A Randomized, Double-blind, Active-control, Multicenter, Efficacy and Safety Study of 2 Dose Levels of Subcutaneous Anakinra Compared to Intramuscular Triamcinolone in the Treatment of Acute Gouty Arthritis, Followed by an Extension Period of up to 2 Years
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 165
- 试验地点
- 37
- 主要终点
- Change in Patient-assessed Pain Intensity in the Index Joint From Baseline to 24-72 Hours for the First Gout Flare Treated in the Study as Measured by VAS
研究概览
简要总结
The purpose of this study is to evaluate how anakinra relieves pain for patients with acute gout that cannot take non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine. The patients will be divided in different treatment groups to compare anakinra to the available drug triamcinolone.
详细描述
Patients will be randomized to treatment at their first gout flare in the study. The first treatment period will be followed by an extension period during which the patients will receive the same treatment for any subsequent flares within 52 weeks of randomization of last patient in the study. The extension period for the individual patient in the study will be maximum two years (104 weeks). Each new flare treated will initiate a new series of study visits and assessments according to specified schedule of events. Only if a patient experience a new flare after Day 15 of the latest flare they can start a new treatment period. The comparison of primary interest is between anakinra (100 mg and 200 mg combined) and 40 mg triamcinolone, and as a secondary objective the 2 different doses of anakinra will be evaluated as well as assessment for subsequent flares.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Informed consent
- •Patient meeting the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) 2015 gout classification criteria
- •History of ≥1 self-reported flares of gouty arthritis within 12 months
- •Current ongoing flare of gouty arthritis characterized by pain intensity
- •Currently tender and swollen joint
- •Onset of current flare within 4 days
- •Intolerant, unresponsive, contraindicated or not appropriate for treatment with NSAIDs and colchicine (both treatment options)
- •If on urate-lowering therapy, on a stable dose and regimen
- •Women of childbearing potential willing to use adequate contraception
- •Inclusion criteria for treatment of subsequent flare(s)
- •Current flare of gouty arthritis characterized by pain intensity
- •Currently tender and swollen joint
- •Women of childbearing potential willing to use adequate contraception
排除标准
- •Use of specified pain relief medications or biologics (including glucocorticoids, narcotics, paracetamol/acetaminophen, NSAIDs, colchicine, IL-blockers and tumor necrosis factor inhibitors) within specified periods prior to randomization
- •Contraindication to triamcinolone
- •Polyarticular gouty arthritis involving more than 4 joints
- •Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis
- •History of malignancy within the past 5 years. Exceptions are basal cell skin cancer, carcinoma-in-situ of the cervix or low-risk prostate cancer after curative therapy.
- •Known hypersensitivity to Escherichia coli-derived proteins, Kineret® (anakinra), Kenalog® (triamcinolone acetonide) or any components of the products.
- •Known presence or suspicion of active or recurrent bacterial, fungal or viral infections, including tuberculosis, or HIV infection or hepatitis B or C infection
- •Presence of severe renal function impairment chronic kidney disease (CKD) stages 4 and 5
- •Presence of neutropenia
- •Uncontrolled clinically significant hematologic, pulmonary, endocrine, metabolic, gastrointestinal, central nervous system or hepatic disease
- •History of myocardial infarction, unstable angina, cerebrovascular events, or coronary artery bypass grafting, New York Heart Association (NYHA) class III or IV heart failure within the previous 3 months
- •Patients who have undergone major surgery within 2 weeks, or have an unhealed operation wound/s
- •Presence of any medical or psychological condition or laboratory result that in the opinion of the investigator might create risk to the patients or to the study.
- •Earlier or current treatment with anakinra
- •Pregnant or lactating women
- •History of >12 flares overall in the 6 months prior to randomization
- •Exclusion criteria for treatment of subsequent flare(s):
- •Known presence or suspicion of active or recurrent bacterial, fungal or viral infections, including tuberculosis, or HIV infection or hepatitis B or C infection.
- •Presence of severe renal function impairment CKD stages 4 and 5
- •Presence of neutropenia
- •History of myocardial infarction, unstable angina, cerebrovascular events, or coronary artery bypass grafting, NYHA class III or IV heart failure within the previous 3 months
- •Patients who have undergone major surgery within 2 weeks or have an unhealed operation wound/s.
- •Pregnant or lactating women.
- •Presence of any condition or laboratory result that in the opinion of the investigator makes the patient not appropriate for treatment
研究组 & 干预措施
Anakinra 100 mg
1 subcutaneous injection of Anakinra 100 mg once daily for 5 days, 1 subcutaneous injection of Placebo to Anakinra 100 mg once daily for 5 days and 1 single intramuscular injection of Placebo to Triamcinolone Acetonide 40 mg
干预措施: Anakinra 100 mg (Drug)
Anakinra 100 mg
1 subcutaneous injection of Anakinra 100 mg once daily for 5 days, 1 subcutaneous injection of Placebo to Anakinra 100 mg once daily for 5 days and 1 single intramuscular injection of Placebo to Triamcinolone Acetonide 40 mg
干预措施: Placebo to Anakinra 100 mg (Drug)
Anakinra 100 mg
1 subcutaneous injection of Anakinra 100 mg once daily for 5 days, 1 subcutaneous injection of Placebo to Anakinra 100 mg once daily for 5 days and 1 single intramuscular injection of Placebo to Triamcinolone Acetonide 40 mg
干预措施: Placebo to Triamcinolone Acetonide 40 mg (Drug)
Anakinra 200 mg
2 subcutaneous injections of Anakinra 100 mg (2 syringes) once daily for 5 days and 1 single intramuscular injection of Placebo to Triamcinolone Acetonide 40 mg
干预措施: Anakinra 100 mg (Drug)
Anakinra 200 mg
2 subcutaneous injections of Anakinra 100 mg (2 syringes) once daily for 5 days and 1 single intramuscular injection of Placebo to Triamcinolone Acetonide 40 mg
干预措施: Placebo to Triamcinolone Acetonide 40 mg (Drug)
Triamcinolone 40 mg
2 subcutaneous injections of Placebo to Anakinra 100 mg once daily for 5 days and 1 single intramuscular injection of Triamcinolone Acetonide 40 mg
干预措施: Triamcinolone Acetonide 40 mg (Drug)
Triamcinolone 40 mg
2 subcutaneous injections of Placebo to Anakinra 100 mg once daily for 5 days and 1 single intramuscular injection of Triamcinolone Acetonide 40 mg
干预措施: Placebo to Anakinra 100 mg (Drug)
结局指标
主要结局
Change in Patient-assessed Pain Intensity in the Index Joint From Baseline to 24-72 Hours for the First Gout Flare Treated in the Study as Measured by VAS
时间窗: At baseline (pre-dose) and at 24, 48 and 72 hours for the first gout flare treated in the study
Patients will score their pain intensity in the joint most affected at baseline (index joint) on a 0-100 mm visual analogue scale (VAS), ranging from no pain (0) to unbearable pain (100). Average of the assessments performed at 24, 48 and 72 hours.
次要结局
- Median Time to Onset of Effect(From baseline (predose) up to Day15 of the first flare treated in the study)
- Median Time to First Intake of Rescue Medication From First Investigational Drug Administration(From Day 1 to Day 15 for the first flare treated)
- Change From Baseline in the Inflammatory Biomarker C Reactive Protein(baseline (predose) and at 72 hours, Day 8 and Day 15 for the first flare treated in the study)
- Serum Concentration of Endogenous Interleukin-1 Receptor Antagonist /Anakinra(Baseline (predose) and at 72 hours, Day 8, Day 15, Day 28 and Week 12 for the first flare and subsequent flares treated during the extension period)
- Change From Baseline in Health Related Quality of Life EuroQol 5 Dimensions 5 Levels (EQ-5D-5L)(at baseline, Day 8 and Day 15 for the first flare treated in the study)
- Median Time to Response(From baseline (predose) up to Day15 of the first flare treated in the study)
- Physician's Assessment of Clinical Signs in Index Joint: Tenderness(at 72 hours, Day 8 and Day 15 for the first flare treated in the study)
- Physician's Assessment of Clinical Signs in Index Joint: Erythema(at 72 hours, Day 8 and Day 15 for the first flare treated in the study)
- Change From Baseline in the Inflammatory Biomarker Serum Amyloid A(baseline (predose) and at 72 hours, Day 8 and Day 15 for the first flare treated in the study)
- Proportion of Patients With Anti-drug Antibodies (ADA) Against Anakinra(Baseline (predose) and at 72 hours, Day 8, Day 15, Day 28 and Week 12 for the first flare and subsequent flares treated treated during the extension period)
- Change in Patient-assessed Pain Intensity in the Index Joint From Baseline at Time Points From 6 Hours to 8 Days for the First Gout Flare Treated in the Study as Measured by 5-point Likert Scale(At baseline (pre-dose) and at 6, 12, 18, 24, 36, 48 and 72 hours and Day 5, 6, 7 and 8 for the first gout flare treated in the study)
- Median Time to Resolution of Pain(From baseline (predose) up to Day15 of the first flare)
- Physician's Assessment of Global Response to Treatment(At 72 hours, Day 8 and Day 15 for the first flare treated in the study)
- Physician's Assessment of Clinical Signs in Index Joint: Swelling(at 72 hours, Day 8 and Day 15 for the first flare treated in the study)
- Proportion of Patients With Neutralizing Antibodies(Baseline (predose) and at 72 hours, Day 8, Day 15, Day 28 and Week 12 for the first flare and subsequent flares treated during the extension period)
- Health Care Resource Utilization Due to a Gouty Arthritis Flare(Recorded up to Day 15 for the first flare and subsequent flares treated during the extension period)
- Patient´s Assessment of Global Response to Treatment (5-point Likert Scale)(at 72 hours, Day 8 and Day 15 for the first flare treated in the study)
- The Percent of Patients With at Least One Adverse Event(Through study completion, at 12 weeks after last flare treated during the extension period)
- The Percent of Patients With at Least One Serious Adverse Event, Including Death(Through study completion, at 12 weeks after last flare treated during the extension period)
- Change From Baseline in Short Form (36) Health Survey, Acute Version 2 (SF-36®) Physical Functioning Domain Score(at baseline, Day 8 and Day 15 for the first flare treated in the study)
- Percent Impairment While Working During Last Week Due to Gout During the First Flare and Subsequent Flares(Recorded up to Day 15 for the first flare and subsequent flares treated during the extension period)