Multi-centre, Open-label Trial to Assess the saFety, Pharmacodynamics, Efficacy and Pharmacokinetics of pegunigaLsidase Alfa in Patients From 2 Years to Less Than 18 Years of Age With Confirmed FabrY Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 22
- 试验地点
- 21
- 主要终点
- Change from baseline in LVMi as assessed by echocardiogram
研究概览
简要总结
A Study to Learn About the Safety and Effects of the Study Drug PRX-102 in Children and Adolescents with Fabry Disease.
详细描述
This study aims to learn how safe pegunigalsidase alfa (PRX-102 for short) is and how it works at treating Fabry disease in children and adolescents.
PRX-102 is an enzyme replacement therapy (ERT), meaning it acts like a natural enzyme. PRX-102 is given through a needle placed in a vein (intravenous infusion) every two weeks.
The main questions this study aims to answer are:
- Which is the safest and most effective dose to be given to children and adolescents.
- Which effects PRX-102 has on signs and symptoms of Fabry disease (e.g. renal and cardiac function, pain, gastrointestinal symptoms)
20 to 22 boys and girls with Fabry disease between the ages of 2 and 17 will be part of this study. There will be three age cohorts, with children aged 2 to 7 years included (enrolled) in Cohort A, children aged 8 to 12 years in Cohort B, and adolescents aged 13 to less than 18 years in Cohort C.
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
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with the provision of informed consent from their legal guardians
- •Boys and girls aged 2 to 7 years (Cohort A), 8 to 12 years (Cohort B), or 13 to <18 years (Cohort C).
- •Confirmed diagnosis of Fabry disease
- •Presence of at least one of the following characteristic features of Fabry disease: neuropathic pain, cornea verticillata, and/or clustered angiokeratoma.
- •History of Fabry pain: Fabry crises OR chronic pain.
- •Clinical condition that, in the investigator's opinion, requires ERT treatment.
排除标准
- •All Subjects:
- •Estimated glomerular filtration rate (eGFR) at screening < 80 mL/min/1.73 m
- •History of type I hypersensitivity reactions (anaphylactic or anaphylactoid life-threatening reaction) to other ERT treatment for Fabry disease or any component of the study drug.
- •Initiation of treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) or a dose change in ongoing treatment in the four weeks before screening.
- •Urine protein to creatinine ratio (UPCR) > 0.5 g/g (0.5 mg/mg or 500 mg/g) if not treated with an ACE inhibitor or ARB.
- •Currently taking another investigational drug for any condition.
- •History of acute kidney injury in the 12 months before screening, including specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic renal diseases); non-specific conditions (e.g., ischaemia, toxic injury); or extrarenal pathology (e.g., prerenal azotaemia, acute postrenal obstructive nephropathy).
- •History of renal dialysis or kidney transplantation.
- •History of or current malignancy requiring treatment.
- •Severe cardiomyopathy or significant unstable cardiac disease within six months before screening.
- •A positive test for Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) within three months before screening.
- •Presence of any medical, emotional, behavioural, or psychological condition that, in the Investigator's judgement, could interfere with the subject's compliance with the requirements of the study.
- •Additional Exclusion Criteria for Subjects Enrolled in Stage I:
- •Non-classic form of Fabry disease
- •Receipt of treatment for Fabry disease within six months before screening
- •Positive for anti-PRX-102 antibodies at screening
- •Additional Exclusion Criteria for Subjects in Stage II (i.e., non-treatment naïve males or females):
- •Unwilling to discontinue current ERT treatment for Fabry disease before baseline.
- •Females: Pregnant or lactating, or of childbearing potential with a fertile male partner and unwilling to use a highly reliable method of contraception from the informed consent signature until 30 days after the last infusion.
研究组 & 干预措施
Single Arm - Pegunigalsidase alfa (PRX-102)
For Cohort C, PXR-102 administered every two weeks at 1.0 mg/kg is believed to be the minimum effective dose.
For Cohorts A and B, the starting dose will be 1.0 mg/kg every two weeks but it may be adjusted on the outcomes of Stage I, with the support of the Data Safety Monitoring Board.
干预措施: PRX-102 1 mg/kg every two weeks (Drug)
结局指标
主要结局
Change from baseline in LVMi as assessed by echocardiogram
时间窗: Baseline and 12 Months
Echocardiogram parameters include left ventricular mass index (LVMi)
Incidence of Treatment Emergent Adverse Events (TEAEs)
时间窗: 12 Months
Incidence of Infusion Related Reactions (IRRs)
时间窗: 12 Months
Incidence of Injection site reactions (ISRs)
时间窗: 12 Months
Change in Tanner stage
时间窗: Baseline and 12 Months
Tanner Staging of Sexual Development will be used to assess sexual development (i.e. breast development (B1 to B5) and pubic hair development (Ph-1 to Ph-5) in females and pubic hair and genetical development (G1-G5) in males.
Change from baseline of 12-lead ECG quantitative parameters: Mean Heart Rate
时间窗: Baseline and 12 Months
Change from baseline of 12-lead ECG quantitative parameters: PR Interval
时间窗: Baseline and 12 Months
Change from baseline of 12-lead ECG quantitative parameters: QRS Duration
时间窗: Baseline and 12 Months
Change from baseline of 12-lead ECG quantitative parameters: QT Interval
时间窗: Baseline and 12 Months
Change from baseline of 12-lead ECG quantitative parameters: QTc Interval
时间窗: Baseline and 12 Months
Change from baseline of 12-lead ECG quantitative parameters: ST Segment
时间窗: Baseline and 12 Months
Incidence of treatment-emergent Anti-Drug Antibodies (ADAs)
时间窗: Baseline and 12 Months
Incidence of premedication use at each visit and change of infusion premedications from baseline
时间窗: Baseline and 12 Months
Pharmacokinetics: Time to maximum plasma concentration (tmax)
时间窗: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Pharmacokinetic : Area under the plasma concentration-time curve from time 0 to time t (AUC0 t)
时间窗: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Pharmacokinetics: Area under the curve from time 0 to 2 weeks (AUC0-2wk)
时间窗: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Pharmacokinetics: Area under the curve from time 0 to infinity (AUC0-∞)
时间窗: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Pharmacokinetics: Terminal half-life (t1/2)
时间窗: Baseline, week 2, week 4, week 12, week 26 and week 52]
Pharmacokinetics: Area under the curve over a dosing interval (AUCτ)
时间窗: Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Pharmacokinetics: Observed drug concentration at the end of the dosing interval (Cτ)
时间窗: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Pharmacokinetics: Clearance (Cl)
时间窗: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Pharmacokinetics: Volume of distribution (Vz)
时间窗: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Change in eGFR
时间窗: Baseline and 12 Months
Change in annualized eGFR slope
时间窗: Baseline and 12 Months
Change in urine albumin levels
时间窗: Baseline and 12 Months
Change in urine protein levels
时间窗: Baseline and 12 Months
Incidence of any cardiac arrythmias as assessed by Holter ECG
时间窗: Baseline and 12 Months
Change in plasma levels of cardiac biomarkers
时间窗: Baseline and 12 Months
High-sensitivity cardiac troponin T (hs-cTnT) and N- terminal pro brain natriuretic peptide (NT-Pro BNP) will be assessed.
Change in plasma level of Gb3 concentration (nM)
时间窗: Baseline and 12 Months
Change in plasma level of lyso-Gb3 (nM)
时间窗: Baseline and 12 Months
Change in urine level of lyso-Gb3 (nM)
时间窗: Baseline and 12 Months
Incidence of change from baseline in the number of different pain medications
时间窗: Baseline and 12 Months
Incidence of Fabry Clinical Events
时间窗: 12 Months
FCEs are classified into four categories: renal, cardiac, cerebrovascular and death due to non-cardiac reasons
Change from baseline of Mainz Severity Score Index (MSSI) scores
时间窗: Baseline and 12 Months
Domains (general, neurological, cardiovascular, renal dysfunction)
Change from baseline of PedsQL-GI (or GSRS for subjects who reaches 18 yrs of age) scores
时间窗: Baseline and 12 Months
Change from baseline of FPHPQ scores
时间窗: Baseline and 12 Months
Change from baseline of PedsQL-PPQ (or BPI-SF for subjects who reaches 18 yrs of age) scores
时间窗: Baseline and 12 Months
Change from baseline of EQ-5D-Y (or EQ-5D-5L for subjects who reaches 18 yrs of age) scores
时间窗: Baseline and 12 Months
次要结局
未报告次要终点