An Adaptive Dose-ranging, Multi-center, Single-blind, Double-dummy, Active-controlled Trial to Determine the Target Dose of Canakinumab (ACZ885) in the Treatment of Acute Flares in Gout Patients Who Are Refractory or Contraindicated to NSAIDs and/or Colchicine
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 200
- 试验地点
- 29
- 主要终点
- The Dose of Canakinumab for Treatment of Acute Flares in Gout Patients That Leads to the Same Efficacy as Triamcinolone Acetonide With Respect to Pain Intensity on a 0-100 mm Visual Analog Scale (VAS)
研究概览
简要总结
This 8-week study is designed to determine the target dose of canakinumab (ACZ885) for the management of acute flare in gout patients who are contraindicated to Non-Steroidal anti-inflammatory drugs and/or colchicine. The efficacy of ACZ885 will be compared to the corticosteroid triamcinolone acetonide.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of at least 1 gout flare prior to the Screening Visit
- •Meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of acute arthritis of primary gout.
- •Presence of acute gout flare for no longer than 5 days.
- •Baseline pain intensity > or = to 50 mm on the 0-100 mm VAS.
- •Contraindicated for, intolerant or unresponsive to NSAIDs, colchicine or both.
排除标准
- •Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis.
- •Presence of severe renal function impairment
- •Contraindication to intramuscular injection
- •Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment
- •Evidence of active pulmonary disease
- •Live vaccinations within 3 months prior to the start of the study
- •Use of forbidden therapy
- •Other protocol-defined inclusion/exclusion criteria applied
研究组 & 干预措施
Canakinumab 10 mg
Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.
干预措施: Canakinumab (Drug)
Canakinumab 25 mg
Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.
干预措施: Canakinumab (Drug)
Canakinumab 50 mg
Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.
干预措施: Canakinumab (Drug)
Canakinumab 90 mg
Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.
干预措施: Canakinumab (Drug)
Canakinumab 150 mg
Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.
干预措施: Canakinumab (Drug)
Triamcinolone acetonide 40 mg
Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once and placebo matching canakinumab s.c. once, on Day 1.
干预措施: Triamcinolone acetonide (Drug)
结局指标
主要结局
The Dose of Canakinumab for Treatment of Acute Flares in Gout Patients That Leads to the Same Efficacy as Triamcinolone Acetonide With Respect to Pain Intensity on a 0-100 mm Visual Analog Scale (VAS)
时间窗: at 24,48 and 72 hours post-baseline
Mean target dose at 24, 48 and 72 hours. Four models: Emax, Logistic, Linear in log-dose, Linear were selected to describe the potential dose-response curve and hence estimate the target dose of canakinumab using baseline Visual Analog Scale (VAS) and Body Mass Index (BMI) as covariates. Target dose was defined as the dose for which the efficacy is equivalent to the efficacy of triamcinolone acetonide 40 mg and was identified by assessing the dose response relationship with regards to the pain intensity in the target joint measured on a 0- 100 mm VAS (0= no pain and 100= unbearable pain).
次要结局
- The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide(Baseline,at 72 hrs post-dose and 7 days post-dose)
- Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment(at 72 hours post-baseline)
- The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint(Baseline, within 7 days after randomization)
- High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group(at 72 hours and 7 days, 4 and 8 weeks post-dose)
- Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group(at 72 hours and 7 days, 4 and 8 weeks post-dose)
- Amount of Rescue Medication Taken for Each Treatment Group(7 days after study drug administration)