A 2-week Single-blind, Randomized, 3-arm Proof of Concept Study of the Effects of AIN457 (Anti-IL17 Antibody), ACZ885 (Canakinumab, Anti-IL1b Antibody), or Corticosteroids in Patients With Polymyalgia Rheumatica, Followed by an Open Label Phase to Assess Safety and Long Term Efficacy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Polymyalgia Rheumatica Activity Score (PMR-AS)
研究概览
简要总结
The study is a two-week, single-blinded, double-dummy, randomized, active-controlled, parallel group design, with a follow-up period up to a total study duration of 6-month, non-randomized, open-label phase to monitor safety, tolerability and, in responders, flare. It is a multicentric, multinational study. The protocol will seek to enroll a total of 30 patients, who will be randomized to the 3 arms at a ratio of 1:1:1.
Patients will have a maximum screening period of 7 days with randomization at D1 for a dosing period of 15 days followed by a follow up-period of 154 days, or 4 months (112 days) after their last biologic dose, whichever is greater, and followed by unblinded re-dosing in the case of a disease flare.
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, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must meet all of the following features:
- •Patients ≥ 50 and ≤ 85 years
- •C-reactive protein (CRP) > 1.0 mg/dl OR erythrocyte sedimentation rate (ESR) > 30 mm/hr
- •New bilateral shoulder and/or hip pain
- •Early morning stiffness ≥ 60 min
- •Duration of illness > 1 week
- •A negative 5 U purified protein derivative skin test (PPD) skin test (≤ 5 mm induration) at screening
排除标准
- •Active infection or current use of antibiotics
- •Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatits B virus (HBV)
- •Previous therapy with methotrexate or other immunosuppressive agents within three months prior to baseline
- •History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix within five years prior to study entry
- •Presence of rheumatoid arthritis or other inflammatory arthritic processes (features of Giant Cell Artertitis (GCA), spondyloarthropathies), connective tissue disease, drug-induced myopathies, endocrine disorders, neurological disorders, chronic pain syndromes, as assessed by base line screening including thyroid-stimulating hormone (TSH), creatine kinase (CK), rheumatoid factor (RF), cyclic citrullinated peptide (CCP), antinuclear antibodies (ANA), serum protein electrophoresis, urinalysis.
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
ACZ885
On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
干预措施: AIN457 (Drug)
ACZ885
On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
干预措施: Placebo (Drug)
AIN457
On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
干预措施: ACZ885 (Drug)
AIN457
On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
干预措施: Placebo (Drug)
Prednisone
On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
干预措施: Prednisone (Drug)
Prednisone
On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
干预措施: Placebo (Drug)
结局指标
主要结局
Polymyalgia Rheumatica Activity Score (PMR-AS)
时间窗: Baseline, Day 15
The efficacy of a single dose of AIN457 and ACZ885 (canakinumab) was measured by the polymyalgia rheumatica activity score. A composite PMR-AS was developed from the following components: measure of C-reactive protein (CRP), measure of Erythrocyte Sedimentation Rate (ESR), assessment of early morning stiffness, assessment of the patient's elevation on upper limbs, patient's assessment of pain, and physician's global assessment of disease activity. Treatment effect was measured by the percent reduction in PMR-AS. N=3 for the ACZ885 arm because CRP values at Day 15 were missing for 2 participants.
次要结局
- Time to Partial Clinical Response(Day 15)
- Time to First Flare(6 months)
- Comparison Between the Initial Response to AIN457 and ACZ885 and the Response After Re-dosing of AIN457 and ACZ885 - Assessed by the Number of Flares After Redosing.(6 months)
- Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ) - % Change From Baseline in the Standard Disability Score at EOS / Month 6(6 months)
- Number of Flares Over a 6 Month Period(6 months)
- Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Deaths(6 months)
- Effect on Health-related Quality of Life Via the Short Form-36 (SF-36) Questionnaire(6 months)
- Pharmacokinetics of AIN457 and ACZ885 - Cmax(Day 15)
- Time to Complete Clinical Response(Day 15)
- Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ)(baseline and at month 6)
- Pharmacokinetics of AIN457 and ACZ885 - Tmax(Day 15)
- Pharmacokinetics of AIN457 and ACZ885 - Vz(Day 15)
- Pharmacokinetics of AIN457 and ACZ885 - T1/2(Day 15)
- Mean Steroid Dose Over a 6 Month Period(6 months)
- Pharmacokinetics of AIN457 and ACZ885 - AUCinf and AUClast(Day 15)
- Pharmacokinetics of AIN457 and ACZ885 - CL(Day 15)