline) To Week 5 | Week 5 | 40 Participants |
| Iron Sucrose | Percentage Of Participants With An Increase In Hemoglobin ≥1.0 g/dL From Day 1 (Baseline) To Week 5 | Week 5 | 34 Participants |
| Iron Sucrose | Percentage Of Participants With An Increase In Hemoglobin ≥1.0 g/dL From Day 1 (Baseline) To Week 5 | Week 3 | 20 Participants |
| Iron Sucrose | Percentage Of Participants With An Increase In Hemoglobin ≥1.0 g/dL From Day 1 (Baseline) To Week 5 | Week 4 | 31 Participants |
| Iron Sucrose | Percentage Of Participants With An Increase In Hemoglobin ≥1.0 g/dL From Day 1 (Baseline) To Week 5 | Week 2 | 11 Participants |