Study Protocol for a Multi-Centre, Placebo-Controlled Phase II Study of Canakinumab for the Treatment of Adult-onset Still's Disease (AOSD) Including an Open-label Long Term Extension
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 36
- 试验地点
- 14
- 主要终点
- Core Study Part I: Percentage of Responders as Assessed by Disease Activity Score 28 Joints (DAS28) Score at Week 12
研究概览
简要总结
The purpose of this trial is to investigate the efficacy of the treatment with canakinumab in participants with Adult-onset Still's Disease (AOSD) and active joint involvement.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written and signed consent from the participant to take part in the study
- •Men and women aged ≥ 18 years and ≤ 75 years
- •Fulfilment of AOSD classification criteria (according to Yamaguchi et al, J. Rheumatology, 1992)
- •Disease activity based on Disease Activity Score 28 (DAS28) of ≥3.2 at screening
- •At least 4 painful and 4 swollen joints at screening and baseline (of the 28 joints according to DAS28)
- •If undergoing treatment with non-steroidal anti-inflammatory drugs (NSAIDs), stable dose for at least 4 weeks prior to randomisation
- •If undergoing treatment with glucocorticoids, stable dose of ≤10 milligrams per day (mg/day) (prednisolone or equivalent) for at least 4 weeks prior to randomisation
- •If undergoing treatment with conventional disease-modifying anti-rheumatic drugs (DMARD), stable dose for at least 3 months prior to randomisation
- •Normalisation period for biological DMARDS (anakinra 1 week, etanercept 1 month, adalimumab and certolizumab 2 months, infliximab, golimumab, abatacept and tocilizumab 3 months, rituximab 9 months, canakinumab 6 months) prior to randomisation
- •In participants of reproductive age, use of an effective method of contraception as well as negative pregnancy test prior to the study commencing.
排除标准
- •Previous treatment with the study drug with repeated administration of canakinumab
- •Intraarticular or intravenous administration of glucocorticoids within 4 weeks prior to the baseline or use of narcotic analgesics except for analgesics permitted within the framework of the investigation (codeine and tramadol)
- •Presence of another, serious chronic-inflammatory disease
- •Positive hepatitis B antigen (HBsAg), hepatitis C antibodies and/or human immunodeficiency virus (HIV) antibodies.
- •Presence of a relevant, active infection or other diseases, which entail a tendency towards infection
- •Positive screening for latent tuberculosis, in accordance with usual local practice
- •Raised liver count (raised bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3-fold the normal range)
- •Serum-creatinine concentration >1.5 milligrams per deciliter (mg/dL)
- •Inadequate haematological findings (hemoglobin [Hb] ≤ 10 grams per deciliter (g/dL), neutrophils ≤2,500/microliter (µl) and thrombocytes ≤100,000/µl)
- •Simultaneous participation in any other interventional clinical study within the last 30 days preceding the commencement of the study
- •History of neoplasia with the exception of a curatively treated non-melanoma skin tumour or carcinoma of the cervix treated in situ without any indication of recurrence within the last 10 years
- •Relevant cardiac or pulmonary disorders
- •Severe intercurrent neurological or psychiatric disorders
- •Macrophage activation syndrome (MAS) as part of previous treatment with IL-1 blockade (e.g. anakinra, rilonacept)
- •Vaccination with a live vaccine within 3 months before the baseline
- •Alcohol or drug abuse in the past 12 months
- •≥400 milliliter (mL) donation of blood or loss up to 8 weeks before the baseline
- •Pregnancy or breast-feeding
- •Commitment of the patient to an institution at the direction of an authority or court
研究组 & 干预措施
Canakinumab
Participants received canakinumab 4 mg/kg up to a maximum of 300 mg subcutaneous (SC) injection, once in morning on Day 0, Weeks 4, 8, and 12 in Part I of the core study. Participants with response (change in DAS score > 1.2 at Week 12) continued to receive same dose of canakinumab in Part II for Weeks 12, 16, and 20. Participants who had remission (change in DAS score > 1.2 and no signs of systemic activity for adult-onset Still's disease at Week 20) entered Long-term extension (LTE) phase and received same dose of canakinumab at Weeks 24 and 28, which was down titrated to 2 mg/kg if applicable from Week 28 up to Month 27.
干预措施: Canakinumab (Drug)
Placebo
Participants received placebo, SC injection, once in morning on Day 0, Weeks 4, 8, and 12 in Part I of the core study. Participants with response (change in DAS score > 1.2 at Week 12) continued to receive placebo at Weeks 12, 16, and 20. Non-responders (who had change in DAS score ≤ 1.2) were unblinded to receive canakinumab 4 mg/kg (up to 300 mg maximum), SC injection, at Weeks 12, 16, and 20. Participants who had remission (change in DAS score > 1.2 and no signs of systemic activity for adult-onset Still's disease at Week 20) entered Long-term extension (LTE) phase and received same dose of canakinumab at Weeks 24 and 28, which was down titrated to 2 mg/kg if applicable from Week 28 up to Month 27.
干预措施: Canakinumab (Drug)
Placebo
Participants received placebo, SC injection, once in morning on Day 0, Weeks 4, 8, and 12 in Part I of the core study. Participants with response (change in DAS score > 1.2 at Week 12) continued to receive placebo at Weeks 12, 16, and 20. Non-responders (who had change in DAS score ≤ 1.2) were unblinded to receive canakinumab 4 mg/kg (up to 300 mg maximum), SC injection, at Weeks 12, 16, and 20. Participants who had remission (change in DAS score > 1.2 and no signs of systemic activity for adult-onset Still's disease at Week 20) entered Long-term extension (LTE) phase and received same dose of canakinumab at Weeks 24 and 28, which was down titrated to 2 mg/kg if applicable from Week 28 up to Month 27.
干预措施: Placebo (Drug)
结局指标
主要结局
Core Study Part I: Percentage of Responders as Assessed by Disease Activity Score 28 Joints (DAS28) Score at Week 12
时间窗: Week 12
Responders included participants with change in disease activity score based on 28 joint counts and ESR (DAS28) score \> 1.2. The DAS28 score index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity score, and the erythrocyte sedimentation rate (ESR) value. Total score ranged between 0-10. A DAS28-ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value \< 2.6 = disease remission.
次要结局
- Core Study Part I: CFB in Serum Ferritin Level at Week 12(Week 12)
- Core Study Part I: Percentage of Responders With Fever Episodes(Week 12)
- Core Study Part I: CFB in ACR Component: 66 Swollen Joint Count (SJC)(Baseline, Weeks 4, 8 and 12)
- Core Study Part I: CFB in American College of Rheumatology (ACR) Component: 68 Tender Joint Count (TJC)(Baseline, Weeks 4, 8 and 12)
- Core Study Part I: CFB in the 28 TJC(Baseline, Weeks 4, 8 and 12)
- Core Study Part I: CFB in the 28 SJC(Baseline, Weeks 4, 8 and 12)
- Core Study Part I: CFB in ACR Component: Physician's Global Assessment of Disease Activity Score(Baseline, Weeks 4, 8 and 12)
- Core Study Part I: CFB in ACR Component: Participant's Global Assessment of Disease Activity Score(Baseline, Weeks 4, 8 and 12)
- Core Study Part I: Percentage of Responders With ACR90(Baseline, Week 12)
- Core Study Part I: CFB in DAS28 C-reactive Protein (CRP) Score(Baseline, Weeks 4, 8 and 12)
- Core Study Part I: Percentage of Responders With American College of Rheumatology Response of 20 (ACR20)(Baseline, Week 12)
- Core Study Part I: Change in Joint Mobility (Degrees of Motion) Assessed by Neutral Zero Method(Baseline, Week 12)
- Core Study Part I: Change From Baseline (CFB) in Disease Activity Score 28 Joints Erythrocyte Sedimentation Rate (DAS28 [ESR]) Score(Baseline, Weeks 4, 8 and 12)
- Core Study Part I: CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score(Baseline, Week 12)
- Core Study Part I: Percentage of Responders With ACR30(Baseline, Week 12)
- Core Study Part I: Percentage of Responders With Modified ACR30(Baseline, Week 12)
- Core Study Part I: CFB in ACR Component: Acute Phase Reactant CRP(Baseline, Weeks 4, 8 and 12)
- Core Study Part I: CFB in ACR Component: Acute Phase Reactant ESR(Baseline, Weeks 4, 8 and 12)
- Core Study Part I: CFB in ACR Component: Participant's Global Assessment of Pain Score(Baseline, Weeks 4, 8 and 12)
- Core Study Part I: Percentage of Responders With ACR50(Baseline, Week 12)
- Core Study Part I: Percentage of Responders With ACR70(Baseline, Week 12)
- Core Study Part I: Percentage of Responders With European League Against Rheumatism (EULAR) Response(Baseline, Week 12)
- Core Study Part I: Percentage of Responders Achieving Low Disease Activity (LDA)(Week 12)
- Core Study Part I: Percentage of Responders Achieving Disease Remission and Extended Disease Remission(Week 12)
- Core Study Part I: CFB in Medical Outcome Short Form (SF-36) Health Survey Score(Baseline, Week 12)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Month 27)
研究者
Eugen Feist
Prof. Dr Eugen Feist
Charite University, Berlin, Germany