Eculizumab Pharmacokinetics/Pharmacodynamics Study in Pediatric/Adolescent Paroxysmal Nocturnal Hemoglobinuria (PNH)

An Open-Label Multi-Center Study of Eculizumab in Children and Adolescents With a Diagnosis of Paroxysmal Nocturnal Hemoglobinuria

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.

Inclusion Criteria:

• Participants between 2 and 17 years of age;
• Diagnosed with PNH;
• Participants with ≥ 5% glycosylphosphatidylinositol-deficient red blood cells or granulocytes as confirmed by flow cytometry;
• Participants must have shown evidence of hemolytic anemia as documented by lactate dehydrogenase greater than the upper limit of normal or at least 1 transfusion in the past 2 years for anemia or anemia related symptoms;
• Written informed consent from a parent/guardian;
• Negative pregnancy test for females of child bearing potential at screening;
• Sexually active females must have documented a reliable and medically approved method of contraception;
• Participant must have been vaccinated against N. men, S. pneumo, and H. influ at least 14 days prior to study drug initiation or received antibiotics for 14 days after the vaccinations.

Exclusion Criteria:

• Prior eculizumab treatment;
• Presence or suspicion of active bacterial infection at baseline;
• Participation in another concurrent clinical study within at least 30 days prior to screening;
• History of meningococcal/pneumococcal/gonococcal disease;
• Pregnant, breast feeding, or intending to conceive during the study including the safety follow-up visits;
• Any other condition that could increase the participant's risk or confound the outcome of the study.