A 24-month Multicenter, Open-label Phase II Trial Investigating the Safety and Efficacy of Repeated Velmanase Alfa (Recombinant Human Alpha-mannosidase) Treatment in Pediatric Patients Below 6 Years of Age With Alpha-Mannosidosis

Chiesi Farmaceutici S.p.A.0 个研究点目标入组 5 人开始时间: 2016年12月最近更新: 2021年10月26日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: Chiesi Farmaceutici S.p.A.
入组人数: 5
主要终点: Safety and tolerability of velmanase alfa as per Adverse events

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

The main objectives of the study are to evaluate safety and efficacy of repeated treatment with recombinant human alfa-mannosidase of patients with alfa-mannosidosis aged less than 6 years

详细描述

The Primary endpoints of the study include:

Safety and tolerability of velmanase alfa as per Adverse events (AEs, including IRR), vital signs, laboratory parameters (hematology, biochemistry and urinanalysis)
Detection of anti-velmanase alfa antibodies and neutralizing/inhibitory antibodies

The Secondary endpoints include changes from baseline to 24 months for the following parameters. Efficacy outcomes:

Serum oligosaccharides
Functional capacity: Peabody Developmental Motor Scale - 2nd edition (PDMS-2) scores, Mullen's Scale of Early Learning (MSEL) scores, Bruininks-Oseretsky Test Of Motor Proficiency-2nd Edition (BOT-2), when applicable by age (from 4 years) or upon the judgment of the physician
Endurance: 3-Minute Stair Climb Test (3MSCT) and 6-Minute Walk Test (6MWT) in pediatric patients from 4 years of age, or when applicable according to the judgment of the physician, 2-Minute Walk Test (2MWT) in pediatric patients below 4 years of age, or when applicable according to the judgment of the physician
Hearing evaluation: Otoacoustic Emissions (OAE) testing, Automatic Auditory Brainstem Response (A-ABR) audiometry
Immunological profile, when applicable upon the judgment of the physician:
CSF biomarkers: Tau protein (Tau), Neurofilament Protein Light (NFL), Glial Fibrillary Acidic Protein (GFAp), Oligosaccharides
Assessment of quality of life via Questionnaire to parents
Assessment of mannose-rich oligosaccharides in brain tissue, MRI
Pharmacokinetic parameters

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: — 至 6 Years（Child）
性别: All
接受健康志愿者: 否

入选标准

•Patient's custodial parent(s) must provide signed ICF prior to the involvement of the patient in any trial-related activities
•The subject's custodial parent(s) must have the ability to comply with the protocol
•The subject must have a confirmed diagnosis of alpha-mannosidosis as defined by alpha-mannosidase activity in leukocytes or fibroblasts < 10% of normal activity (historical data)
•The subject must have an age at the time of screening < 6 years.

排除标准

•The subject's diagnosis cannot be confirmed by alpha-mannosidase activity < 10% of normal activity
•Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-mannosidosis
•History of BMT
•Presence of known clinically significant cardiovascular, hepatic, pulmonary, or renal disease or other medical conditions that, in the opinion of the Investigator, would preclude participation in the trial
•Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
•Planned major surgery that, in the opinion of the Investigator, would preclude participation in the trial
•Participation in other interventional trials testing the IMP within the last 3 months.

研究组 & 干预措施

Velmanase Alfa

Experimental

velmanase alfa 1mg/kg body weight infusion

干预措施: Velmanase Alfa (e.g. Lamazym) (Drug)