An open-label extension study of CACZ885H2357E1 on the treatment and prevention of gout flares in patients with frequent flares for whom NSAIDs and/ or colchicine are contraindicated, not tolerated or ineffective

Gout is the most common form of inflammatory joint disease in men over the age
of 40 years . It is estimated to affect 0.5-2.8% of men, with a lower rate of
occurrence among women, who experience gout, primarily, after menopause. The
most common clinical finding in these patients is a sudden onset of an acute
gout flare (also referred to as acute gout attack), which is a severe arthritis
(monoarticular/ oligoarticular/ polyarticular) in any joints in the body,
predominantly seen in a peripheral joint in the leg.
Several lines of evidence suggest that gout inflammation is primarily IL-1β
driven and therefore, inflammation in gout may be significantly attenuated with
a selective blockade of IL-1β. In line with this, anakinra, an IL-1 receptor
antagonist, significantly relieved the pain of acute gout flares in patients
who could not tolerate or had failed standard anti-inflammatory therapies for
gouty arthritis. Moreover, rilonacept (IL-1 trap), an IL-1 inhibitor decreased
the disease activity and pain in patients with chronic active gout and also
reduced the occurrence of new gout flares that are often seen during initiation
of urate-lowering therapy.
Canakinumab (ACZ885) is a fully human monoclonal anti-human IL-1β antibody. It
is designed to bind to human IL-1β and thus blocks the interaction of this
cytokine with its receptors. This results in neutralized bioactivity of IL-1β,
but does not prevent the binding of the natural inhibitor, IL-1Ra, nor binding
to IL-1α. Detailed background information on the chemistry, pharmacology,
toxicology, preclinical and clinical data of canakinumab is also given in the
Investigator*s Brochure. Results of a single-dose, 8-week Phase II study
(CACZ885H2255) in gout patients that were refractory and/ or contraindicated to
NSAIDs and/ or colchicine indicated that canakinumab at the selected dose of
150 mg subcutaneously (s.c.) was more effective in treating patient*s pain at
the time of acute gout flares and also in preventing the occurrence of new gout
flares as compared to triamcinolone acetonide 40 mg intramuscularly (i.m.).
This is the 2nd follow-up study (open label, non-comparative), open to patients
who have completed the study CACZ885H2357 (canakinumab vs triamcinolon
acetonide, 12 weeks) and the 1st follow-up study (CACZ885H2357E1).

Primary: Long term safety and tolerability.
Secondary: Time to 1st flare, number and severity of flares, efficiacy in
treating flares, effect on inflammatory markers, immunogenicity, PK.

Multicenter open label, non-comparative phase III study.
Patients who have successfully completed the preceding studies CACZ885H2357 and
CACZ885H2357E1 of who have experienced too many flares in the preceding study
may participate. In case of a new flare, they will be treated with a single
dose of canakinumab 150 mg subcutaneously.
Study duration 1 year.
Pain killer to be used if needed: paracetamolmol (max. 3 g daily) or codeïne
(max. 180 mg daily) , s.n. prednisolon.
150-200 patients.

Treatment with canakinumab in case of gout flare.

Risk: Adverse effects of study medication.
Burden: 4 visits in 1 year (NB 1st visit = last visit of preceding study).
All visits: fasting, blood tests (approx 20 ml/visit, total volume: 85 ml) and
questionnaires (VAS, Likert scale, global evaluation, gout questionnaire,
EQ-5D, HAQ-DI or SF-36, work-productivity questionnaire); estimated completion
time 15-20 minutes per visit. In case of flare and study drug administration 7
visits in 3 months and 80 mls of blood extra.
In addition: Physical examination (4x), ECG (2x), pregnancy test (2x), diary
(use of pain killers, symptoms).
In selected centres: Doppler examination joints (4x).