A 12 Weeks Randomized, Controlled Core 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-week Double-blind Extension Study and an Open-label 48 Week Extension Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 230
- 试验地点
- 2
- 主要终点
- Time to First New Flare
研究概览
简要总结
The purpose of the 12-week core 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 CACZ885H2356.
The purpose of the second 48 week open-label extension study was to collect additional long-term safety and tolerability data in patients who have completed the first extension study CACZ885H2356E1.
详细描述
Masking:
Core: Double Blind (Subject, Investigator) Extension 1: Double Blind (Subject, Investigator) Extension 2: Open-label, terminated
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Canakinumab 150 mg
Patients received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Patients could receive re-dose of study drug on demand upon occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after previous dose. Patients completing 12 weeks core study were allowed to continue treatment in another 12-week extension for any new gout flare on demand with same treatment as assigned in core study.
After completing the first extension, patients were offered to enter second extension study, whereby all patients were treated open-label "on demand" with canakinumab 150 mg sc upon new flare for 1 year for a total duration of 18 months following randomization in core study. Patients completing first 12 weeks extension study were allowed to continue to be treated in another single-arm, open-label 48 weeks extension when all patients from both treatment arms received canakinumab on demand
干预措施: Canakinumab 150 mg (Drug)
Canakinumab 150 mg
Patients received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Patients could receive re-dose of study drug on demand upon occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after previous dose. Patients completing 12 weeks core study were allowed to continue treatment in another 12-week extension for any new gout flare on demand with same treatment as assigned in core study.
After completing the first extension, patients were offered to enter second extension study, whereby all patients were treated open-label "on demand" with canakinumab 150 mg sc upon new flare for 1 year for a total duration of 18 months following randomization in core study. Patients completing first 12 weeks extension study were allowed to continue to be treated in another single-arm, open-label 48 weeks extension when all patients from both treatment arms received canakinumab on demand
干预措施: Placebo to triamcinolone acetonide (Drug)
Triamcinolone acetonide 40 mg
Patients received 1 intramuscular (im) injection of triamcinolone acetonide 40 mg and 1 subcutaneous (sc) injection of placebo to canakinumab on Day 1. Patients 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. Patients completing the 12 weeks core study were allowed to continue to be treated in another 12 weeks extension study for any new gout flare on demand with the same treatment as assigned in the core study.
Patients under this arm who agreed to continue to 2nd extension period of 12 months, were switched to canakinumab 150 mg sc for any new gout flare during this period Triamcinolone acetonide was not to be administered in the 48-week session.
干预措施: Triamcinolone acetonide 40 mg (Drug)
Triamcinolone acetonide 40 mg
Patients received 1 intramuscular (im) injection of triamcinolone acetonide 40 mg and 1 subcutaneous (sc) injection of placebo to canakinumab on Day 1. Patients 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. Patients completing the 12 weeks core study were allowed to continue to be treated in another 12 weeks extension study for any new gout flare on demand with the same treatment as assigned in the core study.
Patients under this arm who agreed to continue to 2nd extension period of 12 months, were switched to canakinumab 150 mg sc for any new gout flare during this period Triamcinolone acetonide was not to be administered in the 48-week session.
干预措施: Placebo to canakinumab (Drug)
结局指标
主要结局
Time to First New Flare
时间窗: 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.
Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS)
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 ANCOVA analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates.
Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall)
时间窗: 24 weeks overall
This was the primary endpoint of both extension studies. 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. 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.
Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall)
时间窗: 72 weeks overall
This was the primary endpoint of both extension studies. 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. 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 First Intake of Rescue Medication After the Last Post Baseline Flare.(72 hours post-dose for the last post-baseline flare (during 24 weeks overall))
- Patient's Assessment of Gout Pain Intensity in the Most Affected Joint on a Visual Analog Scale (VAS) in Extension(72 hours post-dose for the last post-baseline flare (during 24 weeks overall))
- 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 (0-100mm VAS)(From baseline to 7 days post dose (randomization))
- Time to Complete Resolution of Pain(7 days post-dose (randomization))
- Percentage of Participants With Complete Resolution of Pain(7 days post-dose (randomization))
- Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks(12 weeks)
- Mean Number of New Gout Flares Per Patient(12 weeks)
- SF36 Physical Function Score at Week 12(Week 12)
- Time to First New Flare(24 weeks)
- Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study(24 weeks)
- Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale)(Last post-baseline flare (during 24 weeks overall))
- Amount of Rescue Medication Taken(7 days last post-baseline flare (during 24 weeks))
- Percentage of Participants Who Took Rescue Medication(during 12 weeks core, 24 weeks overall)
- High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall(72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall))
- Physician's Global Assessment of Response to Treatment(72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall))
- Patient's Global Assessment of Response to Treatment(72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall))
- Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint(72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall))
- Physician's Assessment of Range of Motion of the Most Affected Joint(72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (24 weeks overall))
- Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale)(7 days post dose (randomization), 24 weeks post-dose)
- Time to First New Flare: Survival Analysis by Treatment (72 Weeks Overall)(72 weeks overall)
- Flare Rate Per Year(72 weeks overall)
- High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab(24 hours, 72 hours, 7 days, 4 weeks, 8 weeks and 12 weeks post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall))
- Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab(24 hours, 72 hours, 7 days, 4 weeks, 8 weeks and 12 weeks post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall))
- Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab(72 hours post-dose , 7 days post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall))
- Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale)(72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall))
- Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab(72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall))
- Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab(72 hours post-dose , 7 days post dose last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall))
- Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab(72 hours post-dose , 7 days post dose last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall))
- Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab(72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall))