A Prospective, Randomized, Double-Blind, Placebo-Controlled, Single-Center Study of Oral Epalrestat Therapy in Pediatric Subjects With Phosphomannomutase 2-congenital Disorder of Glycosylation (PMM2-CDG)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Change in Antithrombin III (ATIII)
研究概览
简要总结
This is a prospective, single-center, randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, and clinical and metabolic improvement of pediatric subjects with PMM2-CDG on oral epalrestat therapy vs. placebo.
详细描述
This is a prospective, single-center, randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, and clinical and metabolic improvement of pediatric subjects with PMM2-CDG on oral epalrestat therapy vs. placebo. The primary study objective is to evaluate the safety and probable benefit of oral epalrestat therapy in pediatric subjects with PMM2-CDG. Study outcomes include evaluating the metabolic improvement of pediatric subjects treated with oral epalrestat therapy compared to placebo, evaluating safety, clinical improvement, and pharmocokinetics (PK) of oral epalrestat therapy in pediatric subjects compared to placebo, and evaluating urine polyols, adverse events, laboratory data, other safety measures, PK, and Quality of Life surveys to measure clinical improvement.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Patients and all study personnel will remain blinded to the original treatment assignment until study close.
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
- •Age ≥ 2 and < 18 years
- •Diagnosis of PMM2-CDG, based on molecularly confirmed biallelic PMM2 pathogenic variants (can be historical diagnosis with lab report on file)
- •Informed consent (and assent, as applicable) document personally signed by the legally authorized representative of the patient, indicating that the patient's parent/guardian has been informed and agreed to all aspects of the study
- •Be willing and able to adhere to the study assessments and schedule described in the protocol and consent/assent documents
- •Negative urine pregnancy test (only for female subjects of child-bearing potential)
- •For subjects of child-bearing potential-only, subject has been counseled on and agrees to the requirement either for double barrier contraceptive methods and/or for total abstinence from prior to randomization through 3-months after the cessation of treatment.
排除标准
- •Known or suspected other known CDG
- •Known allergy to aldose reductase inhibitors
- •Hypersensitivity to epalrestat
- •Hepatic impairment defined as any one of the following:
- •AST/ALT >5x ULN in the 6 months prior to screening
- •Bilirubin >2X ULN in the last 6 months prior to screening
- •Synthetic liver dysfunction (albumin deficiency < 2.8 mmol/L) at screening, or
- •Diagnosis of liver fibrosis (Fibroscan > 7 kPa) confirmed by liver elastogram at screening
- •Renal impairment defined as serum creatinine: > 0.5 mg/dL (≤ 6 years); > 0.7 mg/dL (7-10 years); > 1.24 mg/dL (≥ 11 years)
- •Low platelet count (< 125x109 /L)
- •Any other clinically significant lab abnormality which, in the opinion of the investigator, should be exclusionary
- •Anemia (Hgb < 10 g/dL)
- •Use of an investigational drug, including acetazolamide, in the past 28 days; use of an investigational biologic in the past 12 months
- •Concurrent or planned participation in interventional protocol or use of any other unapproved therapeutics, and,
- •Any other medical condition, which, in the opinion of the investigator, will interfere with the patient's ability to comply with the protocol, compromises patient safety, or interferes with the interpretation of the study results.
研究组 & 干预措施
Epalrestat
Epalrestat will be administered orally, 3 times per day (TID) spaced out as evenly as possible over 24 hours in a divided dose starting on Day 1 of the Study.
干预措施: Epalrestat (Drug)
Placebo
Placebo will be administered orally, 3 times per day (TID) spaced out as evenly as possible over 24 hours in a divided dose starting on Day 1 of the Study.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Antithrombin III (ATIII)
时间窗: 9 months
Change in ATIII from baseline between study arms
Change in sorbitol (mmol/mol creatinine)
时间窗: 9 months
Change in sorbitol from baseline between study arms
Change in ICARS
时间窗: 9 months
Change in ICARS from baseline between study arms
次要结局
- Change of Body Max Index (BMI) percentile(9 months)
- Change of factor XI activity percentage(9 months)
- Change of normalized mannitol (mmol/mol creatinine)(9 months)
- Change in Nijmegen Pediatric CDG Rating Scale (NPCRS) score(9 months)
- Change of liver transaminases (U/L)(9 months)
- Change of transferrin glycosylation (ratio)(9 months)