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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)

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ClinicalTrials.gov Identifier: NCT00819585
Recruitment Status : Completed
First Posted : January 9, 2009
Results First Posted : May 6, 2011
Last Update Posted : July 17, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( 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.

Condition or disease Intervention/treatment Phase
Gout Drug: Canakinumab Drug: Colchicine Drug: Allopurinol Drug: Placebo Matching Canakinumab Drug: Placebo Matching Colchicine Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 432 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: 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
Study Start Date : December 2008
Actual Primary Completion Date : August 2010
Actual Study Completion Date : August 2010

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Gout
MedlinePlus related topics: Gout

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: Colchicine
0.5 mg capsule orally once daily for 16 weeks.

Drug: Allopurinol
100-300 mg orally once daily for 24 weeks.

Drug: Placebo Matching Canakinumab
Subcutaneous injection.

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.




Primary Outcome Measures :
  1. Core Study: Mean Number of Gout Flares Per Participant [ Time Frame: 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 :
  1. Core Study: Mean Number of Gout Flares for the Repeat Dose Regimen of Canakinumab as Compared to the Single Doses of Canakinumab [ Time Frame: up to 16 weeks after randomization ]
  2. Core Study: Percentage of Participants With at Least 1 Gout Flare Within 16 Weeks After Randomization [ Time Frame: 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.

  3. Core Study: Percentage of Participants With Gout Flare at Different Time Points [ Time Frame: 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.

  4. Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares [ Time Frame: 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.

  5. Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares [ Time Frame: 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.

  6. Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale [ Time Frame: 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.

  7. Extension Study: Participant's Assessment of Gout Pain on a 100 mm Visual Analog Scale During the First Flare [ Time Frame: 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

  8. Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale [ Time Frame: 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.

  9. Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale [ Time Frame: 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.

  10. Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare [ Time Frame: 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.

  11. Extension Study: Amount of Rescue Medication Taken [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00819585


  Show 89 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00819585     History of Changes
Other Study ID Numbers: CACZ885H2251
EudraCT : 2008-005876-28
First Posted: January 9, 2009    Key Record Dates
Results First Posted: May 6, 2011
Last Update Posted: July 17, 2018
Last Verified: June 2018
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Gout
Chronic gout
Gouty arthritis
Gout flares
Additional relevant MeSH terms:
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Gout
Gout Suppressants
Arthritis
Joint Diseases
Musculoskeletal Diseases
Crystal Arthropathies
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Colchicine
Allopurinol
Antibodies, Monoclonal
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Antirheumatic Agents
Free Radical Scavengers
Antioxidants
Protective Agents
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents
Immunologic Factors