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)

Phase 2CompletedNCT00819585

Novartis Pharmaceuticals432 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

432

Conditions

Gout

Interventions

CanakinumabDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (89)

Talbert Medical Group

Huntington Beach, California, United States

San Diego Arthritis & Osteoporosis Medical clinic

San Diego, 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

Outcomes

Primary Outcomes

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.

Time frame: Baseline of the core study to Week 16

Secondary Outcomes

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

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline of the extension study until the end of the study (up to 24 weeks)