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SAT0522 Canakinumab Pharmacokinetics in Patients Younger Than 2 Years Old with Cryopyrin Associated Periodic Syndromes
  1. J. Kalabus1,
  2. Y. Uziel2,
  3. P. Brogan3,
  4. M. Hofer4,
  5. J. Kuemmerle-Deschner5,
  6. B. Lauwerys6,
  7. A. Speziale7,
  8. R. Laxer8,
  9. H. Lachmann9,
  10. H. Sun10,
  11. K. Abrams10,
  12. K. Leon10,
  13. G. Junge10
  1. 1Novartis Institutes for Biomedical Research, New Jersey, United States
  2. 2Department of Pediatrics, Meir Medical Center, Israel, Kfar Saba, Israel
  3. 3Department of Paediatric Rheumatology, UCL Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom
  4. 4Unité romande de rhumatologie pédiatrique, Hospitalier Universitaire Vaudois, Lausanne, Switzerland
  5. 5University Hospital, Tuebingen, Germany
  6. 6Cliniques Universitaires Saint-Luc and Université catholique de Louvain, Brussels, Belgium
  7. 7Novartis Pharma AG, Basel, Switzerland
  8. 8University of Toronto, Staff Rheumatologist, The Hospital for Sick Children, Toronto, Ontario, Canada
  9. 9National Amyloidosis Centre, UCL Medical School, London, United Kingdom
  10. 10Novartis Pharmaceuticals Corporation, New Jersey, United States

Abstract

Background Canakinumab (CAN) has demonstrated efficacy in patients with Cryopyrin-Associated Periodic Syndromes (CAPS) ≥2 yrs of age1. However, no information on the pharmacokinetics (PK) of CAN in patients 2 yrs of age is available. We present preliminary PK data from a phase III study in this patient population.

Objectives Primary objective was to assess the efficacy of CAN with respect to the treatment response in CAPS patients ≤4 yrs of age. A secondary endpoint was to evaluate PK and pharmacodynamics (PD) profiling of CAN.

Methods CAN-naïve patients with confirmed CAPS aged 44 days to 4 yrs received open-label CAN dosed 2-12 mg/kg every 4 or 8 weeks for 56 weeks. For NOMID patients, an initial dose of 4 mg/kg was administered. Patients who did not achieve complete response following CAN injection, or experienced a flare before the next planned administration, were eligible for dose up-titration with possible maintenance and step-wise up-titration regimens of 4, 6, 8, 10, or 12 mg/kg s.c.

Results Seventeen patients, 6 patients <24 months old (44 days to 14 months; mean age =7 month), were enrolled and administered body weight-based (2 mg/kg to 10 mg/kg) doses of CAN s.c. every 8 weeks, with the exception of one patient who received doses of 4-6 mg/kg once weekly. Patients received more than one dose during the study. Of the 6 patients <24 months old, 5 were dosed with 2 mg/kg at each dose, 1 NOMID patient started with 4 mg/kg and up-titrated to 8 mg/kg at last dose. The efficacy observed in this trial was consistent with efficacy reported in studies of older patients. Sixteen patients achieved a complete response, with 7 patients requiring dose escalation to achieve and/or maintain their responses. Dose-normalized mean CAN trough concentrations at steady-state (Css, trough) in the patients <24 months old were similar across the 6 patients from 44 days to 15 months, while the range of exposures as represented by the dose-normalized trough levels (Css,trough) overlapped with the remaining 11 study patients >2 yrs old who received CAN doses ranging from 2–10 mg/kg. The safety profile for patients <24 months was similar to that observed for older patients and the overall study safety profile was similar to that observed in the pivotal program.

Conclusions Canakinumab is a highly effective treatment for patients with CAPS aged as young as 44 days old. The preliminary PK results demonstrated that dose-normalized canakinumab exposure in patients <2 yrs old was similar to patients >2 yrs supporting the utilization of weight-based dosing in the CAPS infantile population.

References

  1. Lachmann H, et al. N Engl J Med. 2009;60:2416-25.

Disclosure of Interest J. Kalabus Employee of: Novartis, Y. Uziel Consultant for: Novartis, Speakers bureau: Novartis, P. Brogan Grant/research support from: Institutional grant support to undertake the study described in this abstract, Consultant for: SOBI and Roche, M. Hofer Consultant for: Novartis, J. Kuemmerle-Deschner Grant/research support from: Novartis, Consultant for: Novartis, B. Lauwerys: None declared, A. Speziale Employee of: Novartis, R. Laxer Grant/research support from: Database funding from Novartis, Consultant for: Participant in Ad Board for Novartis, H. Lachmann Consultant for: Novartis, Speakers bureau: Novartis, H. Sun Employee of: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, K. Leon Employee of: Novartis, G. Junge Employee of: Novartis

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