O3
ECULIZUMAB TREATMENT OF PAEDIATRIC PATIENTS WITH ATYPICAL
HAEMOLYTIC URAEMIC SYNDROME: FIRST PROSPECTIVE CLINICAL TRIAL
Rees L,1 Greenbaum LA,2 Fila M,3 Tsimaratos M,4 Ardissino G,5 Al-Akash SI,6 Evans J,7
Henning P,8 Lieberman KV,9 Maringhini S,10 Pape L,11 van de Kar N,12 Vande Walle J,13
Ogawa M,14 Bedrosian CL,14 Licht C15
1
Great Ormond Street Hospital for Children, London, UK; 2Emory University, Atlanta,
USA; 3Hôpital Robert-Debré, Paris, France; 4Hôpital de la Timone, Marseille, France;
5
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy; 6Driscoll
Children’s Hospital, Corpus Christi, USA; 7Nottingham University Hospitals, Nottingham,
UK; 8Women’s and Children’s Hospital, North Adelaide, Australia; 9Hackensack
University Medical Center, Hackensack, USA; 10G. Di Cristina Children’s Hospital,
Palermo, Italy; 11Hannover Medical School, Hannover, Germany; 12Radboud University
Medical Centre, Nijmegen, The Netherlands; 13University Hospital Ghent, Ghent,
Belgium; 14Alexion Pharmaceuticals, Cheshire, USA; 15The Hospital for Sick Children,
Toronto, Canada
INTRODUCTION: Atypical haemolytic uraemic syndrome (aHUS) is a rare, genetic, lifethreatening disease in which uncontrolled complement activation leads to systemic thrombotic
microangiopathy (TMA) and severe end-organ damage. Eculizumab (Ecu) is a terminal
complement inhibitor approved for the treatment of aHUS. Retrospective data and case reports
have previously shown Ecu to be safe and effective for paediatric patients (pts) with aHUS. We
now report results from the first prospective clinical trial in children.
METHODS: Children with aHUS were recruited into an open-label, 26-week, single-arm,
phase 2 study, with Ecu dosing determined by weight as per approved dosing. Inclusion criteria
included platelet count <lower limit of normal at screening , lactate dehydrogenase (LDH)
≥1.5 upper limit of normal (ULN) at the start of TMA and serum creatinine ≥97th percentile
for age at screening. Pts with STEC-HUS (Shiga toxin and E. coli) and severe ADAMTS13
deficiency (activity <5%) were excluded. Assessments included complete TMA response
(primary endpoint: platelet and LDH normalisation [>150  109/L and < ULN, respectively],
and ≥25% decrease in serum creatinine from baseline), platelet normalisation, estimated
glomerular filtration rate (eGFR) increase and plasma exchange/plasma infusion (PE/PI)-free
status.
RESULTS: 22 pts were enrolled (mean age 6.5 years [range, 1 month to 17 years]; 10 [45%]
females; 10 [45%] with an identified complement mutation or antibody). 16 (73%) pts were
newly diagnosed with aHUS (a median of 6 days prior to Ecu treatment). 19 (86%) pts
completed 26 weeks of Ecu treatment. Outcomes improved as shown in Table 1. Dialysis was
discontinued by 9/11 (82%) pts receiving this at baseline, with the other 11 pts remaining
dialysis free. All 10 pts managed with PE/PI at baseline discontinued PE/PI. Ecu was well
tolerated and no safety concerns became apparent. There were no meningococcal infections and
no deaths.
Table 1. Outcomes in paediatric pts with aHUS at median 26 weeks of Ecu treatment
Complete TMA response, n (%)
14 (64%) 95% CI 41-83
Platelet normalisation, n (%)
21 (95%) 95% CI 77-100
eGFR increase of ≥15 mL/min/1.73m2 from baseline, n (%)
19 (86%) 95% CI 65-97
Mean (95% CI) eGFR increase from baseline,
64 (50, 79); P<0.0001, week 27
mL/min/1.73m2
CONCLUSION: This first prospective trial of Ecu treatment in paediatric pts with aHUS
confirmed inhibition of complement-mediated TMA. Early intervention with Ecu improved
haematologic and renal parameters, and decreased the burden of dialysis. In paediatric pts with
aHUS, treatment with Ecu as first-line therapy is effective and well tolerated at the approved
dose regimen. The clinical trial is continuing.