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)
- Conditions
- Gout
- Interventions
- Registration Number
- NCT00819585
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 432
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Core study: Canakinumab 100 mg Placebo Matching Colchicine 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. Core study: Canakinumab 300 mg Placebo Matching Canakinumab 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. Core study: Canakinumab q4wk Placebo Matching Colchicine 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. Extension study: Group A Canakinumab Participants who were randomized to canakinumab in the core study and were treated with canakinumab for at least 1 flare in the extension study. Core study: Canakinumab 300 mg Placebo Matching Colchicine 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. Core study: Canakinumab 25 mg Placebo Matching Colchicine 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. Core study: Canakinumab 50 mg Placebo Matching Canakinumab 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. Core study: Canakinumab 100 mg Placebo Matching Canakinumab 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. Core study: Canakinumab 50 mg Placebo Matching Colchicine 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. Core study: Canakinumab 25 mg Placebo Matching Canakinumab 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. Core study: Canakinumab 200 mg Placebo Matching Canakinumab 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. Core study: Canakinumab 200 mg Placebo Matching Colchicine 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. Core study: Colchicine 0.5 mg Placebo Matching Canakinumab 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. Core study: Canakinumab 25 mg Canakinumab 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. Core study: Canakinumab 25 mg Allopurinol 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. Core study: Canakinumab 50 mg Canakinumab 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. Core study: Canakinumab 50 mg Allopurinol 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. Core study: Canakinumab 100 mg Canakinumab 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. Core study: Canakinumab 100 mg Allopurinol 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. Core study: Canakinumab 200 mg Canakinumab 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. Core study: Canakinumab 200 mg Allopurinol 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. Extension study: Group C Colchicine Patients who were randomized to colchicine in the core study and were treated with canakinumab for at least 1 flare in the extension study. Core study: Canakinumab 300 mg Canakinumab 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. Core study: Canakinumab 300 mg Allopurinol 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. Core study: Canakinumab q4wk Canakinumab 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. Core study: Canakinumab q4wk Allopurinol 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. Core study: Colchicine 0.5 mg Colchicine 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. Core study: Colchicine 0.5 mg Allopurinol 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. Extension study: Group B Canakinumab Patients who were randomized to canakinumab in the core study but did not receive treatment with canakinumab in the extension study. Extension study: Group C Canakinumab Patients who were randomized to colchicine in the core study and were treated with canakinumab for at least 1 flare in the extension study. Extension study: Group D Colchicine Patients who were randomized to colchicine in the core study but did not receive treatment with canakinumab in the extension study.
- Primary Outcome Measures
Name Time Method Core Study: Mean Number of Gout Flares Per Participant Baseline of the core study to Week 16 A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.
- Secondary Outcome Measures
Name Time Method Core Study: Percentage of Participants With Gout Flare at Different Time Points Days 2, 4, 6, and Weeks 2, 4, 6, 10, and 16 of the core study A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.
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 Extension Study: Amount of Rescue Medication Taken Baseline of the extension study until the end of the study (up to 24 weeks) The amount of naproxen and prednisolone taken after receiving treatment for each of the first 3 flares was recorded.
Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares Baseline of the core study to Week 16 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.
Extension Study: Participant's Assessment of Gout Pain on a 100 mm Visual Analog Scale During the First Flare Baseline of the extension study until 7 days after the onset of the first gout flare (up to 24 weeks) 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
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale Baseline of the extension study until the end of the study (up to 24 weeks) 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.
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale Baseline of the extension study until the end of the study (up to 24 weeks) 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.
Core Study: Percentage of Participants With at Least 1 Gout Flare Within 16 Weeks After Randomization Baseline of the core study to Week 16 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.
Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares Baseline of the core study to Week 16 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.
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale Days 15, 29, 57, 85, 113, and 141 of the core study 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.
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare Baseline of the extension study until the end of the study (up to 24 weeks) 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.
Trial Locations
- Locations (31)
Talbert Medical Group
🇺🇸Huntington Beach, California, United States
Health Awareness
🇺🇸Jupiter, Florida, United States
East-West Medical Research institute
🇺🇸Honolulu, Hawaii, United States
Pinnacle Medical Research
🇺🇸Overland Park, Kansas, United States
Cotton O'Neil Clinical Research Institute
🇺🇸Topeka, Kansas, United States
Shores Rheumatology
🇺🇸Saint Clair Shores, Michigan, United States
NM Clinical Research & Osteoporosis Ct.
🇺🇸Albuquerque, New Mexico, United States
Rochester clinical Research
🇺🇸Rochester, New York, United States
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Castlerock Clinical Research Consultants, LLC
🇺🇸Tulsa, Oklahoma, United States
Novartis Investigative Site
🇪🇸Barakaldo, Spain
Baskent University Medical Faculty
🇹🇷Ankara, Turkey
Cukurova University Medical Faculty
🇹🇷Balcali Adana, Turkey
Adnan Menderes University Medical Faculty
🇹🇷Aydin, Turkey
Pamukkale University medical Faculty
🇹🇷Denizli Kampus, Turkey
Gaziantep University Medical Faculty
🇹🇷Gaziantep, Turkey
Dokuz Eylul University Medical Faculty
🇹🇷Izmir, Turkey
Celal Bayar University Medical Faculty
🇹🇷Manisa, Turkey
Gables Medicentre
🇬🇧Coventry, United Kingdom
Flyde Coast Clinical Research Ltd
🇬🇧Lancashire, United Kingdom
Dolby Research, LLC
🇺🇸Baton Rouge, Louisiana, United States
Novartis Investigative site
🇨🇳Taipei, Taiwan
The Family Doctors
🇺🇸Shreveport, Louisiana, United States
Columbia Clinical Research
🇺🇸Columbia, South Carolina, United States
Fundación Cardiovascular de Colombia
🇨🇴Florida Blanca, Colombia
Upstate Pharmaceutical Research
🇺🇸Greenville, South Carolina, United States
MultiSpecialty Clinical Research
🇺🇸Johnson City, Tennessee, United States
San Diego Arthritis & Osteoporosis Medical clinic
🇺🇸San Diego, California, United States
Health Research of Oklahoma, PLLC
🇺🇸Oklahoma City, Oklahoma, United States
Heartland Clinical Research, Inc.
🇺🇸Omaha, Nebraska, United States
iMED Internal medicine, PA
🇺🇸San Antonio, Texas, United States