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Evaluating Efficacy of Canakinumab (ACZ885) in Prevention of Acute Flares in Chronic Gout Patients Initiating Allopurinol Therapy

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00819585
First received: January 8, 2009
Last updated: April 12, 2011
Last verified: April 2011
  Purpose

A 24-week, dose-ranging, multi-center, double-blind, double-dummy, active-controlled study to evaluate canakinumab (ACZ885) for prophylaxis of signs and symptoms of acute flares in chronic gout patients initiating allopurinol therapy


Condition Intervention Phase
Gout
Drug: Canakinumab 25 mg
Drug: Canakinumab 50 mg
Drug: Canakinumab 100 mg
Drug: Canakinumab 200 mg
Drug: Canakinumab 300 mg
Drug: Canakinumab repeated every 4 week (q4wk)
Drug: Colchicine
Drug: Allopurinol
Drug: Placebo Matching Canakinumab
Drug: Placebo Matching Colchicine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A 24-week, Dose-ranging, Multi-center, Double-blind, Double-dummy, Active-controlled Study to Evaluate Canakinumab (ACZ885) for Prophylaxis of Signs and Symptoms of Acute Flares in Chronic Gout Patients Initiating Allopurinol Therapy

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • The Mean Number of Gout Flares for Each Treatment Arm [ Time Frame: 16 weeks after randomization ] [ Designated as safety issue: No ]
    The primary efficacy variable was number of gout flares per participant per arm. Mean number of gout flares per treatment arm was derived from this primary variable. A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack. The target dose was defined as the minimum single dose that leads to at least the same expected efficacy as the expected efficacy of the comparator colchicine with respect to the mean number of gout flares. Four dose-response models (linear, linear in log-dose, logistic and emax) were chosen.


Secondary Outcome Measures:
  • The 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 ] [ Designated as safety issue: No ]
  • The Percentage of Participants With Gout Flares for Each Canakinumab Treatment Arm as Compared to Colchicine [ Time Frame: 16 weeks after randomization ] [ Designated as safety issue: No ]
    The percentage of participants experiencing at least one gout flare within 16 weeks after randomization. A gout flare was defined as an increase in patient-reported gout pain in the most affected joint during a gout attack. The start of a gout flare was defined as that day when the patient reported increased pain in the most affected joint for the first time in the patient diary. The end of a gout flare was defined as the patient's confirmation in the diary that the patient felt he/she had recovered from the gout flare or the acute gout pain had disappeared (whichever was first).

  • The Percentage of Participants With Gout Flare at Different Time Points for Each Canakinumab Treatment Arm as Compared to Colchicine [ Time Frame: 2 days, 4 days, 6 days, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 16 weeks ] [ Designated as safety issue: No ]
    A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack. The start of a gout flare was defined as that day when the patient reported increased pain in the most affected joint for the first time in the patient diary. The end of a gout flare was defined as the patient's confirmation in the diary that the patient felt he/she had recovered from the gout flare or the acute gout pain had disappeared (whichever was first).

  • Patient's Global Pain Intensity on a 0-100 mm Visual Analog Scale (VAS) up to Day 7 During All Gout Flares for Each Canakinumab Treatment Arm as Compared to Colchicine [ Time Frame: up to 16 weeks after randomization ] [ Designated as safety issue: No ]

    The pain intensity on a 0-100 mm VAS scale, ranging from no pain (0) to unbearable pain (100) in the affected joint (Scores on the 100-mm linear scale were measured to the nearest millimeter from the left)

    • on the day of onset of the gout flare and
    • in the morning of the 6 following days

  • Patient's Global Pain Intensity on 5-point Likert Scale up to Day 7 During All Gout Flares for Each Canakinumab Treatment Arm as Compared to Colchicine [ Time Frame: up to 16 weeks after randomization ] [ Designated as safety issue: No ]

    Participants were handed out a diary at baseline (Visit 2), Day 15 (Visit 3), Day 29 (Visit 4), Day 57 (Visit 5), Day 85 (Visit 6), Day 113 (Visit 7), and Day 141 (Visit 8) to record information on a daily basis during a gout flare. The patients were to score their current amount of acute gout pain in the joint on a 5-point Likert scale 1=None, 2=Mild, 3=Moderate, 4=Severe, 5=Extreme.

    • on the day of onset of the gout flare and
    • in the morning of the 6 following days

  • Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale for Each Canakinumab Treatment Arm as Compared to Colchicine [ Time Frame: At Day 15, Day 29, Day 57, Day 85, Day 113 and Day 141 ] [ Designated as safety issue: No ]
    To evaluate the efficacy of canakinumab as compared to colchicine with regards to the Physician's global assessment of response to therapy on a 5-point Likert scale up to 16 weeks after randomization. The study physician made a global assessment of the patient's response to treatment using a 5-point Likert scale: Very good, Good, Fair, Poor, Very poor. Physician's global assessment was performed at the visits like Day 15 (Visit 3), Day 29 (Visit 4), Day 57 (Visit 5), Day 85 (Visit 6), Day 113 (Visit 7), and Day 141 (Visit 8). The category 'Not assessed' combines the missing and 'not done'.


Enrollment: 432
Study Start Date: December 2008
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canakinumab 25 mg
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. 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 25 mg
25 mg subcutaneous injection once on day 1.
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: Canakinumab 50 mg
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. 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 50 mg
50 mg subcutaneous injection once on day 1.
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: Canakinumab 100 mg
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. 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 100 mg
100 mg subcutaneous injection once on day 1.
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: Canakinumab 200 mg
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. 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 200 mg
200 mg subcutaneous injection once on day 1.
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: Canakinumab 300 mg
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. 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 300 mg
300 mg subcutaneous injection once on day 1.
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: Canakinumab q4wk
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. 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 repeated every 4 week (q4wk)
50 mg subcutaneous injection (s.c) once on day 1 and day 29 followed by 25 mg s.c. once on Days 57, and 85.
Drug: Allopurinol
100- 300 mg orally once daily for 24 weeks.
Drug: Placebo Matching Colchicine
Capsule orally once daily for 16 weeks.
Active Comparator: 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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed written informed consent before any study procedure is performed.
  • History of at least 2 gout flares in the year prior to the Screening Visit (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

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00819585

  Show 89 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00819585     History of Changes
Other Study ID Numbers: CACZ885H2251, EudraCT : 2008-005876-28
Study First Received: January 8, 2009
Results First Received: February 28, 2011
Last Updated: April 12, 2011
Health Authority: Argentina: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Colombia: National Institutes of Health
Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Guatemala: Ministry of Health
Hungary: National Institute of Pharmacy
Portugal: National Pharmacy and Medicines Institute
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Pharmacological Committee, Ministry of Health
Singapore: Health Sciences Authority
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Novartis:
Gout
Chronic Gout
Gouty arthritis
Gout flares

Additional relevant MeSH terms:
Gout
Arthritis
Genetic Diseases, Inborn
Joint Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Musculoskeletal Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Rheumatic Diseases
Allopurinol
Antibodies, Monoclonal
Colchicine
Antimetabolites
Antimitotic Agents
Antineoplastic Agents
Antioxidants
Antirheumatic Agents
Enzyme Inhibitors
Free Radical Scavengers
Gout Suppressants
Immunologic Factors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 25, 2014