Efficacy and Safety of a Single Dose of Canakinumab (ACZ885) in Hospitalized Patients With Acute Gout

Study Overview
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Brief Summary
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This is an exploratory proof-of-concept study to evaluate the safety and efficacy of canakinumab (ACZ885) for inflammation and pain associated with acute gouty arthritis.

Official Title
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A Randomized, Double-blind, Double-dummy, Active-controlled, Parallel Group Study of a Single Dose of ACZ885 in Hospitalized Patients With Acute Gout

Conditions
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Arthritis, Gouty

Intervention / Treatment
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* Biological: canakinumab
* Drug: dexamethasone
* Other: placebo matching canakinumab
* Other: placebo matching dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: score over 50 on the 0-100 VAS pain scale acute, confirmed gout flare for no longer than 3 days Exclusion Criteria: Treatment with biological anti-tumor necrosis factor (anti-TNF) within the past 3 months Anti-inflammatory medication for the treatment of acute gout within the previous 24 hours Pregnant or breastfeeding women Major surgery with high infection risk History of severe allergy to food or drugs History or risk of tuberculosis Active infection Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canakinumab<br>Canakinumab 10 mg/kg intravenous infusion and placebo matching dexamethasone intravenous infusion on Day 1. | Biological: canakinumab<br>* 10 mg/kg intravenous infusion 250 mL over 2 hours.<br>* Other names: Ilaris®;Other: placebo matching dexamethasone<br>* Placebo intravenous infusion.<br>|
| Active Comparator: Dexamethasone<br>Dexamethasone 12 mg intravenous infusion and placebo matching canakinumab on Day 1. | Drug: dexamethasone<br>* 12 mg intravenous infusion 50 mL over 30 minutes.<br>Other: placebo matching canakinumab<br>* 5% glucose in water intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Improvement in Gout at 72 Hours Post-dose Using a Likert Scale | 72 hours following treatment, patients were asked the question: How would you rate the improvement in your gout since receiving the study medication? Patients rated their improvement on the Likert 5-point scale: 1=Excellent, 2=Good, 3=Acceptable,4=Slight and 5=Poor. Improvement was assessed by determining patients who scored a good or excellent response. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-inferiority of a Single Dose of Canakinumab Compared to Dexamethasone During Treatment Period |  | 72 hours | 
| Time to Recurrence of the Symptoms of Acute Gout (if Applicable) During Treatment Period | Time to recurrence is defined as from the point of improvement (good to excellent on Likert scale) to recurrence. | 4 months | 
| Time to Walk Independently (if Applicable) During Treatment Period |  | 4 months | 
| Number of Participants With Discontinuation of Treatment Due to Adverse Events, Deaths or Serious Adverse Events During the Study | Additional safety information can be found in the Adverse Event section. | 4 months | 
| Change in C-reactive Protein (CRP) From Baseline at Month 4 | Blood was collected at Baseline and Month 4 for CRP to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A negative change from baseline indicates improvement. | Baseline, Month 4 | 
| Change in Serum Amyloid A Protein (SAA) From Baseline at Month 4 | Blood was collected at Baseline and Month 4 for SAA to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A negative change from baseline indicates improvement. | Baseline, Month 4 | 
| ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period | Blood was collected for ACZ885 (canakinumab) levels at baseline and Days 0.25, 1, 3, 6, 20, 34, 55 and 119. Serum was analyzed by means of a competitive Enzyme linked immunosorbant assay (ELISA). | Baseline, Days 0.25, 1, 3, 6, 20, 34, 55 and 119 | 
| Change From Baseline in Pain Using a Visual Analog Scale at Month 4 | Patients rated their pain on a 100 millimeter (mm) visual analog scale, ranging from no pain (0) to unbearable pain (100). A negative change from baseline indicates improvement. | Baseline, Month 4 | 
| Number of Patients Who Took Rescue Medication | Patients who did not improve by 72 hours post-dose (i.e. patients who show a pain Visual Analog (VAS) decrease of less than 50 % from baseline (Day 1, pre-dose) would have been treated with rescue medication of methylprednisolone 80 mg intravenous or intramuscular once at the discretion of the clinical investigator. | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arthritis Gouty, ACZ885, IL1B protein, Pain