A Trial of Ferumoxytol for the Treatment of Iron Deficiency Anemia in Pediatric Participants With Chronic Kidney Disease
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ferumoxytol Participants will receive 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. |
Drug: Ferumoxytol
Experimental: Ferumoxytol
|
| Active Comparator: Oral Iron Participants will receive oral iron 2.5 mg Fe/kg twice daily (maximum of 100 mg/dose) on Days 1 through 35. |
Drug: Oral Iron
Active Comparator: Oral iron
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Key Inclusion Criteria for the combined AMAG-FER-CKD-251 and AMAG-FER-CDK-252 studies include:
-
Males or females 6 months to <18 years of age
-
CKD non-dialysis participants or dialysis-dependent participants who were on peritoneal dialysis or stable hemodialysis prior to Screening
-
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)
-
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:
-
History of allergy to either oral or IV iron
-
Hemoglobin level ≤7.0 g/dL
-
Serum ferritin level >600 ng/mL
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | AMAG Pharmaceuticals, Inc. | Waltham | Massachusetts | United States | 02451 |
Sponsors and Collaborators
- AMAG Pharmaceuticals, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AMAG-FER-CKD-251
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Ferumoxytol | Oral Iron |
|---|---|---|
| Arm/Group Description | Participants received 1 of the following 2 ferumoxytol dose regimens: Four intravenous (IV) injections of ferumoxytol 3.5 milligrams (mg) iron (Fe)/kilogram (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 pharmacokinetic (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. | Participants received oral iron 2.5 mg Fe/kg twice daily (maximum of 100 mg/dose) on Days 1 through 35. |
| Period Title: Overall Study | ||
| STARTED | 8 | 6 |
| Received at Least 1 Dose of Study Drug | 8 | 6 |
| COMPLETED | 7 | 6 |
| NOT COMPLETED | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Ferumoxytol | Oral Iron | Total |
|---|---|---|---|
| Arm/Group Description | 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. | Participants received oral iron 2.5 mg Fe/kg twice daily (maximum of 100 mg/dose) on Days 1 through 35. | Total of all reporting groups |
| Overall Participants | 8 | 6 | 14 |
| Age (Count of Participants) | |||
| <=18 years |
8
100%
|
6
100%
|
14
100%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
15.2
(1.65)
|
13.8
(4.52)
|
14.6
(2.93)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
5
62.5%
|
1
16.7%
|
6
42.9%
|
| Male |
3
37.5%
|
5
83.3%
|
8
57.1%
|
Outcome Measures
| Title | Mean Change In Hemoglobin From Baseline To Week 5 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Ferumoxytol | Oral Iron |
|---|---|---|
| Arm/Group Description | 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. | Participants received oral iron 2.5 mg Fe/kg twice daily (maximum of 100 mg/dose) on Days 1 through 35. |
| Measure Participants | 0 | 0 |
| Title | Pharmacokinetics: Area Under The Curve Of Ferumoxytol |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Ferumoxytol | Oral Iron |
|---|---|---|
| Arm/Group Description | 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. | Participants received oral iron 2.5 mg Fe/kg twice daily (maximum of 100 mg/dose) on Days 1 through 35. |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | Randomization up to 7 weeks (Follow-up) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | 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 adverse events for the combined studies are included in this record. | |||
| Arm/Group Title | Ferumoxytol | Oral Iron | ||
| Arm/Group Description | 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. | Participants received oral iron 2.5 mg Fe/kg twice daily (maximum of 100 mg/dose) on Days 1 through 35. | ||
All Cause Mortality |
||||
| Ferumoxytol | Oral Iron | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | 0/6 (0%) | ||
Serious Adverse Events |
||||
| Ferumoxytol | Oral Iron | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/8 (12.5%) | 1/6 (16.7%) | ||
| Infections and infestations | ||||
| Acute Gastroenteritis | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| Metabolism and nutrition disorders | ||||
| Hyperkalemia | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Ferumoxytol | Oral Iron | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/8 (75%) | 5/6 (83.3%) | ||
| Blood and lymphatic system disorders | ||||
| Leukopenia | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| Cardiac disorders | ||||
| Ventricular flutter | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Food poisoning | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| General disorders | ||||
| Fatigue | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Pyrexia | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| Immune system disorders | ||||
| Hypersensitivity | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Infections and infestations | ||||
| Chronic sinusitis | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Nasopharyngitis | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| Pneumonia | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Pharyngitis | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Urinary tract infection | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| Viral pharyngitis | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Procedural hypotension | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Procedural nausea | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Skin injury | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| Investigations | ||||
| Residual urine volume decreased | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Fluid retention | 1/8 (12.5%) | 1 | 1/6 (16.7%) | 1 |
| Hypermagnesaemia | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal pain | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Psychiatric disorders | ||||
| Sleep disorder | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Oropharyngeal pain | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Vascular disorders | ||||
| Hypertension | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If there is no multi-site publication within 18 months after the Study has been completed or terminated at all Study sites, and all data have been received by Sponsor, the Site, and SMO shall have the right to publish its results from the Study for non-commercial purposes, if submitted to Sponsor for review 60 days prior to submission of publication. Publication must remove all confidential information and may be delayed by up to 120 days to allow Sponsor to protect its interests.
Results Point of Contact
| Name/Title | Medical Information |
|---|---|
| Organization | AMAG Pharmaceuticals, Inc. |
| Phone | +1-877-411-2510 |
| amag@druginfo.com |
- AMAG-FER-CKD-251