Iron Deficiency Anemia
Conditions
Keywords
Iron deficiency anemia, Feraheme, ferumoxytol, CKD, pediatric, dialysis-dependent, nondialysis-dependent
Brief summary
Study evaluating the efficacy and safety of intravenous (IV) ferumoxytol compared with oral iron for the treatment of pediatric participants with chronic kidney disease (CKD).
Detailed description
Study AMAG-FER-CKD-251 was a study evaluating the efficacy and safety of IV ferumoxytol in pediatric participants with dialysis-dependent CKD. Study AMAG-FER-CKD-252 (NCT01155388) was a study evaluating the efficacy and safety of IV ferumoxytol in pediatric participants with nondialysis-dependent CKD. Due to significant challenges with enrollment for both studies, Study AMAG-FER-CKD-252 was combined with Study AMAG-FER-CKD-251 and enrollment continued under Study AMAG-FER-CKD-251. The enrollment number (n=14) includes the number of participants for both AMAG-FER-CKD-251 and AMAG-FER-CKD-252 studies, combined. Participants were enrolled by age cohorts in a stepwise manner following a safety review by the Data Safety Monitoring Board of 1 age cohort prior to enrollment of a subsequent age cohort, with progression from oldest to youngest: Randomization was stratified by the following age cohorts: 12 to \<18 years, 6 to \<12 years, 2 to \<6 years, and 6 months to \<2 years.
Interventions
DRUGFerumoxytol
Experimental: Ferumoxytol
DRUGOral Iron
Active Comparator: Oral iron
Sponsors
AMAG Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria for the combined AMAG-FER-CKD-251 and AMAG-FER-CDK-252 studies include: 1. Males or females 6 months to \<18 years of age 2. CKD non-dialysis participants or dialysis-dependent participants who were on peritoneal dialysis or stable hemodialysis prior to Screening 3. Had iron deficiency anemia defined as: a) hemoglobin level ≤12.0 grams/deciliter (g/dL) and b) with either transferrin saturation level ≤40% or ferritin level \<100 nanograms/milliliter (ng/mL) 4. Female participants of childbearing potential who were sexually active must have been on an effective method of birth control for at least 1 month prior to Screening and agreed to remain on birth control until completion of participation in the study Key
Exclusion criteria
for the combined AMAG-FER-CKD-251 and AMAG-FER-CDK-252 studies include: 1. History of allergy to either oral or IV iron 2. Hemoglobin level ≤7.0 g/dL 3. Serum ferritin level \>600 ng/mL 4. Female participants who were pregnant or intended to become pregnant, or were breastfeeding, were within 3 months postpartum, or had a positive serum pregnancy test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change In Hemoglobin From Baseline To Week 5 | Baseline, Week 5 | Mean changes in hemoglobin from Baseline to Week 5 were to be presented. Despite efforts to complete the studies as designed, several factors contributed to significant challenges in enrollment and led the Sponsor to discontinue the combined AMAG-FER-CKD-251 and AMAG-FER-CKD-252 studies. Blood samples were collected, but not run through an analysis to obtain outcome measure data. As such, the data set for this primary outcome measure cannot be summarized nor can the statistical analysis, as described in the protocol, be provided in a way that will provide any significant data based upon the limited study datasets. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Area Under The Curve Of Ferumoxytol | Baseline; 10, 30, 120, and 360 minutes postdose; 24, 48, and 72 hours postdose | Ferumoxytol concentrations were to be determined using a drug-specific nuclear magnetic resonance assay. Blood samples were to be collected at specified times predose and postdose at the time of the first dose from 6 participants in each age-dose group. Sampling for participants \<6 years of age will be minimized to the fewest number of time points required for population PK analysis based on preliminary PK data from the first 2 age cohorts. Blood samples were collected, but not run through an analysis to obtain outcome measure data. As such, the data set for this secondary outcome measure cannot be summarized in a way that will provide any significant data based upon the limited study datasets. |
Countries
United States
Participant flow
Pre-assignment details
Due to significant challenges with enrollment for both studies, Study AMAG-FER-CKD-252 (NCT01155388) was combined with Study AMAG-FER-CKD-251 and enrollment continued under Study AMAG-FER-CKD-251. The results for the combined studies are included in this record.
Participants by arm
| Arm | Count |
|---|---|
| Ferumoxytol Participants received 1 of the following 2 ferumoxytol dose regimens:
* Four IV injections of ferumoxytol 3.5 mg Fe/kg (maximum of 255 mg/dose) administered on nonconsecutive days within a 14-day period as follows: Day 1 (dose 1), Days 3\* through 10 (dose 2), Days 5 through 12 (dose 3), and Days 7 through 14 (dose 4). \*Participants participating in PK sampling received the second dose on Day 4 after the 72-hour PK sample was collected.
* Two IV injections of ferumoxytol 7.0 mg Fe/kg (maximum of 510 mg/dose), the first administered on Day 1 and the second on Days 3 through 9. | 8 |
| Oral Iron Participants received oral iron 2.5 mg Fe/kg twice daily (maximum of 100 mg/dose) on Days 1 through 35. | 6 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Ferumoxytol | Oral Iron | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 6 Participants | 14 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 15.2 years STANDARD_DEVIATION 1.65 | 13.8 years STANDARD_DEVIATION 4.52 | 14.6 years STANDARD_DEVIATION 2.93 |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 |
| other Total, other adverse events | 6 / 8 | 5 / 6 |
| serious Total, serious adverse events | 1 / 8 | 1 / 6 |
Outcome results
Primary
Mean Change In Hemoglobin From Baseline To Week 5
Mean changes in hemoglobin from Baseline to Week 5 were to be presented. Despite efforts to complete the studies as designed, several factors contributed to significant challenges in enrollment and led the Sponsor to discontinue the combined AMAG-FER-CKD-251 and AMAG-FER-CKD-252 studies. Blood samples were collected, but not run through an analysis to obtain outcome measure data. As such, the data set for this primary outcome measure cannot be summarized nor can the statistical analysis, as described in the protocol, be provided in a way that will provide any significant data based upon the limited study datasets.
Time frame: Baseline, Week 5
Population: Intent-to-Treat Population included all randomized participants who had received at least 1 dose of study drug. Sample data were collected, but not run through any analysis to obtain outcome measure data. As such, summary of the data set is not possible.
Secondary
Pharmacokinetics: Area Under The Curve Of Ferumoxytol
Ferumoxytol concentrations were to be determined using a drug-specific nuclear magnetic resonance assay. Blood samples were to be collected at specified times predose and postdose at the time of the first dose from 6 participants in each age-dose group. Sampling for participants \<6 years of age will be minimized to the fewest number of time points required for population PK analysis based on preliminary PK data from the first 2 age cohorts. Blood samples were collected, but not run through an analysis to obtain outcome measure data. As such, the data set for this secondary outcome measure cannot be summarized in a way that will provide any significant data based upon the limited study datasets.
Time frame: Baseline; 10, 30, 120, and 360 minutes postdose; 24, 48, and 72 hours postdose
Population: The PK population included all randomized participants who received at least 1 dose of study drug and consented to PK sampling. Sample data were collected, but not run through any analysis to obtain outcome measure data. As such, summary of the data set is not possible.