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.
β-RELIEVED-II
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
3 other identifiers
interventional
226
5 countries
108
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Mar 2010
108 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2010
CompletedFirst Submitted
Initial submission to the registry
March 2, 2010
CompletedFirst Posted
Study publicly available on registry
March 3, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2011
CompletedResults Posted
Study results publicly available
December 26, 2011
CompletedJanuary 30, 2014
April 1, 2013
8 months
March 2, 2010
August 30, 2011
December 24, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Time to First New Flare: Survival Analysis During the 12 Weeks of Study
Kaplan-Meier estimates of time to first new flare and confidence intervals were determined. For patients with event, time to event = (date of event - date of first dose of study drug + 1). Patients met definition of new flare if they had: •Flare in joint, not a previously affected joint (at baseline or during study) •Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: • Increasing/renewed gout pain in an affected joint before flare has resolved completely.
Baseline to 12 weeks
Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS) at 72 Hours Post-dose
Patients scored their pain intensity in the joint most affected at Baseline on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100), at 72 hours post-dose. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The analysis of covariance (ANCOVA) analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates.
72 hours post-dose (randomization)
Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks
This was primary endpoint of extension study 1. Adverse event is defined as any unfavorable and unintended diagnosis, symptom sign including an abnormal laboratory finding, syndrome or disease which either occurs during the study, having been absent at baseline, or, if present at baseline, appears to worsen. A serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
During 24 weeks overall
Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall)
This was the primary endpoint of extension study 2. An adverse event was defined as any unfavorable and unintended diagnosis, symptom sign including an abnormal laboratory finding, syndrome or disease which either occurs during the study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
72 weeks
Secondary Outcomes (29)
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)
Baseline to 7 days post-dose (randomization)
Time to Complete Resolution of Pain; Survival Analysis
Baseline to 7 days post-dose (randomization)
SF 36 Physical Function Score at Week 12
Week 12
Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks of the Study
Baseline to Week 12
Pharmacokinetic Concentrations
12 weeks post-dose
- +24 more secondary outcomes
Study Arms (2)
Canakinumab 150 mg
EXPERIMENTALParticipants received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study. In the second extension study participants were to receive open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year, for a total duration of 18 months.
Triamcinolone acetonide 40 mg
ACTIVE COMPARATORParticipants received 1 intramuscular (im) injection of triamcinolone acetonide 40 mg and 1 subcutaneous (sc) injection of placebo to canakinumab on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study. In the second extension study participants were to switch to open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year. Triamcinolone acetonide was not to be administered in the second extension study.
Interventions
Canakinumab 150 mg was supplied in 6 mL glass vials each containing nominally 150 mg canakinumab (plus 20% overfill).
Triamcinolone acetonide 40 mg was supplied as a suspension.
Placebo to canakinumab was supplied in 6 mL glass vials containing placebo powder as a lyophilized cake.
Placebo triamcinolone acetonide was supplied as a lipid emulsion similar in appearance to triamcinolone acetonide.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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:
- \- 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.
- \- Continuation in this extension study was considered inappropriate by the treating physician.
- Extension Study 2:
- 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).
- Continuation in this second extension study was considered inappropriate by the treating physician.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (108)
Pinnacle Research Group, LLC
Anniston, Alabama, 36207, United States
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Novartis Investigative site
Foley, Alabama, 36535, United States
Horizon Research Group, Inc.
Mobile, Alabama, 36608, United States
Sun Valley Arthritis Center, Ltd
Peoria, Arizona, 85381, United States
Genova Clinical Research
Tucson, Arizona, 85741, United States
Little Rock Diagnostic Clinic
Little Rock, Arkansas, 72205, United States
Providence Research
Burbank, California, 91505, United States
Diagnamics, Inc.
Carlsbad, California, 92008, United States
Med Investigations
Fair Oaks, California, 95628, United States
Valerius Medical Group and Research Center of Long Branch
Long Beach, California, 90806, United States
Lucita M. Cruz, M.D., Inc.
Norwalk, California, 90650, United States
Sierra Clinical Research
Orangevale, California, 95662, United States
Chaparral Medical Grp, INC Clinical Research
Pomona, California, 91767, United States
River City Clinical Research
Sacramento, California, 95816, United States
Arthritis Associates
San Antonio, California, 782209, United States
California Research Foundation
San Diego, California, 92103, United States
Rochester clinical Research
San Diego, California, 92108, United States
Ritchken and First MDs
San Diego, California, 92117, United States
Huntington Medical Foundation
San Marino, California, 91108, United States
Crest Clinical Trials
Santa Ana, California, 92701, United States
Orange County Research Center
Tustin, California, 92780, United States
Progressive Clinical Research
Vista, California, 92803, United States
Center for Clinical Trials of San Gabriel
West Covina, California, 91790, United States
Clinical Res Ct of CT - Arthritis Associates of CT/NY, LLC
Danbury, Connecticut, 06810, United States
Innovative Research of West Florida
Clearwater, Florida, 33756, United States
Health Awareness
Jupiter, Florida, 33458, United States
Pines Research, LLC Pembroke Clinical Trials
Pembroke Pines, Florida, 33028, United States
DMI Healthcare Group, Inc.
Pinellas Park, Florida, 33782, United States
Tampa Medical Group, P.A.
Tampa, Florida, 33614, United States
RST DAta Research
Conyers, Georgia, 30012, United States
Q Clinical Research
Decatur, Georgia, 30035, United States
Harbin Clinic
Rome, Georgia, 30165, United States
Sonora Clinical Research, LLC
Boise, Idaho, 83702, United States
Northwest Clinical Trials
Boise, Idaho, 83704, United States
The Arthritis Center
Springfield, Illinois, 62704, United States
Deaconess Clinic
Evansville, Indiana, 47713, United States
Pinnacle Medical Research
Overland Park, Kansas, 66215, United States
Wichita Clinic
Wichita, Kansas, 67208, United States
Dolby Research, LLC
Baton Rouge, Louisiana, 70809, United States
Gulf Coast Research, LLC
Lafayette, Louisiana, 70508, United States
Clinical Trials Management
Metairie, Louisiana, 70006, United States
Arthritis and Diabetes Clinic
Monroe, Louisiana, 71203, United States
Regional Research Specialists
Shreveport, Louisiana, 71106, United States
The Family Doctors
Shreveport, Louisiana, 71115, United States
Center for Rheumatology & Bone Research
Wheaton, Maryland, 20902, United States
MASS Research, LLC
Waltham, Massachusetts, 02453, United States
Clarkston Medical Group
Clarkston, Michigan, 48346, United States
L Kage Healthcare Services
Flint, Michigan, 48532, United States
West Michigan Rheumatology
Grand Rapids, Michigan, 49546, United States
*Private Practice*
Lansing, Michigan, 48910, United States
Oakland Medical Research Center
Troy, Michigan, 48085, United States
Arthritis Associates of Mississippi
Jackson, Mississippi, 39202, United States
CRC of Jackson
Jackson, Mississippi, 39202, United States
Phillips Medical Center
Jackson, Mississippi, 39209, United States
Montana Medical Research
Missoula, Montana, 59808, United States
Quality Clinical Research
Omaha, Nebraska, 68114, United States
Heartland Clinical Research, Inc.
Omaha, Nebraska, 68134, United States
Clinical Research Advantage, Inc
Henderson, Nevada, 89014, United States
Arthritis and Osteoporosis Associates
Freehold, New Jersey, 07728, United States
UMDNJ Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08903, United States
Arthritis and Osteoporosis Medical Association
Brooklyn, New York, 11201, United States
Andrew J. Porges, MD, PC
Roslyn, New York, 11576, United States
Metrolina Medical Research
Charlotte, North Carolina, 28209, United States
The Center For Nutrition and Preventive Medicine
Charlotte, North Carolina, 28277, United States
Unifour Medical Research Associates
Hickory, North Carolina, 28601, United States
Jones Family Practice, PA
Shelby, North Carolina, 28150, United States
Columbia Arthritis Center
Columbus, Ohio, 43215, United States
STAT Research, Inc.
Dayton, Ohio, 45417, United States
Ohio Clinical Research, LLC
Willoughby Hills, Ohio, 44094, United States
Humility of Mary Health Partners DBA St. Elizabeth Health Ce
Youngstown, Ohio, 44501, United States
Health Research of Oklahoma, PLLC
Oklahoma City, Oklahoma, 73103, United States
Health Research Institute
Oklahoma City, Oklahoma, 73109, United States
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635, United States
Philadelphia VA medical Center
Philadelphia, Pennsylvania, 19104, United States
Partners in Clinical Research
Bumberland, Rhode Island, 02864, United States
Medical Research South
Charleston, South Carolina, 29407, United States
Pharmacorp Clinical Trials, INC
Charleston, South Carolina, 29412, United States
Tlm Medical Services Llc
Columbia, South Carolina, 29204, United States
Palmetto Clinical Trial Services, LLC
Greenville, South Carolina, 29601, United States
Community Research Partners, Inc.
Varnville, South Carolina, 29924, United States
Community Research Partners, Inc.
Varnville, South Carolina, 29944, United States
Tri-Cities Medical Research
Bristol, Tennessee, 37620, United States
Alpha Clinical Research
Clarksville, Tennessee, 37403, United States
The Jackson Clinic
Jackson, Tennessee, 38301, United States
The Arthritis Clinic
Jackson, Tennessee, 38305, United States
MultiSpecialty Clinical Research
Johnson City, Tennessee, 37601, United States
Lovelace Scientific Resource
Austin, Texas, 78758, United States
Rheumatic Disease Clinical Research Center, Llc
Houston, Texas, 77004, United States
R/D Clinical Research, Inc.
Lake Jackson, Texas, 77566, United States
Leander Healthcare Center
Leander, Texas, 78641, United States
Accurate Clinical Research
Nassau Bay, Texas, 77058, United States
North Hills Family Practice
North Richard Hills, Texas, 76180, United States
Arthritis Center South Texas
San Antonio, Texas, 78232, United States
Novartis Investigative site
Danville, Virginia, 24541, United States
Health Research of Hampton Roads
Newport News, Virginia, 23606, United States
Novartis Investigative Site
Vancouver, British Columbia, Canada
Novartis Investigative Site
St. John's, Newfoundland and Labrador, Canada
Novartis Investigative site
Sainte-Foy, Quebec, Canada
Novartis Investigative Site
Kaohsiung Hsien, Taiwan, China
Novartis Investigative Site
Kaohsiung, Taiwan, China
Novartis Investigative Site
Taichung, Taiwan, China
Novartis Investigative Site
Taipei, Taiwan, China
Novartis Investigative Site
Enschede, Netherlands
Novartis Investigative site
Leeuwarden, Netherlands
Novartis Investigative Site
Moscow, Russia
Novartis Investigative Site
Yaroslavl, Russia
Novartis Investigative Site
Yekaterinburg, Russia
Related Publications (1)
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.
PMID: 24122883DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 2, 2010
First Posted
March 3, 2010
Study Start
March 1, 2010
Primary Completion
November 1, 2010
Study Completion
October 1, 2011
Last Updated
January 30, 2014
Results First Posted
December 26, 2011
Record last verified: 2013-04