Article
Pharmacokinetics of Canakinumab treated CAPS Children younger than 2 Years old
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Authors
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Jasmin Kümmerle-Deschner
- Universitätskinderklinik Tuebingen, Rheumatologie, Tübingen
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James Kalabus
- Novartis Institutes for Biomedical Research, New Jersey, New Jersey, USA
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Paul Brogan
- UCL Institute of Child Health, Rheumatologie, London, United Kingdom
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Michael Hofer
- Hospitalier Universitaire Vaudois, Rheumatologie, Lausanne, Switzerland
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Bernard. R. Lauwerys
- Université Catholique de Louvain, Rheumatologie, Brüssel, Belgium
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Antonio Speziale
- Novartis Pharma AG, Immunologie & Dermatologie, Basel, Switzerland
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Ronald Laxer
- University of Toronto, Hospital for Sick Children, Rheumatologie, Toronto, USA
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Haiying Sun
- Novartis Pharmaceuticals Corporation, DMPK-Clinical PK / PD-02, New Jersey, USA
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Ken Abrams
- Novartis Pharmaceuticals Corporation, New Jersey, United States of America
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Karolynn Leon
- Novartis Pharmaceuticals Corporation, New Jersey, I&D Development, Franchise 1, New Jersey, USA
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Guido Junge
- Novartis Pharma AG, Basel, Switzerland
| Published: | September 1, 2015 |
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Outline
Text
Introduction: Canakinumab (CAN) is indicated for the treatment of cryopyrin-associated periodic syndrome (CAPS) in patients ≥2 years of age1. However, information on the pharmacokinetics (PK) of CAN in patients <2 years of age is not available. Here, we present preliminary PK data from a phase III study in CAPS patients.
The objective is to assess the efficacy of CAN with respect to the treatment response in CAPS patients ≤4 years of age and to evaluate PK and pharmacodynamics (PD) profiling of CAN.
Methods: CAN-naïve patients with confirmed CAPS aged 44 days to 4 years received open-label CAN 2 mg/kg every 8 weeks for 56 weeks. For NOMID patients, an initial dose of 4 mg/kg was administered. Patients who did not achieve complete response 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, or 8 mg/kg s.c.
Results: 17 patients, 6 patients <24 months old (44 days to 14 months; mean age = 7 months), were enrolled and administered body weight-based (2 mg/kg up to 12 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. Of the 6 patients <24 months old, 5 were dosed with 2 mg/kg at each dose while 1 NOMID patient started with 4 mg/kg and up-titrated to 8 mg/kg at last dose. Sixteen patients achieved a complete response, with 7 patients requiring dose escalation to achieve and/or maintain their responses. Mean dose-normalized CAN trough concentrations at steadystate in the patients <24 months old were similar across the 6 patients from 44 days to 15 months, while the range of exposures overlapped with the remaining 11 study patients >2 years old who received CAN doses ranging from 2 mg/kg up to12 mg/kg.
Conclusion: Canakinumab is an 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 years old was similar to patients >2 years supporting the utilization of weight-based dosing in the CAPS infantile population.
