Safety & Efficacy of Canakinumab (ACZ885) in Patients With Frequent Flares for Whom Nonsterodial Anti-Inflammatory Drug (NSAIDs) and/ or Colchicine Are Contraindicated, Not Tolerated or Ineffective

Study Overview
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Brief Summary
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The purpose of this pivotal Phase III study is to support the registration of canakinumab for the indication of gout in China, a replicate of global studies CACZ885H2356 & CACZ885H2357 by demonstrating in patients with frequent flares of gout for whom NSAIDs and/or colchicine are contraindicated, not tolerated or ineffective, canakinumab 150 mg s.c. given upon acute gout flares relieves the signs and symptoms and prevents recurrence of gout flares compared to triamcinolone acetonide 40 mg i.m.

Official Title
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A Randomized, Double-blind, Double-dummy, Active Controlled Study of Canakinumab (ACZ885) 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

Conditions
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Gouty Arthritis

Intervention / Treatment
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* Drug: Canakinumab, ACZ885
* Drug: Triamcinolone acetonide


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Meeting diagnosis criteria for acute arthritis of primary gout. Start of acute gout flare within 5 days prior to study visit 1 History of ≥ 3 gout flares within the 12 months prior to study start Evidence of contraindication (absolute or relative), or intolerance, or lack of efficacy for either NSAIDs and/or colchicines Exclusion criteria: Requirement for administration of antibiotics against latent tuberculosis (TB), e.g., isoniazide Refractory heart failure (Stage D). Unstable cardiac arrhythmias or unstable symptomatic coronary ischemia Secondary gout, chemotherapy induced gout, lead induced gout and transplant gout Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canakinumab and placebo matching to triamcinolone acetonide<br>ACZ885H | Drug: Canakinumab, ACZ885<br>* Canakinumab and placebo matching to triamcinolone acetonide<br>|
| Active Comparator: Triamcinolone acetonide 40 mg<br>ACZ885H | Drug: Triamcinolone acetonide<br>* Triamcinolone acetonide 40 mg and placebo matching to canakinumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in the Gout Pain Intensity in the Target Joint Following ACZ885 Administration Measured by Visual Analog Scale (VAS) | A higher score indicates greater pain intensity. Based on the distribution of pain VAS scores in postsurgical patients (knee replacement, hysterectomy, or laparoscopic myomectomy) who described their postoperative pain intensity as none, mild, moderate, or severe, the following cut points on the pain VAS have been recommended: no pain (0 - 4 mm), mild pain (5- 44 mm), moderate pain (45-74 mm), and severe pain (75- 100 mm) | at 72 hours post-dose | 
| Time to First New Flare: Survival Analysis by Treatment: Kaplan Meier Analysis | Measure canakinumab 150 mg s.c. is superior to triamcinolone acetonide 40 mg i.m. with respect to the time to the first new gout flare in observation period of 12 weeks | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Patients With at Least 1 New Gout Flare |  | 12 weeks | 
| Patients Assessment of Gout Pain Intensity in the Most Effected Joint (0-100mm VAS): Summary Statistics by Timepoint and Treatment | A higher score indicates greater pain intensity. Based on the distribution of pain VAS scores in postsurgical patients (knee replacement, hysterectomy, or laparoscopic myomectomy) who described their postoperative pain intensity as none, mild, moderate, or severe, the following cut points on the pain VAS have been recommended: no pain (0 - 4 mm), mild pain (5- 44 mm), moderate pain (45-74 mm), and severe pain (75- 100 mm) | baseline through 12 weeks | 
| Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale): Frequency Table by Timepoint and Treatment | Patients will score their current pain intensity in the most affected joint of the gout flare on a 5-point Likert scale (none, mild, moderate, severe, extreme). | baseline through week 12 | 
| Patient's Global Assessment of Response to Treatment: Frequency Table by Timepoint and Treatment Using a Likert Scale. | Patients will score their response to pain on a 7-point Likert scale (excellent, good ,acceptable, slight,poor,very poor,not done). | 72 hours through week 12 | 
| Physician's Assessment of Tenderness: Frequency Table by Timepoint and Treatment | Physicians will score their response to pain on a 5-point Likert scale (no pain, pain,pain and winces,pain winces and withdraws and not assessed). | baseline 72 hours,7 days 4 weeks, 8 weeks and 12 weeks post dose | 
| Physician's Assessment of Swelling: Frequency Table by Timepoint and Treatment | Physicians will score their response to pain on a 5-point Likert scale (no pain, pain,pain and winces,pain winces and withdraws and not assessed). | baseline 72 hours,7 days 4 weeks, 8 weeks and 12 weeks post dose | 
| Physician's Assessment of Erythema: Frequency Table by Timepoint and Treatment | Physicians will score their response of erythema on a 4-point Likert scale (absent, present not assessed and not assessable). | baseline 72 hours,7 days 4 weeks, 8 weeks and 12 weeks post dose | 
| Physician's Assessment of Range of Motion: Frequency Table by Timepoint and Treatment | Physicians will score their response ofrange of motion on a 5-point Likert scale (normal,mildly restricted, moderately restricted, severely restricted and immolbilized). | baseline through week 12 | 
| Time to at Least a 50% Reduction in Baseline Pain Intensity: Survival Analysis by Treatment | Kaplan Meier estimate | 12 weeks | 
| Time to Complete Resolution of Pain: Survival Analysis by Treatment | Kaplan Meier estimate | 12 weeks | 
| Time to First Rescue Medication Intake |  | 12 weeks | 
| Percent Patients Who Took Rescue Medication |  | 12 weeks | 
| Amount of Rescue Medication Taken at Baseline Flare and Post Baseline Flare. | Paracetamol / acetaminophen, Prednisolone and Prednisone taken at baseline flare and post baseline flare. | 12 weeks | 
| High Sensitivity C-reactive Protein [hsCRP] Measured in the Serum at 72 Hours Post Dose |  | 72 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gout, Inflammatory gout, acute gout