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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 432
- 试验地点
- 31
- 主要终点
- Core Study: Mean Number of Gout Flares Per Participant
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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^
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Canakinumab (Drug)
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.
干预措施: Allopurinol (Drug)
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.
干预措施: Placebo Matching Canakinumab (Drug)
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.
干预措施: Placebo Matching Colchicine (Drug)
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.
干预措施: Canakinumab (Drug)
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.
干预措施: Allopurinol (Drug)
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.
干预措施: Placebo Matching Canakinumab (Drug)
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.
干预措施: Placebo Matching Colchicine (Drug)
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.
干预措施: Canakinumab (Drug)
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.
干预措施: Allopurinol (Drug)
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.
干预措施: Placebo Matching Canakinumab (Drug)
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.
干预措施: Placebo Matching Colchicine (Drug)
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.
干预措施: Canakinumab (Drug)
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.
干预措施: Allopurinol (Drug)
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.
干预措施: Placebo Matching Canakinumab (Drug)
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.
干预措施: Placebo Matching Colchicine (Drug)
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.
干预措施: Canakinumab (Drug)
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.
干预措施: Allopurinol (Drug)
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.
干预措施: Canakinumab (Drug)
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.
干预措施: Placebo Matching Canakinumab (Drug)
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.
干预措施: Placebo Matching Colchicine (Drug)
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.
干预措施: Canakinumab (Drug)
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.
干预措施: Allopurinol (Drug)
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.
干预措施: Placebo Matching Colchicine (Drug)
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.
干预措施: Colchicine (Drug)
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.
干预措施: Allopurinol (Drug)
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.
干预措施: Placebo Matching Canakinumab (Drug)
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.
干预措施: Canakinumab (Drug)
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.
干预措施: Canakinumab (Drug)
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.
干预措施: Colchicine (Drug)
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.
干预措施: Colchicine (Drug)
结局指标
主要结局
Core Study: Mean Number of Gout Flares Per Participant
时间窗: 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.
次要结局
- Core Study: Percentage of Participants With Gout Flare at Different Time Points(Days 2, 4, 6, and Weeks 2, 4, 6, 10, and 16 of the core study)
- Core Study: Mean Number of Gout Flares for the Repeat Dose Regimen of Canakinumab as Compared to the Single Doses of Canakinumab(up to 16 weeks after randomization)
- Extension Study: Amount of Rescue Medication Taken(Baseline of the extension study until the end of the study (up to 24 weeks))
- Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares(Baseline of the core study to Week 16)
- Extension Study: Participant's Assessment of Gout Pain on a 100 mm Visual Analog Scale During the First Flare(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(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(Baseline of the extension study until the end of the study (up to 24 weeks))
- Core Study: Percentage of Participants With at Least 1 Gout Flare Within 16 Weeks After Randomization(Baseline of the core study to Week 16)
- Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares(Baseline of the core study to Week 16)
- Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale(Days 15, 29, 57, 85, 113, and 141 of the core study)
- Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare(Baseline of the extension study until the end of the study (up to 24 weeks))