NCT01242813已完成2 期
An Open-label, Multicenter, Efficacy and Safety Study of 4-month Canakinumab Treatment With 6-month Follow-up in Patients With Active Recurrent or Chronic TNF-receptor Associated Periodic Syndrome (TRAPS).
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Complete or Almost Complete Response at Day 15
研究概览
简要总结
This trial will assess the safety and efficacy of ACZ885 in patients with active recurrent or chronic TNF-receptor associated periodic syndrome (TRAPS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient's written informed consent for >or= 18 years of age before any assessment is performed. Parent or legal guardian's written informed consent and child's assent, if appropriate, are required before any assessment is performed for patients < 18 years of age.
- •Male and female patients at least 4 years of age at the time of the screening visit.
- •Patients with a clinical diagnosis of TRAPS and a mutation of TNFRSF1A gene. Patients with low penetrance mutations, such as R92Q or P46L, can be included with mutual agreement between the investigator and Novartis.
- •Patients with a diagnosis of recurrent TRAPS must experience more than 6 episodes/year prior to receiving an effective biologic therapy and the duration of each episode lasted at least 8 days. For patients receiving biologic therapy, this criterion applies to prior to receiving the biologic therapy.
- •Patients who have been treated with anakinra must have demonstrated a partial or complete clinical response with an associated decrease in their inflammation markers (CRP and SAA).
- •Active TRAPS as evidenced by clinical signs and symptoms of active TRAPS (Physician's Global Assessment >or= 2) and an elevated CRP > 10mg/L (Normal CRP range <or= 10 mg/L) and/or SAA > 10 mg/L (Normal SAA range <or= 10 mg/L) at time of first canakinumab treatment.
排除标准
- •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 hCG laboratory test (> 5 mIU/mL).
- •Women of child-bearing potential, defined as pre-menarche females aged 8 years and above or all women physiologically capable of becoming pregnant, UNLESS they are
- •women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner
- •women whose partners have been sterilized by vasectomy or other means
- •using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices [IUDs]; periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods] is not acceptable) or total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensures compliance.
- •Women of child-bearing potential should be willing to use a reliable contraception throughout the study and for 3 months after study drug discontinuation.
- •Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
- •History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result.
- •Positive QuantiFERON (QFT-TB G In-Tube) test or positive Purified Protein Derivative (PPD) test (>or= 5 mm induration) at screening or within 2 month prior to the screening visit, according to the national guidelines. Patients with a positive PPD test (>or= 5 mm induration) at screening may be enrolled only if they have either a negative chest x-ray or a negative QuantiFERON test.
- •Live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose.
- •History of significant other medical conditions, which in the Investigator's opinion would exclude the patient from participating in this trial.
- •History of recurrent and/or evidence of active bacterial, fungal, or viral infection(s).
- •Use of prohibited therapies, any other investigational biologics within 8 weeks prior to the Baseline visit, any other investigational drugs, other than investigational biologic treatment, within 30 days (or 3 months for investigational monoclonal antibodies) or 5 half-lives prior to the Baseline visit, whichever is longer
- •History of known hypersensitivity to canakinumab.
- •History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
- •Other protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Canakinumab
Experimental
This was an open-label, single treatment arm, multicenter study of monthly canakinumab 150 mg (2 mg/kg for patient ≤ 40 kg) subcutaneous injections in patients with active recurrent or chronic TRAPS.
干预措施: ACZ885 (Drug)
结局指标
主要结局
Percentage of Participants With Complete or Almost Complete Response at Day 15
时间窗: Day 15
Complete response was defined as clinical remission and serological remission. Clinical remission was defined as Physician's Global Assessment of TRAPS activity absent or minimal and serological remission was defined as C reactive protein (CRP) and/or Serum amyloid A protein (SAA) to be less than (\<) 10 milligram per liter (mg/L). Almost complete response was defined as clinical remission and a partial serological remission (equal to or more than \[≥\] 70% reduction of baseline CRP and/or SAA).
次要结局
- Serum Concentration of Total Interleukin-1β Antibody (IL-1β)(Day 3, 8, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449, 533, 561, 589, 617, 645, 673, 729, 785, 841, 897, 925 and 953)
- Number of Participants With Anti-canakinumab Antibodies at Any Visit(Day 1 up to Day 953 (End of study))
- Percentage of Participants With Complete or Almost Complete Response at Day 8(Day 8)
- Percentage of Participants With Complete Clinical Remission at Day 8 and 15(Day 8 and Day 15)
- Percentage of Participant With Target Levels of C-reactive Protein (CRP) and Serum Amyloid A Protein (SAA) at Day 8 and 15(Day 8 and Day 15)
- Time to Physician's Assessed Clinical Remission(Baseline up to Day 15)
- Percentage of Participants With Complete or Almost Complete Response at Day 15 After Receiving Additional Dose at Day 8(Day 15)
- Time to Participant's Assessed Clinical Remission(Baseline up to Day 15)
- Percentage Change From Baseline in C-reactive Protein (CRP) and Serum Amyloid A (SAA) Concentration to End of Study(Day 1 up to Day 953 (End of study))
- Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain(Day 113 (end of treatment period) up to Day 925 (End of study))
- Percentage of Participants With Defined Grades in Physician's Global Assessment Score(Day 1 up to Day 953 (End of study))
- Percentage of Participants With Defined Grades in Participant's Global Assessment Score(Day 1 up to Day 253 (End of follow-up period))
- Percentage of Relapsed Participants(Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449,477,505, 533, 561, 589, 617, 645, 673,701, 729,757, 785, 813, 841,869, 897, 925 and 953)
- Time to Relapse After Last Dose of Canakinumab(Day 85 to Day 253 (End of treatment period to Follow-up period))
- Percentage of Participants Who Relapsed and Received Rescue Medication(Day 85 to Day 953 (End of treatment period to End of study))
- Serum Concentration of Canakinumab(Day 3, 8, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449, 533, 561, 589, 617, 645, 673, 729, 785, 841, 897, 925 and 953)
研究者
研究点 (1)
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