Iron Deficiency Anemia (IDA)
Conditions
Brief summary
This is a Phase II, open-label, non-randomized, multi-center, single arm study to characterize the pharmacokinetic and pharmacodynamics (PK/PD) profile of Ferric Carboxymaltose dosing in pediatric subjects with IDA after receiving either a 7.5 mg/kg or 15 mg/kg dose of Ferric Carboxymaltose.
Detailed description
This is a Phase II, open-label, non-randomized, multi-center, single arm study to characterize the pharmacokinetic and pharmacodynamics (PK/PD) profile of Ferric Carboxymaltose dosing in pediatric subjects with IDA after receiving either a 7.5 mg/kg or 15 mg/kg dose of Ferric Carboxymaltose.
Interventions
Sponsors
American Regent, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Eligible subjects were enrolled sequentially in Cohort 1 (FCM at 7.5 mg/kg with a maximum single dose of 750 mg) and Cohort 2 (FCM at 15 mg/kg with a maximum single dose of 750 mg). Enrollment in Cohort 2 was initiated only after all subjects in Cohort 1 completed 4 weeks of therapy and a Data and Safety Monitoring Board (DSMB) approved continuation.
Eligibility
Sex/Gender
ALL
Age
1 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects 1 to 17 years of age with assent to participation and his/her parent or guardian is willing and able to sign the informed consent approved by the Independent Review Board / Ethics Committee. * Screening TSAT \< 20% * Screening Hemoglobin \< 11 g/dL * For subjects who are receiving an erythropoietin stimulating agent (ESA): stable ESA therapy (+/- 20% of current dose) for \> 8 weeks prior to the qualifying screening visit and no ESA dosing or product changes anticipated for the length of the trial
Exclusion criteria
* Known hypersensitivity reaction to any component of Ferric Carboxymaltose. * Subject previously randomized and treated in this study or any other clinical study of Ferric Carboxymaltose (FCM or VIT-45). * Body mass index (BMI) ≤ 5th percentile for age (see APPENDIX 2) * Male or Female subject 1 year of age weighing \< 12kg. * History of acquired iron overload, hemochromatosis or other iron accumulation disorders. * Chronic kidney disease subjects on hemodialysis. * Screening Ferritin level \> 300ng/mL * Subjects with significant severe diseases of the liver, hemopoietic system, cardiovascular system, psychiatric disorder or other conditions which on the opinion of the investigator may place a subject at added risk. * Any active infection. * Known positive hepatitis B antigen (HBsAg) or hepatitis C viral antibody (HCV) with evidence of active hepatitis. * Known positive HIV-1/HIV-2 antibodies (anti-HIV). * Anemia due to reasons other than iron deficiency (i.e. hemoglobinopathy). Subjects treated with vitamin B12 or folic acid deficiency are permitted. * Intravenous iron and /or blood transfusion in the 4 weeks prior to screening. * Immunosuppressive therapy that may lead to anemia (i.e. cyclophosphamide, azathioprine, mycophenolate mofetil). Note steroid therapy is permitted. * Administration and / or use of an investigational product (drug or device) within 30 days of screening. * Alcohol or drug abuse within the past six months. * Female subjects who are pregnant or lactating, or sexually active female who are of childbearing potential not willing to use an acceptable form of contraceptive precautions during the study. * Subject is unable to comply with study assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) | prior to dosing and 1, 2, 6, 12, 48 and 72 hours post dosing | Maximum observed serum concentration; obtained directly from the serum concentration-time profile. |
Countries
Poland, Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ferric Carboxymaltose (FCM) FCM at 7.5 mg/kg or 15 mg/kg to a maximum single dose of 750 mg iron, whichever is smaller
Ferric Carboxymaltose (FCM) | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | Ferric Carboxymaltose (FCM) |
|---|---|
| Age, Continuous Cohort 1 (FCM at 7.5 mg/kg to a maximum of 750mg) | 9.1 years STANDARD_DEVIATION 6.13 |
| Age, Continuous Cohort 2 (FCM at 15 mg/kg to a maximum of 750mg) | 10.3 years STANDARD_DEVIATION 5.77 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 35 Participants |
| Region of Enrollment Poland | 30 participants |
| Region of Enrollment Russia | 5 participants |
| Sex: Female, Male Cohort 1 (FCM at 7.5 mg/kg to a maximum of 750mg) Female | 10 Participants |
| Sex: Female, Male Cohort 1 (FCM at 7.5 mg/kg to a maximum of 750mg) Male | 6 Participants |
| Sex: Female, Male Cohort 2 (FCM at 15 mg/kg to a maximum of 750mg Female | 9 Participants |
| Sex: Female, Male Cohort 2 (FCM at 15 mg/kg to a maximum of 750mg Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 19 |
| other Total, other adverse events | 9 / 16 | 12 / 19 |
| serious Total, serious adverse events | 2 / 16 | 0 / 19 |
Outcome results
Primary
Maximum Serum Concentration (Cmax)
Maximum observed serum concentration; obtained directly from the serum concentration-time profile.
Time frame: prior to dosing and 1, 2, 6, 12, 48 and 72 hours post dosing
Population: In Cohort 1, pharmacokinetic parameter values are excluded for one subject due to anomalous and consistently high concentrations, and for one subject due to missing concentration data at 1 and 2 hours post-dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Ferric Carboxymaltose (FCM) 7.5 mg | Maximum Serum Concentration (Cmax) | 157 µg/mL | Standard Deviation 33.8 |
| Cohort 2: Ferric Carboxymaltose (FCM) 15 mg/kg | Maximum Serum Concentration (Cmax) | 310 µg/mL | Standard Deviation 13.9 |