The primary objective of this study was to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) parameter estimates of eculizumab to confirm the dose regimens for pediatric and adolescent participants with PNH.
This was an open-label, multi-center study of eculizumab administered to approximately 6 to 8 pediatric and adolescent participants aged 2 to 17 years with PNH. There were 3 periods in this study (screening, treatment, and post-treatment) with the treatment period having 2 dosing phases (induction and maintenance). If all screening criteria were met, the participant was eligible to enter the treatment period of the study after receiving Neisseria meningitidis (N. men), Streptococcus pneumoniae (S. pneumo), and Haemophilus influenzae (H. influ) vaccinations at least 14 days prior to first dose of study drug, or was vaccinated and received treatment with appropriate antibiotics until 14 days after the vaccinations. Participants received eculizumab intravenously (IV) based on their weight. Eculizumab was administered via an IV infusion at a rate of 5 to 10 milliliters (mL) per kilogram (kg) per hour (hr) (mL/kg/hr) for at least 25 minutes. The planned duration of treatment was 12 weeks with a 4-week induction phase and an 8-week maintenance phase. At the Investigator's and parents/legal guardian's discretion, participants who completed this study with eculizumab could continue treatment with commercially available eculizumab (Soliris®) and were followed in the Soliris® PNH Registry. Participants who stopped study participation before study completion or who did not continue with Soliris® treatment at the completion of the study were followed for 8 weeks and monitored for signs and symptoms of serious hemolysis.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
5 mg/mL solution in 5% Dextrose
Unnamed facility
Orange, California, United States
Unnamed facility
Pensacola, Florida, United States
Unnamed facility
Memphis, Tennessee, United States
Peak And Trough Concentrations Of Eculizumab In Serum At Week 12
Serum concentrations of eculizumab were measured by using a validated enzyme-linked immunosorbent assay (ELISA) method developed at Alexion Pharmaceuticals Bioanalytical Laboratory. The range of the analytical assay was 10 to 600 microgram per milliliter (μg/mL). Peak concentrations were not measured at the early termination (ET) visit.
Time frame: Pre-infusion and 1 hour post-infusion at End of Treatment (EOT) (Day 84 [Week 12]) or ET
Number Of Participants With Treatment-emergent Adverse Events (TEAEs)
A TEAE was defined as any adverse event (AE) not present prior to exposure to eculizumab or any event already present that worsened in either intensity or frequency following exposure to eculizumab. A serious TEAE was defined as any event that resulted in death, was immediately life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. Related TEAEs were considered by investigators to be definitely, probably, or possibly related to administration of the study drug. Relationship is ordered as follows: unrelated, possibly related, probably related, or definitely related. TEAEs and TEAE severity were classified in accordance with the Medical Dictionary for Regulatory Activities (MedDRA) 13.0 dictionary. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time frame: First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Area Under The Curve (AUC) Of The Change From Baseline To Week 12 In Levels Of Lactate Dehydrogenase (LDH)
The AUC of LDH was calculated by using the change of LDH from baseline values for each participant up to Week 12. For those participants with missing LDH values, the last observation carried forward method (LOCF) was used to impute missing values. Individual AUC values of LDH were summarized and tabulated.
Time frame: Baseline, EOT (Day 84 [Week 12]) or ET
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Concentration Of Plasma-free Hemoglobin At Baseline And Week 12
Plasma-free hemoglobin was determined for each participant by using standard laboratory assays. The values of plasma-free hemoglobin were summarized by visit.
Time frame: Baseline, EOT (Day 84 [Week 12]) or ET
Change From Baseline In LDH Levels
Levels of LDH were determined by using standard laboratory assays. LDH values and the change of LDH from baseline were summarized by visit.
Time frame: Baseline, Weeks 1 to 12 or ET