Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in Patients With Resistance to Eculizumab Due to Complement C5 Polymorphisms
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Measurement of Ratio of LDH to the Upper Limit of Normal (ULN)
研究概览
简要总结
Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in patients with resistance to Eculizumab due to complement C5 polymorphisms.
详细描述
Coversin, a small protein complement C5 inhibitor which prevents the cleavage of C5 by C5 convertase into C5a and C5b, will be used in an open label, non-comparative clinical trial in patients with PNH and proven resistance to eculizumab due to C5 polymorphisms. Patients will be treated with Coversin by daily subcutaneous injection for 6 months in order to determine the safety and efficacy of the drug in these circumstances. If satisfactory control of the PNH is achieved, and at the discretion of the Principal Investigator (PI), patients will have the option of remaining on Coversin and being entered into the long term follow-up study for 2 years.
Please note, 'Coversin' is used throughout, but Nomacopan is the official name/INN.
Please note, the end points were assessed for 6 months, but the adverse events were measured over the 2 year period.
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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with known Paroxysmal Nocturnal Haemoglobinuria (PNH)
- •LDH >=1.5 Upper Limit of Normal (ULN)
- •Resistance to Eculizumab proven by both a recognised C5 polymorphism on genetic screening and complement inhibition on CH50 ELISA of <100% at concentrations of Eculizumab in excess of 50 μg/mL
- •Willing to self-inject Coversin daily or to receive daily subcutaneous injections by a home nurse or in a doctor's office or hospital clinic
- •Males or females taking adequate contraceptive precautions if of childbearing potential, 18 - 80 years of age
- •Body weight ≥50kg and ≤ 100kg
- •The patient has provided written informed consent.
- •Willing to avoid prohibited medications for duration of study
- •Must agree to take appropriate prophylactic precautions against Neisseria infection.
- •Must be counselled regarding the possible reproductive risks of using Coversin and be advised to use an adequate method of contraception pending further data on reproductive toxicology.
排除标准
- •Body weight <50kg or>100kg
- •Pregnancy (females)
- •Failure to satisfy the PI of fitness to participate for any other reason
- •Known allergy to ticks or severe reaction to arthropod venom (e.g., bee or wasp venom)
研究组 & 干预措施
Coversin (Nomacopan)
This is an open label, non-comparator study.
Patient will be given a single ablating dose of 0.57mg/kg per subject followed by daily repeat maintenance doses. The initial repeat dose will be 25% of the ablating dose. If this is insufficient to maintain complement inhibition at ≤10% of baseline (pre-treatment) level after 5 days of treatment the daily dose will be increased by doubling until that level of inhibition is achieved. In the event of 100% inhibition being achieved the dose may be titrated downwards at the PI's discretion until a satisfactory clinical result is obtained. If at any point in treatment complement inhibition falls to less than 50% of baseline a further ablating dose of 0.57mg/kg should be given. Coversin lyophilised powder in each vial was diluted with 0.6 mL water for injection prior to use.
干预措施: Coversin (Drug)
结局指标
主要结局
Measurement of Ratio of LDH to the Upper Limit of Normal (ULN)
时间窗: Day 0 and Day 28
LDH is an indicator of disease progression in patients with PNH and is expected to fall to within 2x upper limit of normal (ULN) within 28 days in successfully treated patients. Units are measured in ratio of LDH:ULN, where the ULN is 250 U/L. The primary efficacy endpoint was the LDH AUC from Day 0 to 28 compared with 28 days pretreatment. Data for the 28 days pre-treatment was not collected, and as only one patient was recruited, the LDH values compared with baseline and the ratio of LDH to the Upper Limit of Normal (ULN) are presented.
Number and Type of Adverse Events (AE)
时间窗: 2 years
The number and type of reported AEs will be recorded as well as the opinion of the Principle Investigator (PI) as to their possible relationship to the study drug.
次要结局
- Measurement of Haptoglobin (Hp) at Days 28, 90 and 180, Absolute and Change From Baseline(Baseline, Day 28, Day 90 and Day 180)
- Measurement of Lactate Dehydrogenase (LDH) at Baseline, Day 90 and Day 180(Baseline, Day 90 and Day 180)
- Dependency on Blood Transfusion(Day 0 through to study completion (2 years))
- Measurement of Haemoglobin (Hb) at Days 28, 90, and 180, Absolute and Change From Baseline(Baseline, Day 28, Day 90 and Day 180)
- Change in Quality Of Life Questionnaire (QOQ) Score at Days 0, 28, 90 and 180(Day 28, 90 and 180)
- Change in Functional Assessment of Chronic Illness Therapy (FACIT) Score at Days 0, 28, 90 and 180(Day 28, 90 and 180)