Clinical trial NCT01080131: Canakinumab in the Treatment of Acute Gout Flares and Prevention of New Flares in Patients Unable to Use Non-steroidal Anti-inflammatory Drugs (NSAIDs) and/or Colchicines Including a 12 Week Extension and a 1 Year Open-label Extension Study.
Official title: A Randomized, Controlled Study of ACZ885 (Canakinumab) 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 Including a 12 Weeks Extension Study and a 1 Year Open-label Extension Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Gout
Keywords: Frequent flares
Gout
Anti-interleukin-1β monoclonal antibody
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-03-03
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to demonstrate that canakinumab given upon acute gout flares relieves the signs and symptoms and prevents recurrence of gout flares in patients with frequent flares of gout for whom non-steroidal anti-inflammatory drugs (NSAIDs) and/ or colchicine are contraindicated, not tolerated, or ineffective. The efficacy of canakinumab was compared to the corticosteroid triamcinolone acetonide.

The purpose of the first 12 week extension study was to collect additional safety, tolerability and efficacy data in patients who have completed the core study CACZ885H2357.

The purpose of the second one year open-label extension study was to confirm the long-term safety and tolerability of canakinumab in patients who had completed the first extension study.


Eligibility criteria: Core Study:

Inclusion criteria:

* Meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of acute arthritis of primary gout
* Onset of current acute gout flare within 5 days prior to study entry
* Baseline pain intensity ≥ 50 mm on the 0-100 mm visual analog scale (VAS)
* History of ≥ 3 gout flares within the 12 months prior to study entry
* Contraindication, or intolerance, or lack of efficacy for non-steroidal anti-inflammatory drugs (NSAID) and/or colchicine

Exclusion criteria:

* Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis
* Presence of severe renal function impairment
* Use of specified pain relief medications or biologics (corticosteroids, narcotics, paracetamol/acetominophen, ibuprofen, colchicine, IL-blocker, and tumor necrosis factor inhibitor within specified periods prior to study entry
* Live vaccinations within 3 months prior to randomization
* Requirement for administration of antibiotics against latent tuberculosis (TB)
* Refractory heart failure (Stage D)
* Unstable cardiac arrhythmias or unstable symptomatic coronary ischemia
* Any active or recurrent bacterial, fungal, or viral infection

Extension Study 1:

Inclusion:

- Completion of the Core study. A patient was defined as completing the core study if they completed the study up to and including visit 7.

Exclusion:

- Continuation in this extension study was considered inappropriate by the treating physician.

Extension Study 2:

Inclusion Criteria:

* Completion of the first extension study CACZ885H2357E1. A patient was defined as completing the first extension study if they completed the study up to and including Visit 10).

Exclusion Criteria:

-Continuation in this second extension study was considered inappropriate by the treating physician.

Other protocol-defined inclusion-exclusion criteria applied to the core and extension studies.

Primary outcomes:
measure: Time to First New Flare: Survival Analysis During the 12 Weeks of Study
timeFrame: Baseline to 12 weeks
measure: Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS) at 72 Hours Post-dose
timeFrame: 72 hours post-dose (randomization)
measure: Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks
timeFrame: During 24 weeks overall
measure: Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall)
timeFrame: 72 weeks
Secondary outcomes:
measure: Time to at Least a 50% Reduction in Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS)
timeFrame: Baseline to 7 days post-dose (randomization)
measure: Time to Complete Resolution of Pain; Survival Analysis
timeFrame: Baseline to 7 days post-dose (randomization)
measure: SF 36 Physical Function Score at Week 12
timeFrame: Week 12
measure: Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks of the Study
timeFrame: Baseline to Week 12
measure: Pharmacokinetic Concentrations
timeFrame: 12 weeks post-dose
measure: Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS)
timeFrame: 6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose (randomization)
measure: Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS)
timeFrame: 6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose for last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
measure: Time to the First New Gout Flare During 24 Weeks
timeFrame: From randomization to the end of the first extension period (24 weeks).
measure: Mean Number of New Gout Flares Per Patient During 24 Weeks
timeFrame: 24 weeks
measure: Time to First Intake of Rescue Medication
timeFrame: For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
measure: Percentage of Participants Who Took Rescue Medication
timeFrame: For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
measure: Amount of Rescue Medication Taken
timeFrame: For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
measure: Physician's Global Assessment of Response to Treatment
timeFrame: 72 hours post-dose and 24-weeks post-dose.
measure: Patient's Global Assessment of Response to Treatment
timeFrame: 72 hours post-dose and 24 weeks post-dose
measure: Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint
timeFrame: 72 hours post-dose and 24 weeks post-dose
measure: Physician's Assessment of Range of Motion of the Most Affected Joint
timeFrame: 72 hours post-dose and 24 weeks post-dose
measure: High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels
timeFrame: 72 hours after the first dose for the baseline flare and 72 hours post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
measure: Patient's Assessment of Gout Pain Intensity in the Most Affected Joint
timeFrame: 72 hours post-dose and 24 weeks post-dose
measure: Percentage of Patients With Maximum Severity of New Gout Flares as Severe or Extreme
timeFrame: From the onset of a new flare until re-dosing. First post-baseline new flare during 12 week core study and the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
measure: Time to First New Flare: Survival Analysis by Treatment Over 72 Weeks
timeFrame: From randomization to the end of the second extension period (72 weeks).
measure: Flare Rate Per Year
timeFrame: From randomization to the end of the second extension period (72 weeks).
measure: Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab
timeFrame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
measure: Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab
timeFrame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
measure: Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab
timeFrame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
measure: Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab
timeFrame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
measure: Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab
timeFrame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
measure: Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab
timeFrame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
measure: High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab
timeFrame: 24 hours, 72 hours, 7 days, 4, 8 and 12 weeks post-dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
measure: Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab
timeFrame: 24 hours, 72 hours, 7 days, 4, 8 and 12 weeks post-dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Foley
country: United States
facility: Novartis Investigative site
state: Alabama
city: Mobile
country: United States
facility: Horizon Research Group, Inc.
state: Alabama
city: Peoria
country: United States
facility: Sun Valley Arthritis Center, Ltd
state: Arizona
city: Tucson
country: United States
facility: Genova Clinical Research
state: Arizona
city: Little Rock
country: United States
facility: Little Rock Diagnostic Clinic
state: Arkansas
city: Burbank
country: United States
facility: Providence Research
state: California
city: Carlsbad
country: United States
facility: Diagnamics, Inc.
state: California
city: Fair Oaks
country: United States
facility: Med Investigations
state: California
city: Long Beach
country: United States
facility: Valerius Medical Group and Research Center of Long Branch
state: California
city: Norwalk
country: United States
facility: Lucita M. Cruz, M.D., Inc.
state: California
city: Orangevale
country: United States
facility: Sierra Clinical Research
state: California
city: Pomona
country: United States
facility: Chaparral Medical Grp, INC Clinical Research
state: California
city: Sacramento
country: United States
facility: River City Clinical Research
state: California
city: San Antonio
country: United States
facility: Arthritis Associates
state: California
city: San Diego
country: United States
facility: California Research Foundation
state: California
city: San Diego
country: United States
facility: Rochester clinical Research
state: California
city: San Diego
country: United States
facility: Ritchken and First MDs
state: California
city: San Marino
country: United States
facility: Huntington Medical Foundation
state: California
city: Santa Ana
country: United States
facility: Crest Clinical Trials
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Vista
country: United States
facility: Progressive Clinical Research
state: California
city: West Covina
country: United States
facility: Center for Clinical Trials of San Gabriel
state: California
city: Danbury
country: United States
facility: Clinical Res Ct of CT - Arthritis Associates of CT/NY, LLC
state: Connecticut
city: Clearwater
country: United States
facility: Innovative Research of West Florida
state: Florida
city: Jupiter
country: United States
facility: Health Awareness
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Research, LLC Pembroke Clinical Trials
state: Florida
city: Pinellas Park
country: United States
facility: DMI Healthcare Group, Inc.
state: Florida
city: Tampa
country: United States
facility: Tampa Medical Group, P.A.
state: Florida
city: Conyers
country: United States
facility: RST DAta Research
state: Georgia
city: Decatur
country: United States
facility: Q Clinical Research
state: Georgia
city: Rome
country: United States
facility: Harbin Clinic
state: Georgia
city: Boise
country: United States
facility: Sonora Clinical Research, LLC
state: Idaho
city: Boise
country: United States
facility: Northwest Clinical Trials
state: Idaho
city: Springfield
country: United States
facility: The Arthritis Center
state: Illinois
city: Evansville
country: United States
facility: Deaconess Clinic
state: Indiana
city: Overland Park
country: United States
facility: Pinnacle Medical Research
state: Kansas
city: Wichita
country: United States
facility: Wichita Clinic
state: Kansas
city: Baton Rouge
country: United States
facility: Dolby Research, LLC
state: Louisiana
city: Lafayette
country: United States
facility: Gulf Coast Research, LLC
state: Louisiana
city: Metairie
country: United States
facility: Clinical Trials Management
state: Louisiana
city: Monroe
country: United States
facility: Arthritis and Diabetes Clinic
state: Louisiana
city: Shreveport
country: United States
facility: Regional Research Specialists
state: Louisiana
city: Shreveport
country: United States
facility: The Family Doctors
state: Louisiana
city: Wheaton
country: United States
facility: Center for Rheumatology & Bone Research
state: Maryland
city: Waltham
country: United States
facility: MASS Research, LLC
state: Massachusetts
city: Clarkston
country: United States
facility: Clarkston Medical Group
state: Michigan
city: Flint
country: United States
facility: L Kage Healthcare Services
state: Michigan
city: Grand Rapids
country: United States
facility: West Michigan Rheumatology
state: Michigan
city: Lansing
country: United States
facility: *Private Practice*
state: Michigan
city: Troy
country: United States
facility: Oakland Medical Research Center
state: Michigan
city: Jackson
country: United States
facility: Arthritis Associates of Mississippi
state: Mississippi
city: Jackson
country: United States
facility: CRC of Jackson
state: Mississippi
city: Jackson
country: United States
facility: Phillips Medical Center
state: Mississippi
city: Missoula
country: United States
facility: Montana Medical Research
state: Montana
city: Omaha
country: United States
facility: Quality Clinical Research
state: Nebraska
city: Omaha
country: United States
facility: Heartland Clinical Research, Inc.
state: Nebraska
city: Henderson
country: United States
facility: Clinical Research Advantage, Inc
state: Nevada
city: Freehold
country: United States
facility: Arthritis and Osteoporosis Associates
state: New Jersey
city: New Brunswick
country: United States
facility: UMDNJ Robert Wood Johnson Medical School
state: New Jersey
city: Brooklyn
country: United States
facility: Arthritis and Osteoporosis Medical Association
state: New York
city: Roslyn
country: United States
facility: Andrew J. Porges, MD, PC
state: New York
city: Charlotte
country: United States
facility: Metrolina Medical Research
state: North Carolina
city: Charlotte
country: United States
facility: The Center For Nutrition and Preventive Medicine
state: North Carolina
city: Hickory
country: United States
facility: Unifour Medical Research Associates
state: North Carolina
city: Shelby
country: United States
facility: Jones Family Practice, PA
state: North Carolina
city: Columbus
country: United States
facility: Columbia Arthritis Center
state: Ohio
city: Dayton
country: United States
facility: STAT Research, Inc.
state: Ohio
city: Willoughby Hills
country: United States
facility: Ohio Clinical Research, LLC
state: Ohio
city: Youngstown
country: United States
facility: Humility of Mary Health Partners DBA St. Elizabeth Health Ce
state: Ohio
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma, PLLC
state: Oklahoma
city: Oklahoma City
country: United States
facility: Health Research Institute
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia VA medical Center
state: Pennsylvania
city: Bumberland
country: United States
facility: Partners in Clinical Research
state: Rhode Island
city: Charleston
country: United States
facility: Medical Research South
state: South Carolina
city: Charleston
country: United States
facility: Pharmacorp Clinical Trials, INC
state: South Carolina
city: Columbia
country: United States
facility: Tlm Medical Services Llc
state: South Carolina
city: Greenville
country: United States
facility: Palmetto Clinical Trial Services, LLC
state: South Carolina
city: Varnville
country: United States
facility: Community Research Partners, Inc.
state: South Carolina
city: Varnville
country: United States
facility: Community Research Partners, Inc.
state: South Carolina
city: Bristol
country: United States
facility: Tri-Cities Medical Research
state: Tennessee
city: Clarksville
country: United States
facility: Alpha Clinical Research
state: Tennessee
city: Jackson
country: United States
facility: The Jackson Clinic
state: Tennessee
city: Jackson
country: United States
facility: The Arthritis Clinic
state: Tennessee
city: Johnson City
country: United States
facility: MultiSpecialty Clinical Research
state: Tennessee
city: Austin
country: United States
facility: Lovelace Scientific Resource
state: Texas
city: Houston
country: United States
facility: Rheumatic Disease Clinical Research Center, Llc
state: Texas
city: Lake Jackson
country: United States
facility: R/D Clinical Research, Inc.
state: Texas
city: Leander
country: United States
facility: Leander Healthcare Center
state: Texas
city: Nassau Bay
country: United States
facility: Accurate Clinical Research
state: Texas
city: North Richard Hills
country: United States
facility: North Hills Family Practice
state: Texas
city: San Antonio
country: United States
facility: Arthritis Center South Texas
state: Texas
city: Danville
country: United States
facility: Novartis Investigative site
state: Virginia
city: Newport News
country: United States
facility: Health Research of Hampton Roads
state: Virginia
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: St-John's
country: Canada
facility: Novartis Investigative Site
state: Newfoundland and Labrador
city: Sainte Foy
country: Canada
facility: Novartis Investigative site
state: Quebec
city: Kaohsiung Hsien
country: China
facility: Novartis Investigative Site
state: Taiwan
city: Kaohsiung
country: China
facility: Novartis Investigative Site
state: Taiwan
city: Taichung
country: China
facility: Novartis Investigative Site
state: Taiwan
city: Taipei
country: China
facility: Novartis Investigative Site
state: Taiwan
city: Enschede
country: Netherlands
facility: Novartis Investigative Site
city: Leeuwarden
country: Netherlands
facility: Novartis Investigative site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Yaroslavl
country: Russian Federation
facility: Novartis Investigative Site
city: Yekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Chakraborty A, Van LM, Skerjanec A, Floch D, Klein UR, Krammer G, Sunkara G, Howard D. Pharmacokinetic and pharmacodynamic properties of canakinumab in patients with gouty arthritis. J Clin Pharmacol. 2013 Dec;53(12):1240-51. doi: 10.1002/jcph.162. Epub 2013 Sep 30.