A Study of the Efficacy of Canakinumab in Prevention of Acute Flares in Chronic Gout Patients Initiating Allopurinol Therapy (Core Study) and a Long-term Study of the Efficacy and Safety of Canakinumab in Patients With Gout (Extension Study)

A 24-week, Dose-ranging, Multicenter, Double-blind, Double-dummy, Active-controlled Core Study to Evaluate Canakinumab for Prophylaxis of Signs and Symptoms of Acute Flares in Chronic Gout Patients Initiating Allopurinol Therapy and a 24-week Open-label, Multicenter Extension Study to Assess Safety, Tolerability and Efficacy of Canakinumab in Patients With Gout Who Are Given Canakinumab at the Time of Gout Flare

The 24-week, dose-ranging, multi-center, double-blind, double-dummy, active-controlled core study investigated the prophylactic effect of canakinumab on the signs and symptoms of acute flares in chronic gout patients initiating allopurinol therapy. The core study was followed by a 24-week open-label, multicenter extension study to assess the safety, tolerability, and efficacy of canakinumab in patients with gout who were given canakinumab at the time of gout flare.

Study Overview

• Status: Completed
• Conditions: Gout
• Intervention / Treatment: Drug: Canakinumab; Drug: Allopurinol; Drug: Placebo Matching Canakinumab; Drug: Placebo Matching Colchicine; Drug: Colchicine

• Study Type: Interventional
• Enrollment (Actual): 432
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Novartis Investigative Site
  • Cordoba, Argentina
    • Novartis Investigative Site
  • Rosario, Argentina
    • Novartis Investigative Site
• Belgium
  • Gozée, Belgium
    • Novartis Investigative Site
  • Oostham, Belgium
    • Novartis Investigative Site
• Colombia
  • Bacaramanga, Colombia
    • Novartis Investigative Site
  • Barranquilla, Colombia
    • Novartis Investigative Site
  • Bogota, Colombia
    • Novartis Investigative Site
  • Florida Blanca, Colombia
    • Fundacion Cardiovascular de Colombia
• Czechia
  • Havirov, Czechia
    • Novartis Investigative Site
  • Ostrava, Czechia
    • Novartis Investigative Site
  • Pardubice, Czechia
    • Novartis Investigative Site
  • Uherske Hradiste, Czechia
    • Novartis Investigative Site
  • Zlin, Czechia
    • Novartis Investigative Site
• Germany
  • Bautzen, Germany
    • Novartis Investigative Site
  • Chemnitz, Germany
    • Novartis Investigative Site
  • Dresden, Germany
    • Novartis Investigative Site
  • Frankfurt, Germany
    • Novartis Investigative Site
  • Georgensgmuend, Germany
    • Novartis Investigative Site
  • Goettingen, Germany
    • Novartis Investigative Site
  • Hamburg, Germany
    • Novartis Investigative Site
  • Magdeburg, Germany
    • Novartis Investigative Site
  • Messkirch, Germany
    • Novartis Investigative Site
  • Muenchen, Germany
    • Novartis Investigative Site
  • Riedlhuette, Germany
    • Novartis Investigative Site
  • Schwabach, Germany
    • Novartis Investigative Site
• Guatemala
  • Guatemala City, Guatemala
    • Novartis Investigative Site
• Hungary
  • Debrecen, Hungary
    • Novartis Investigative Site
  • Eger, Hungary
    • Novartis Investigative Site
  • Kistarcsa, Hungary
    • Novartis Investigative Site
  • Zalaegerszeg, Hungary
    • Novartis Investigative Site
• Poland
  • Poznan, Poland
    • Novartis Investigative Site
  • Wroclaw, Poland
    • Novartis Investigative Site
• Portugal
  • Coimbra, Portugal
    • Novartis Investigative Site
  • Lisboa, Portugal
    • Novartis Investigative Site
  • Ponte de Lima, Portugal
    • Novartis Investigative Site
• Russian Federation
  • Chelyabinsk, Russian Federation
    • Novartis Investigative Site
  • Ekaterinburg, Russian Federation
    • Novartis Investigative Site
  • Moscow, Russian Federation
    • Novartis Investigative Site
  • Petrozavodsk, Russian Federation
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore
    • Novartis Investigative Site
• Slovakia
  • Banska Bystrica, Slovakia
    • Novartis Investigative Site
  • Bratislava, Slovakia
    • Novartis Investigative Site
  • Kosice, Slovakia
    • Novartis Investigative Site
  • Nove Zamky, Slovakia
    • Novartis Investigative Site
  • Piestany, Slovakia
    • Novartis Investigative Site
  • Povazska Bystrica, Slovakia
    • Novartis Investigative Site
  • Trebisova, Slovakia
    • Novartis Investigative Site
• South Africa
  • Cape Town, South Africa
    • Novartis Investigative Site
  • Panorama, South Africa
    • Novartis Investigative Site
  • Port Elizabeth, South Africa
    • Novartis Investigative Site
• Spain
  • Barakaldo, Spain
    • Novartis Investigative Site
  • Madrid, Spain
    • Novartis Investigative Site
  • Merida, Spain
    • Novartis Investigative Site
  • Valencia, Spain
    • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan
    • Novartis Investigative Site
  • Taichung, Taiwan
    • Novartis Investigative Site
  • Taipei, Taiwan
    • Novartis Investigative Site
• Turkey
  • Adana, Turkey
    • Baskent University Medical faculty
  • Ankara, Turkey
    • Baskent University Medical faculty
  • Aydin, Turkey
    • Adnan Menderes University Medical Faculty
  • Balcali Adana, Turkey
    • Cukurova University Medical Faculty
  • Denizli Kampus, Turkey
    • Pamukkale University Medical Faculty
  • Gaziantep, Turkey
    • Gaziantep University Medical Faculty
  • Izmir, Turkey
    • Dokuz Eylul University Medical Faculty
  • Manisa, Turkey
    • Celal Bayar University Medical Faculty
• United Kingdom
  • Coventry, United Kingdom
    • Gables Medicentre
  • Lancashire, United Kingdom
    • Flyde Coast Clinical Research Ltd
• United States
  • California
    • Huntington Beach, California, United States, 92646
      • Talbert Medical Group
    • San Diego, California, United States
      • San Diego Arthritis & Osteoporosis Medical Clinic
  • Florida
    • Jupiter, Florida, United States, 33458
      • Health Awareness
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Kansas
    • Overland Park, Kansas, United States, 66215
      • Pinnacle Medical Research
    • Topeka, Kansas, United States
      • Cotton O'Neil Clinical Research Institute
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Dolby Research, LLC
    • Shreveport, Louisiana, United States, 71115
      • The Family Doctors
  • Michigan
    • Saint Clair Shores, Michigan, United States, 48081
      • Shores Rheumatology
  • Nebraska
    • Omaha, Nebraska, United States
      • Heartland Clinical Research, Inc.
  • New Mexico
    • Albuquerque, New Mexico, United States
      • NM Clinical Research & Osteoporosis Ct.
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma, PLLC
    • Tulsa, Oklahoma, United States, 74136
      • Castlerock Clinical Research Consultants, Llc
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Columbia Clinical Research
    • Greenville, South Carolina, United States, 29615
      • Upstate Pharmaceutical Research
  • Tennessee
    • Johnson City, Tennessee, United States
      • MultiSpecialty Clinical Research
  • Texas
    • San Antonio, Texas, United States, 78228
      • iMED Internal medicine, PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Core study

Inclusion Criteria:

• Signed written informed consent before any study procedure is performed.
• History of at least 2 gout flares in the year prior to Screening (Visit 1, based on patient history), thus, candidates for initiating uric acid lowering therapy.
• Confirmed diagnosis of gout meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of arthritis of primary gout.
• Body Mass Index (BMI) ≤ 40 kg/m^2.
• Willingness to initiate allopurinol therapy as urate lowering agent for their gout therapy or having initiated allopurinol therapy within ≤ 1 month before Screening (Visit 1) or willing to re-initiate allopurinol therapy if this was stopped > 2 months before Screening (Visit 1) for reasons different to toxicity/ intolerance or lack of efficacy.

Exclusion Criteria:

• Acute gout flare within 2 weeks of Screening (Visit 1) and during the Screening period.
• History of allergy or contraindication to colchicine or allopurinol.
• History of intolerance to allopurinol or to oral colchicine in appropriate dose for prophylactic use.
• History of bone marrow suppression.
• Absolute or relative contraindication to both naproxen and oral prednisolone/ prednisone.

Extension study

Inclusion criteria:

• Patients who completed the core study. A patient is defined as completing the core study if he/she completed the study up to and including the last visit (Visit 9).
• Patients who have signed a written informed consent before any trial procedure is performed.

Exclusion Criteria:

• Patients for whom continuation in the extension study is not considered appropriate by the treating physician.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive pregnancy test (serum or urine).

Other protocol-defined inclusion/exclusion criteria applied to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Core study: Canakinumab 25 mg; Canakinumab 25 mg subcutaneously (sc) once at Day 1, placebo sc at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.	Drug: Canakinumab; Canakinumab was supplied in glass vials as a lyophilized powder.; Drug: Allopurinol; 100-300 mg orally once daily for 24 weeks.; Drug: Placebo Matching Canakinumab; Subcutaneous injection.; Drug: Placebo Matching Colchicine; Capsule orally once daily for 16 weeks.
Experimental: Core study: Canakinumab 50 mg; Canakinumab 50 mg sc once at Day 1, placebo sc at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.	Drug: Canakinumab; Canakinumab was supplied in glass vials as a lyophilized powder.; Drug: Allopurinol; 100-300 mg orally once daily for 24 weeks.; Drug: Placebo Matching Canakinumab; Subcutaneous injection.; Drug: Placebo Matching Colchicine; Capsule orally once daily for 16 weeks.
Experimental: Core study: Canakinumab 100 mg; Canakinumab 100 mg sc once at Day 1, placebo sc at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.	Drug: Canakinumab; Canakinumab was supplied in glass vials as a lyophilized powder.; Drug: Allopurinol; 100-300 mg orally once daily for 24 weeks.; Drug: Placebo Matching Canakinumab; Subcutaneous injection.; Drug: Placebo Matching Colchicine; Capsule orally once daily for 16 weeks.
Experimental: Core study: Canakinumab 200 mg; Canakinumab 100 mg sc once at Day 1, placebo sc at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.	Drug: Canakinumab; Canakinumab was supplied in glass vials as a lyophilized powder.; Drug: Allopurinol; 100-300 mg orally once daily for 24 weeks.; Drug: Placebo Matching Canakinumab; Subcutaneous injection.; Drug: Placebo Matching Colchicine; Capsule orally once daily for 16 weeks.
Experimental: Core study: Canakinumab 300 mg; Canakinumab 300 mg sc once at Day 1, placebo sc at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.	Drug: Canakinumab; Canakinumab was supplied in glass vials as a lyophilized powder.; Drug: Allopurinol; 100-300 mg orally once daily for 24 weeks.; Drug: Placebo Matching Canakinumab; Subcutaneous injection.; Drug: Placebo Matching Colchicine; Capsule orally once daily for 16 weeks.
Experimental: Core study: Canakinumab q4wk; Canakinumab 50 mg sc at Days 1, and 29 followed by canakinumab 25 mg sc on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.	Drug: Canakinumab; Canakinumab was supplied in glass vials as a lyophilized powder.; Drug: Allopurinol; 100-300 mg orally once daily for 24 weeks.; Drug: Placebo Matching Colchicine; Capsule orally once daily for 16 weeks.
Active Comparator: Core study: Colchicine 0.5 mg; Colchicine 0.5 mg capsule orally once daily throughout the whole treatment phase of 16 weeks plus placebo matching canakinumab s.c. at Days 1, 29, 57, and 85. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.	Drug: Allopurinol; 100-300 mg orally once daily for 24 weeks.; Drug: Placebo Matching Canakinumab; Subcutaneous injection.; Drug: Colchicine; 0.5 mg capsule orally once daily for 16 weeks.
Experimental: Extension study: Group A; Participants who were randomized to canakinumab in the core study and were treated with canakinumab for at least 1 flare in the extension study.	Drug: Canakinumab; Canakinumab was supplied in glass vials as a lyophilized powder.
Experimental: Extension study: Group B; Patients who were randomized to canakinumab in the core study but did not receive treatment with canakinumab in the extension study.	Drug: Canakinumab; Canakinumab was supplied in glass vials as a lyophilized powder.
Experimental: Extension study: Group C; Patients who were randomized to colchicine in the core study and were treated with canakinumab for at least 1 flare in the extension study.	Drug: Canakinumab; Canakinumab was supplied in glass vials as a lyophilized powder.; Drug: Colchicine; 0.5 mg capsule orally once daily for 16 weeks.
Experimental: Extension study: Group D; Patients who were randomized to colchicine in the core study but did not receive treatment with canakinumab in the extension study.	Drug: Colchicine; 0.5 mg capsule orally once daily for 16 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Study: Mean Number of Gout Flares Per Participant	A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.	Baseline of the core study to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Study: Mean Number of Gout Flares for the Repeat Dose Regimen of Canakinumab as Compared to the Single Doses of Canakinumab		up to 16 weeks after randomization
Core Study: Percentage of Participants With at Least 1 Gout Flare Within 16 Weeks After Randomization	The percentage of participants experiencing at least 1 gout flare within 16 weeks after randomization. A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.	Baseline of the core study to Week 16
Core Study: Percentage of Participants With Gout Flare at Different Time Points	A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.	Days 2, 4, 6, and Weeks 2, 4, 6, 10, and 16 of the core study
Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares	Participants rated the intensity of pain in the most affected joint on a 0-100 mm visual analog scale, which ranged from no pain (left end, 0) to unbearable pain (right end, 100). Participants assessed pain intensity on the day of onset of the gout flare and in the morning of the 6 following days.	Baseline of the core study to Week 16
Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares	Participants assessed the intensity of pain in the most affected joint on a 5-point Likert scale, which ranged from 1 to 5 (1=None, 2=Mild, 3=Moderate, 4=Severe, 5=Extreme). Participants assessed pain intensity on the day of onset of the gout flare and in the morning of the 6 following days.	Baseline of the core study to Week 16
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale	The study physician made a global assessment of the participant's response to treatment on a 5-point Likert scale (Very good, Good, Fair, Poor, Very poor) at Days 15, 29, 57, 85, 113, and 141. The category 'Not assessed' includes missing data and 'not done'. The number of participants in each of the 5 categories of the Likert scale are reported.	Days 15, 29, 57, 85, 113, and 141 of the core study
Extension Study: Participant's Assessment of Gout Pain on a 100 mm Visual Analog Scale During the First Flare	Participant's rated the intensity of pain in the most affected joint during the first flare on a 0-100 mm visual analog scale, which ranged from no pain (left end, 0) to unbearable pain (right end, 100). Assessments were made pre-dose and 24 hours, 3 days, 4 days, and an average of 5-7 days post-dose	Baseline of the extension study until 7 days after the onset of the first gout flare (up to 24 weeks)
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale	Study participants made a global assessment of their response to treatment on a 5-point Likert scale (Excellent, Good, Acceptable, Slight, Poor) at the control visit 7±2 days following each of their first 3 flares. The number of participants in each of the 5 categories of the Likert scale are reported.	Baseline of the extension study until the end of the study (up to 24 weeks)
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale	The study physician made a global assessment of the participant's response to treatment on a 5-point Likert scale (Very good, Good, Fair, Poor, Very poor) at the control visit 7±2 days following each of the first 3 flares. The category 'Not assessed' includes missing data and 'not done'. The number of participants in each of the 5 categories of the Likert scale are reported.	Baseline of the extension study until the end of the study (up to 24 weeks)
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare	Tenderness was rated on a 0-3 point scale: 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 most affected joint. Swelling was rated on a 0-3 point scale: 0="no swelling", 1="palpable", 2="visible", and 3=bulging beyond the joint margins". Erythema was rated as present, absent, or not assessable. Assessments were performed at the flare and control visits.	Baseline of the extension study until the end of the study (up to 24 weeks)
Extension Study: Amount of Rescue Medication Taken	The amount of naproxen and prednisolone taken after receiving treatment for each of the first 3 flares was recorded.	Baseline of the extension study until the end of the study (up to 24 weeks)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: January 8, 2009
• First Submitted That Met QC Criteria: January 8, 2009
• First Posted (Estimate): January 9, 2009

Study Record Updates

• Last Update Posted (Actual): July 17, 2018
• Last Update Submitted That Met QC Criteria: June 19, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Gout; Gout flares; Gouty arthritis; Chronic gout
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Gout; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Antibodies, Monoclonal; Colchicine; Allopurinol
• Other Study ID Numbers: CACZ885H2251; EudraCT : 2008-005876-28