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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Gouty Arthritis
• Intervention / Treatment: Drug: Canakinumab pre-filled syringe; Drug: Placebo; Drug: Canakinumab lyophilized powder; Drug: Triamcinolone Acetonide

• Study Type: Interventional
• Enrollment (Actual): 397
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Newfoundland and Labrador
    • St-John's, Newfoundland and Labrador, Canada, A1E 2C2
      • Novartis Investigative Site
    • St. John, Newfoundland and Labrador, Canada, A1B 5E8
      • Novartis Investigative Site
  • Ontario
    • Toronto, Ontario, Canada, M9W 4L6
      • Novartis Investigative Site
  • Quebec
    • Sainte-Foy, Quebec, Canada, G1v 3M7
      • Novartis Investigative Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0H6
      • Novartis Investigative Site
• Germany
  • Bad Doberan, Germany, 18209
    • Novartis Investigative Site
  • Bayreuth, Germany, 95445
    • Novartis Investigative Site
  • Berlin, Germany, 13125
    • Novartis Investigative Site
  • Loehne, Germany, 32584
    • Novartis Investigative Site
  • Magdeburg, Germany, 39110
    • Novartis Investigative Site
  • Messkirch, Germany, 88605
    • Novartis Investigative Site
  • Regensburg, Germany, 93053
    • Novartis Investigative Site
  • Weener, Germany, 26826
    • Novartis Investigative Site
  • Zwiesel, Germany, 94227
    • Novartis Investigative Site
• Hungary
  • Bekescsaba, Hungary, H-5600
    • Novartis Investigative Site
  • Budapest, Hungary, 1023
    • Novartis Investigative Site
  • Budapest, Hungary, 1027
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Eger, Hungary, 3300
    • Novartis Investigative Site
  • Gyula, Hungary, 5703
    • Novartis Investigative Site
  • Kistarcsa, Hungary, 2143
    • Novartis Investigative Site
  • Szikszo, Hungary, 3800
    • Novartis Investigative Site
  • Szolnok, Hungary, 5000
    • Novartis Investigative Site
  • Veszprem, Hungary, H-8200
    • Novartis Investigative Site
• Lithuania
  • Klaipeda, Lithuania, 92288
    • Novartis Investigative Site
  • Vilnius, Lithuania, LT-08661
    • Novartis Investigative Site
  • Vilnius, Lithuania, 09020
    • Novartis Investigative Site
  • LT
    • Kaunas, LT, Lithuania, 50128
      • Novartis Investigative Site
    • Kaunas, LT, Lithuania, 51349
      • Novartis Investigative Site
    • Vilnius, LT, Lithuania, 01117
      • Novartis Investigative Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207-5710
      • Novartis Investigative Site
    • Gulf Shores, Alabama, United States, 36547
      • Novartis Investigative Site
    • Mobile, Alabama, United States, 36608
      • Novartis Investigative Site
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Novartis Investigative Site
    • Phoenix, Arizona, United States, 85013
      • Novartis Investigative Site
    • Scottsdale, Arizona, United States, 85251
      • Novartis Investigative Site
  • California
    • Buena Park, California, United States, 90620
      • Novartis Investigative Site
    • Fair Oaks, California, United States, 95628
      • Novartis Investigative Site
    • Norwalk, California, United States, 90650
      • Novartis Investigative Site
    • Orangevale, California, United States, 95662
      • Novartis Investigative Site
    • Pasadena, California, United States, 91105
      • Novartis Investigative Site
    • Westlake Village, California, United States, 91361
      • Novartis Investigative Site
  • Florida
    • Clearwater, Florida, United States, 33756
      • Novartis Investigative Site
    • Jupiter, Florida, United States, 33458
      • Novartis Investigative Site
    • Largo, Florida, United States, 33773
      • Novartis Investigative Site
    • South Miami, Florida, United States, 33143
      • Novartis Investigative Site
  • Georgia
    • Augusta, Georgia, United States, 30904
      • Novartis Investigative Site
    • Decatur, Georgia, United States, 30035
      • Novartis Investigative Site
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Novartis Investigative Site
  • Kansas
    • Overland Park, Kansas, United States, 66215
      • Novartis Investigative Site
    • Topeka, Kansas, United States, 66606
      • Novartis Investigative Site
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Novartis Investigative Site
    • Owensboro, Kentucky, United States, 42303
      • Novartis Investigative Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Novartis Investigative Site
  • Michigan
    • Troy, Michigan, United States, 48085
      • Novartis Investigative Site
  • Mississippi
    • Belzoni, Mississippi, United States, 39038
      • Novartis Investigative Site
    • Jackson, Mississippi, United States, 39202
      • Novartis Investigative Site
    • Jackson, Mississippi, United States, 39209
      • Novartis Investigative Site
    • Picayune, Mississippi, United States, 39466
      • Novartis Investigative Site
  • Montana
    • Missoula, Montana, United States, 59804
      • Novartis Investigative Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Novartis Investigative Site
    • Omaha, Nebraska, United States, 68114
      • Novartis Investigative Site
    • Omaha, Nebraska, United States, 68134
      • Novartis Investigative Site
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • Novartis Investigative Site
  • New York
    • Mineola, New York, United States, 11501
      • Novartis Investigative Site
    • New Hyde Park, New York, United States, 11042
      • Novartis Investigative Site
    • Roslyn, New York, United States, 11576
      • Novartis Investigative Site
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Novartis Investigative Site
    • Cary, North Carolina, United States, 27518
      • Novartis Investigative Site
    • Charlotte, North Carolina, United States, 28277
      • Novartis Investigative Site
    • Charlotte, North Carolina, United States, 28209
      • Novartis Investigative Site
    • Greensboro, North Carolina, United States, 27401
      • Novartis Investigative Site
    • Greensboro, North Carolina, United States, 27408
      • Novartis Investigative Site
    • Salisbury, North Carolina, United States, 28144
      • Novartis Investigative Site
    • Shelby, North Carolina, United States, 28152
      • Novartis Investigative Site
    • Wilmington, North Carolina, United States, 28401
      • Novartis Investigative Site
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Novartis Investigative Site
  • Ohio
    • Mogadore, Ohio, United States, 44260
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Novartis Investigative Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Novartis Investigative Site
  • South Carolina
    • Charleston, South Carolina, United States, 29412
      • Novartis Investigative Site
    • Columbia, South Carolina, United States, 29204
      • Novartis Investigative Site
    • Greer, South Carolina, United States, 29651
      • Novartis Investigative Site
    • Murrells Inlet, South Carolina, United States, 29576
      • Novartis Investigative Site
    • Ninety Six, South Carolina, United States, 29666
      • Novartis Investigative Site
    • Varnville, South Carolina, United States, 29944
      • Novartis Investigative Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Novartis Investigative Site
    • Fayetteville, Tennessee, United States, 33734
      • Novartis Investigative Site
    • Johnson City, Tennessee, United States, 37601
      • Novartis Investigative Site
    • Memphis, Tennessee, United States, 38125
      • Novartis Investigative Site
  • Texas
    • Bedford, Texas, United States, 76021
      • Novartis Investigative Site
    • Dallas, Texas, United States, 75231
      • Novartis Investigative Site
    • Houston, Texas, United States, 77034
      • Novartis Investigative Site
  • Utah
    • Bountiful, Utah, United States, 84010
      • Novartis Investigative Site
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Novartis Investigative Site
    • Danville, Virginia, United States, 24541
      • Novartis Investigative Site
    • Midlothian, Virginia, United States, 23114
      • Novartis Investigative Site
    • Newport News, Virginia, United States, 23606
      • Novartis Investigative Site
  • Washington
    • Bellevue, Washington, United States, 98004
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Canakinumab, pre-filled syringes (PFS); 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; Canakinumab pre-filled syringe; Drug: Placebo; Matching placebo to Canakinumab (PFS), Canakinumab (LYO) and Triamcinolone Acetonide
ACTIVE_COMPARATOR: Canakinumab, lyophilizate (LYO); 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: Placebo; Matching placebo to Canakinumab (PFS), Canakinumab (LYO) and Triamcinolone Acetonide; Drug: Canakinumab lyophilized powder; Canakinumab lyophilized powder
ACTIVE_COMPARATOR: Triamcinolone Acetonide; 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: Placebo; Matching placebo to Canakinumab (PFS), Canakinumab (LYO) and Triamcinolone Acetonide; Drug: Triamcinolone Acetonide; Triamcinolone Acetonide

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (ACTUAL): September 1, 2012
• Study Completion (ACTUAL): September 1, 2012

Study Registration Dates

• First Submitted: May 16, 2011
• First Submitted That Met QC Criteria: May 18, 2011
• First Posted (ESTIMATE): May 19, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): January 29, 2014
• Last Update Submitted That Met QC Criteria: December 10, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Gout; uric acid; arthritis; acute gout; rheumatic disease; gout flare; gouty
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Gout; Arthritis; Arthritis, Gouty; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triamcinolone; Antibodies, Monoclonal; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: CACZ885H2361; 2010-024173-39 (EUDRACT_NUMBER)