A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Velmanase Alfa in Patients With Alpha Mannosidosis
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 主要终点
- Change in serum level of total immunoglobulin (Ig)G level
研究概览
简要总结
Randomized, double-blind, placebo-controlled, parallel group study where subjects will receive velmanase alfa or placebo for 24 weeks.
Each subject undergoes to 8 complete visits at the clinic for clinical, laboratory and functional assessments. Study treatment is administered weekly through i.v. infusions
详细描述
A Screening visit (V1) will take place 7±3 days prior to randomization in order to give the subject enough time to consider their participation in the study, to plan the next visits including the long-stay visits at V2, V5 and V8 (long-stay visits as PK and certain tests are performed over more than one day), and to allow the clinic center to complete the evaluation of the eligibility criteria.
Upon confirmation of eligibility, subjects will be randomized to receive weekly i.v. administration of either velmanase alfa 1 mg/kg or placebo.
Thereafter, subjects will undergo weekly visits for administration of study treatment and safety data collection. Clinical, laboratory and functional assessments will be performed at the 4-weekly assessment visits with each subject undergoing a minimum of 8 assessment visits (V1 to V8).
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
Randomized using IRT system
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of alpha-mannosidosis based on alpha mannosidase activity <10% of normal in leukocytes or fibroblasts or through genetic testing;
- •Capability to comply with the protocol;
- •Evidence of informed consent provided by subject or legally authorized guardian(s) prior to performance of any trial-related activities.
排除标准
- •Previous hematopoietic stem cells transplantation (HSCT) with positive outcome;
- •Major surgery planned within 3 months prior to study entry or planned during the study that, in the opinion of the Investigator, would preclude participation in the trial;
- •Known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition that would preclude participation in the study in the Investigator's judgment;
- •Pregnant (as evident by a positive urine hCG or serum-hCG test) or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential [WOCBP]) UNLESS they are willing to use highly effective birth control methods;
- •Participation in other interventional trials testing investigational medicinal products (IMPs) within the last 6 months;
- •Total IgE >800 IU/ml;
- •Any hypersensitivity to velmanase alfa or its excipients that, in the judgment of the Investigator, places the subject at an increased risk for adverse reactions
- •Clinically active infection and recent vaccinations (within the last month before screening).
研究组 & 干预措施
Velmanase alfa
干预措施: Velmanase Alfa (Drug)
placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change in serum level of total immunoglobulin (Ig)G level
时间窗: 24 weeks (end of study)
Efficacy of velmanase alfa compared with placebo in alpha mannosidosis subjects based on serum levels of total immunoglobulin (Ig)G after 24 weeks of velmanase alfa treatment
Change in concentration of serum oligosaccharides
时间窗: 24 weeks (end of study)
To evaluate the efficacy of velmanase alfa compared with placebo after 24 weeks of velmanase alfa treatment as measured by Level of serum oligosaccharides;
次要结局
- Change in Intracellular level of oligosaccharides in peripheral blood leukocytes(24 weeks (end of study))
- Change in serum IgG Subclasses(24 weeks (end of study))
- Incidence of Infections(24 weeks (end of study))
- Assessment of PK parameter Maximum plasma Concentration [Cmax](24 weeks (end of study))
- Assessment of PK parameter Area Under the Curve [AUC](12 weeks)
- Assessment of PK parameter Elimination half-life [t1/2](24 weeks (end of study))
- Assessment of PK parameter trough concentration (Ctrough)(24 weeks (end of study))