Safety and Efficacy of Canakinumab Prefilled Syringes in Frequently Flaring Acute Gouty Arthritis Patients

Study Overview
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Brief Summary
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This study assessed the safety and efficacy of canakinumab pre-filled syringes in comparison to triamcinolone acetonide 40 mg and canakinumab lyophilizate in patients that have frequent flares of acute gouty arthritis.

Official Title
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A Randomized, Double-blind, Active-controlled Study of Canakinumab Prefilled Syringes or Reconstituted Lyophilizate Versus Triamcinolone Acetonide for Treating Acute Gouty Arthritis Flares in Frequently Flaring Patients

Conditions
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Acute Gouty Arthritis

Intervention / Treatment
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* Drug: Canakinumab pre-filled syringe
* Drug: Canakinumab lyophilized powder
* Drug: Triamcinolone Acetonide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 3 or more gout flares within last year Contraindication, intolerance or lack of efficacy for NSAIDs and/or colchicine Body mass index of less than or equal to 45 kg/m2 Exclusion criteria: Use of the following therapies (within varying protocol defined timeframes): corticosteroids, narcotics, topical ice/cold packs, chronic opiate treatment, NSAIDs (such as aspirin), colchicine. Hemodialysis Live vaccine within 3 months before first dose Donation or loss of 400 mL or more within 3 months before first dose Gout brought on by other factors such as chemotherapy, lead, transplant, etc. Presence of other acute inflammatory arthritis such as Rheumatoid Arthritis Any conditions or significant medical problems that puts the patient at an unacceptable immunological risk to receive this type of therapy such as HIV, Hepatitis, Tuberculosis and other infections/conditions Significant cardiovascular conditions such as uncontrolled hypertension Significant medical diseases such as uncontrolled diabetes, thyroid disease History of malignancy of any organ system within the past 5 years Women who are pregnant or nursing 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, pre-filled syringes (PFS)<br>Patients on this arm received 150 mg subcutaneously (s.c.) at randomization and upon new flare. The doses were provided as pre-filled syringes. The patients were given 3 injections: two placebo and one active drug. | Drug: Canakinumab pre-filled syringe<br>* Canakinumab pre-filled syringe<br>Drug: Placebo<br>* Matching placebo to Canakinumab (PFS), Canakinumab (LYO) and Triamcinolone Acetonide<br>|
| Active Comparator: Canakinumab, lyophilizate (LYO)<br>The patients on this arm received 150 mg s.c. at randomization and upon new flare. The doses were provided as lyophilized powder and had to be reconstituted with water for injection before application. The patients were given 3 injections: two placebo and one active drug. | Drug: Canakinumab lyophilized powder<br>* Canakinumab lyophilized powder<br>Drug: Placebo<br>* Matching placebo to Canakinumab (PFS), Canakinumab (LYO) and Triamcinolone Acetonide<br>|
| Active Comparator: Triamcinolone Acetonide<br>The patients on this arm received 40 mg intramuscular (i.m.) at randomization and upon new flare. The patients were given 3 injections: two placebo and one active drug. | Drug: Triamcinolone Acetonide<br>* Triamcinolone Acetonide<br>Drug: Placebo<br>* Matching placebo to Canakinumab (PFS), Canakinumab (LYO) and Triamcinolone Acetonide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity on a 0-100 mm Visual Analog Scale (VAS) Between the Canakinumab 150 mg PFS and Triamcinolone Acetonide 40 mg Groups | The Visual Analog Scale (VAS) is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two end points whereby the respondent places a mark on the line to indicate his or her response. In this study, patients scored their pain intensity in the most affected joint of the gout flare on a 0 100 mm VAS. The scale ranged from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. Missing pain intensity data at 72 hours was imputed using the Last-Observation-Carried-Forward (LOCF) method. | 72 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity on a 0 - 100 mm VAS Between the Canakinumab 150 mg PFS and Canakinumab 150 mg LYO Groups | The Visual Analog Scale (VAS) is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two end points whereby the respondent places a mark on the line to indicate his or her response. In this study, patients scored their pain intensity in the most affected joint of the gout flare on a 0 100 mm VAS. The scale ranged from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. Missing pain intensity data at 72 hours was imputed using the Last-Observation-Carried-Forward (LOCF) method. | 72 hours post dose | 
| Patient's Assessment of Pain Intensity on a 0-100mm VAS | The Visual Analog Scale (VAS) is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two end points whereby the respondent places a mark on the line to indicate his or her response. In this study, patients scored their pain intensity in the most affected joint of the gout flare on a 0 100 mm VAS. The scale ranged from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. The LOCF method was used to impute post-dose pain intensity VAS measurements up to 14 days. | 14 days | 
| Patient's Assessment of Pain Intensity on a 5-point Likert Scale | A Likert scale is a type of scale with a range of responses corresponding to an item such as pain. The respondent selects the best response that indicates the respondent's subjective evaluation of the item. Patients scored their pain intensity in the most affected joint of the gout flare on a 5-point Likert scale (none, mild, moderate, severe, extreme). The scores were measured to the nearest millimeter from the left. The LOCF method was used to impute post-dose pain intensity Likert measurements up to 14 days. | 72 hours | 
| Number of Patients With at Least One New Gouty Arthritis Flare After Baseline | Patients met the definition of a new flare if they had: a flare in a joint, which was not a previously affected joint (at baseline or during the study), or a flare in a joint previously affected (at baseline or during the study) after the previous flare in that joint had resolved completely according to the patient's perception. Patients did NOT meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely. | 12 weeks | 
| Time to the First New Gouty Arthritis Flare | Patients met the definition of a new flare if they had: a flare in a joint, which was not a previously affected joint (at baseline or during the study), or a flare in a joint previously affected (at baseline or during the study) after the previous flare in that joint had resolved completely according to the patient's perception. Patients did NOT meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely. Less than 50% of patients had new flares. Therefore, the median time to new flare could not be calculated. | 12 weeks | 
| Time to 50% Reduction in Baseline Pain on a 0 - 100 VAS | The Visual Analog Scale (VAS) is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two end points whereby the respondent places a mark on the line to indicate his or her response. In this study, patients scored their pain intensity in the most affected joint of the gout flare on a 0 100 mm VAS. The scale ranged from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. Kaplan Meier estimate of time to 50% reduction in baseline pain, along with associated 95% confidence interval, were reported. | 14 days | 
| Time to Resolution of Gouty Arthritis Flare as Reported by Patient | Patients completed diary entries at 6, 12, 24, 48 and 72 hours post dose and then daily up to 7 days post-dose and/or daily until resolution of the flare. Kaplan Meier estimate of time to resolution of gouty flare as reported by patient, along with associated 95% confiedence interval, were reported. | 14 days | 
| Patient's Global Assessment of Response to Treatment on a 5-point Likert Scale | A Likert scale is a type of scale with a range of responses corresponding to an item such as pain. The respondent selects the best response that indicates the respondent's subjective evaluation of the item. Patients scored their response to treatment on a 5-point Likert scale (excellent, good, acceptable, slight, poor). This outcome measure shows the number of patients indicating each score on the scale. | 72 hours | 
| Physician's Global Assessment of Response to Treatment on a 5 Point Likert Scale | A Likert scale is a type of scale with a range of responses corresponding to an item such as pain. The respondent selects the best response that indicates the respondent's subjective evaluation of the item. Study physicians scored their assessment of the patients' response to treatment on a 5-point Likert scale (very good, good, fair, poor, very poor). | 72 hours | 
| Physician's Assessment of Tenderness | The study physician assessed the most affected joint for tenderness. Tenderness was measured on a 0 - 3 point scale as follows: 0 = no pain, 1 = patient states that there is pain, 2 = patient states there is pain and winces and 3 = patient states there is pain, winces and withdraws on palpation or passive movement of the affected study joint. | 72 hours | 
| Physician's Assessment of Swelling | The study physician assessed the most affected joint for swelling. Swelling was measured on a 0 - 3 point scale as follows: 0 = no swelling, 1 = palpable, 2= visible and 3 = bulging beyond the joint margins. | 72 hours | 
| Physician's Assessment of Erythema | The study physician assessed the most affected joint for erythema. Erythema was assessed as present, absent or not assessable. | 72 hours | 
| Physician's Assessment of Range of Motion of the Most Affected Joint | The study physician assessed the patient's range of motion of the most affected joint on a 5 point Likert scale (normal, mildly restricted, moderately restricted, severely restricted and immobilized). | 72 hours | 
| Proportion of Patients With Rescue Medication Intake | Patients used a diary to record the time of intake of rescue medication and the amount taken. | 12 weeks | 
| Time to First Rescue Medication Intake | Patients used a diary to record the time of intake of rescue medication and the amount taken. | 14 days | 
| Amount of Rescue Medication Taken (mg) | Patients used a diary to record the time of intake of rescue medication and the amount taken. | 14 days | 
| C-reactive Protein Level | A central laboratory was used for analysis of all blood samples collected. | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gout, arthritis, gout flare, acute gout, gouty, rheumatic disease, uric acid