Efficacy and Safety of Canakinumab in Patients with Periodic Fever Syndromes (Colchicine-Resistant FMF, HIDS/MKD and TRAPS): Results from a Phase 3, Pivotal, Umbrella Trial

Fabrizio De Benedetti¹, Jordi Anton², Eldad Ben-Chetrit³, Inmaculada Calvo⁴, Joost Frenkel⁵, Marco Gattorno⁶, Hal M. Hoffman⁷, Ozgur Kasapcopur⁸, Isabelle Koné-Paut⁹, Helen Lachmann¹⁰, Michel Moutschen¹¹, Seza Ozen¹², Pierre Quartier¹³, Anna Simon¹⁴, Andrew Zeft¹⁵, Karine Lheritier¹⁶, Antonio Speziale¹⁶ and Guido Junge¹⁶, ¹IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, ²Unitat de Reumatologia Pediàtrica, Hospital Sant Joan de Déu, Barcelona, Spain, ³Rheumatology Unit, Hadassah—Hebrew University Medical Center, Jerusalem, Israel, ⁴Hospital Universitario y Polytecnico La Fe, Valencia, Spain, ⁵University Medical Center,Utrecht, Utrecht, Netherlands, ⁶Pediatric Rheumatology, G. Gaslini Institute, Genoa, Italy, ⁷Division of Rheumatology, Allergy, and Immunology, University of California at San Deigo, La Jolla, CA, ⁸Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey, ⁹Hopital Kremlin Bicetre, University of Paris SUD, Paris, France, ¹⁰UK National Amyloidosis Centre, University College London Medical School, London, United Kingdom, ¹¹CHU de Liège/ University of Liège, Liège, Belgium, ¹²Department of Pediatrics, Hacettepe University, Ankara, Turkey, ¹³Necker-Enfants Malades Hospital, Paris, France, ¹⁴National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, ¹⁵Pediatrics Rheumatology, Cleveland Clinic, Cleveland, OH, ¹⁶Novartis Pharma AG, Basel, Switzerland

Meeting: Pediatric Rheumatology Symposium 2017

Keywords: canakinumab and familial Mediterranean fever

Session Information

Date: Thursday, May 18, 2017

Title: Clinical and Therapeutic Poster Breakout I

Session Type: Abstract Submissions

Session Time: 4:45PM-5:15PM

Background/Purpose: Open-label studies have suggested the efficacy of canakinumab (CAN), a fully human, highly specific anti-IL-1β neutralizing monoclonal antibody, in colchicine-resistant-FMF (crFMF), hyper-immunoglobulin (Ig) D syndrome/mevalonate kinase deficiency (HIDS/MKD), and tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS).^1-3 We report the efficacy and safety of CAN from the randomized treatment epoch of the Phase 3 pivotal study in patients (pts) with crFMF, HIDS/MKD or TRAPS.

Methods: The study (NCT02059291) consists of 3 disease cohorts (crFMF, HIDS /MKD and TRAPS) and 4 study epochs: a screening epoch (E1) of up to 12 wks, a randomized treatment epoch (E2) of 16 wks, a randomized withdrawal epoch (E3) of 24 wks and an open-label treatment epoch (E4) of 72 wks. Pts (aged ≥2 years) with a flare during E1were randomized (1:1) in E2 to receive CAN or placebo (PBO). Primary objective was to demonstrate that CAN 150 mg (or 2 mg/kg for pts ≤40 kg) sc q4w is superior to PBO. Safety assessments included adverse events (AEs) and serious AEs(SAEs).

Results: Of 181 pts (crFMF, n=63; HIDS/MKD, n=72; TRAPS, n=46) randomized in E2, 6 discontinued the study (5 PBO; 1 CAN). In all 3 disease cohorts, the proportion of responders for the primary outcome at Wk 16 was significantly higher with CAN vs PBO. At Wk 16, a significantly higher proportion of pts achieved a physician’s global assessment (PGA) score <2, C-reactive protein (CRP) ≤10 mg/L and serum amyloid A (SAA) ≤10 mg/L in the CAN group vs PBO in all 3 cohorts. The most frequently affected system organ class across 3 cohorts was infections and infestations typically involving the upper respiratory tract. The incidence of SAEs was 8.6%, 4.7% and 11.8% in crFMF, TRAPS and HIDS/MKD cohorts, respectively.

Conclusion: These results demonstrated superior efficacy of canakinumab after a 16-week treatment period compared with placebo. The overall safety profile was not distinct from those reported in previous controlled studies.

References:

1. Brik R, et al. Ann Rheum Dis. 2013;72:75.
2. Arostegui J, et al. Ann Rheum Dis. 2015;74:401.
3. Lachmann H, et al. Ann Rheum Dis.2015;74:852.

Disclosure: F. De Benedetti, 2; J. Anton, 2,5; E. Ben-Chetrit, 5; I. Calvo, 2,8; J. Frenkel, 2; M. Gattorno, 2,5; H. M. Hoffman, 5,8; O. Kasapcopur, 8; I. Koné-Paut, 2,8; H. Lachmann, 5,8; M. Moutschen, None; S. Ozen, 8; P. Quartier, 2,5,8; A. Simon, 2,5; A. Zeft, 1,5; K. Lheritier, 1,3; A. Speziale, 3; G. Junge, 3.

To cite this abstract in AMA style:

De Benedetti F, Anton J, Ben-Chetrit E, Calvo I, Frenkel J, Gattorno M, Hoffman HM, Kasapcopur O, Koné-Paut I, Lachmann H, Moutschen M, Ozen S, Quartier P, Simon A, Zeft A, Lheritier K, Speziale A, Junge G. Efficacy and Safety of Canakinumab in Patients with Periodic Fever Syndromes (Colchicine-Resistant FMF, HIDS/MKD and TRAPS): Results from a Phase 3, Pivotal, Umbrella Trial [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 4). https://acrabstracts.org/abstract/efficacy-and-safety-of-canakinumab-in-patients-with-periodic-fever-syndromes-colchicine-resistant-fmf-hidsmkd-and-traps-results-from-a-phase-3-pivotal-umbrella-trial-2/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-canakinumab-in-patients-with-periodic-fever-syndromes-colchicine-resistant-fmf-hidsmkd-and-traps-results-from-a-phase-3-pivotal-umbrella-trial-2/