A Randomized, Controlled Study of ACZ885 (Canakinumab) on the Treatment and Prevention of Gout Flares in Patients With Frequent Flares for Whom NSAIDs and/or Colchicine Are Contraindicated, Not Tolerated or Ineffective Including a 12 Weeks Extension Study and a 1 Year Open-label Extension Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 226
- 试验地点
- 95
- 主要终点
- Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall)
研究概览
简要总结
The purpose of this study was to demonstrate that canakinumab given upon acute gout flares relieves the signs and symptoms and prevents recurrence of gout flares in patients with frequent flares of gout for whom non-steroidal anti-inflammatory drugs (NSAIDs) and/ or colchicine are contraindicated, not tolerated, or ineffective. The efficacy of canakinumab was compared to the corticosteroid triamcinolone acetonide.
The purpose of the first 12 week extension study was to collect additional safety, tolerability and efficacy data in patients who have completed the core study CACZ885H2357.
The purpose of the second one year open-label extension study was to confirm the long-term safety and tolerability of canakinumab in patients who had completed the first extension study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completion of the first extension study CACZ885H2357E
- •A patient was defined as completing the first extension study if they completed the study up to and including Visit 10).
排除标准
- •Continuation in this second extension study was considered inappropriate by the treating physician.
- •Other protocol-defined inclusion-exclusion criteria applied to the core and extension studies.
研究组 & 干预措施
Canakinumab 150 mg
Participants received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study.
In the second extension study participants were to receive open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year, for a total duration of 18 months.
干预措施: Canakinumab 150 mg (Drug)
Canakinumab 150 mg
Participants received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study.
In the second extension study participants were to receive open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year, for a total duration of 18 months.
干预措施: Placebo to triamcinolone acetonide (Drug)
Triamcinolone acetonide 40 mg
Participants received 1 intramuscular (im) injection of triamcinolone acetonide 40 mg and 1 subcutaneous (sc) injection of placebo to canakinumab on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study.
In the second extension study participants were to switch to open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year. Triamcinolone acetonide was not to be administered in the second extension study.
干预措施: Triamcinolone acetonide 40 mg (Drug)
Triamcinolone acetonide 40 mg
Participants received 1 intramuscular (im) injection of triamcinolone acetonide 40 mg and 1 subcutaneous (sc) injection of placebo to canakinumab on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study.
In the second extension study participants were to switch to open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year. Triamcinolone acetonide was not to be administered in the second extension study.
干预措施: Placebo to canakinumab (Drug)
结局指标
主要结局
Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall)
时间窗: 72 weeks
This was the primary endpoint of extension study 2. An adverse event was defined as any unfavorable and unintended diagnosis, symptom sign including an abnormal laboratory finding, syndrome or disease which either occurs during the study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS) at 72 Hours Post-dose
时间窗: 72 hours post-dose (randomization)
Patients scored their pain intensity in the joint most affected at Baseline on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100), at 72 hours post-dose. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The analysis of covariance (ANCOVA) analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates.
Time to First New Flare: Survival Analysis During the 12 Weeks of Study
时间窗: Baseline to 12 weeks
Kaplan-Meier estimates of time to first new flare and confidence intervals were determined. For patients with event, time to event = (date of event - date of first dose of study drug + 1). Patients met definition of new flare if they had: •Flare in joint, not a previously affected joint (at baseline or during study) •Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: • Increasing/renewed gout pain in an affected joint before flare has resolved completely.
Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks
时间窗: During 24 weeks overall
This was primary endpoint of extension study 1. Adverse event is defined as any unfavorable and unintended diagnosis, symptom sign including an abnormal laboratory finding, syndrome or disease which either occurs during the study, having been absent at baseline, or, if present at baseline, appears to worsen. A serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
次要结局
- Time to the First New Gout Flare During 24 Weeks(From randomization to the end of the first extension period (24 weeks).)
- Time to Complete Resolution of Pain; Survival Analysis(Baseline to 7 days post-dose (randomization))
- Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks of the Study(Baseline to Week 12)
- Time to at Least a 50% Reduction in Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS)(Baseline to 7 days post-dose (randomization))
- Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS)(6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose (randomization))
- Time to First Intake of Rescue Medication(For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).)
- SF 36 Physical Function Score at Week 12(Week 12)
- Pharmacokinetic Concentrations(12 weeks post-dose)
- Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS)(6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose for last post-baseline flare that occurred up until the end of the first extension study (24 weeks).)
- Mean Number of New Gout Flares Per Patient During 24 Weeks(24 weeks)
- Percentage of Participants Who Took Rescue Medication(For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).)
- Physician's Global Assessment of Response to Treatment(72 hours post-dose and 24-weeks post-dose.)
- Amount of Rescue Medication Taken(For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).)
- Patient's Global Assessment of Response to Treatment(72 hours post-dose and 24 weeks post-dose)
- Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint(72 hours post-dose and 24 weeks post-dose)
- Physician's Assessment of Range of Motion of the Most Affected Joint(72 hours post-dose and 24 weeks post-dose)
- High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels(72 hours after the first dose for the baseline flare and 72 hours post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).)
- Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab(72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.)
- Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab(24 hours, 72 hours, 7 days, 4, 8 and 12 weeks post-dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.)
- Patient's Assessment of Gout Pain Intensity in the Most Affected Joint(72 hours post-dose and 24 weeks post-dose)
- Percentage of Patients With Maximum Severity of New Gout Flares as Severe or Extreme(From the onset of a new flare until re-dosing. First post-baseline new flare during 12 week core study and the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).)
- Time to First New Flare: Survival Analysis by Treatment Over 72 Weeks(From randomization to the end of the second extension period (72 weeks).)
- Flare Rate Per Year(From randomization to the end of the second extension period (72 weeks).)
- Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab(72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.)
- Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab(72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.)
- Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab(72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.)
- Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab(72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.)
- Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab(72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.)
- High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab(24 hours, 72 hours, 7 days, 4, 8 and 12 weeks post-dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.)