2024-520109-37-00招募中2 期
A Phase 2b, Multicenter, Double-blind, Randomized, Placebo controlled Study to Assess the Efficacy and Safety of Weekly Doses of GLM101 Administered Intravenously to Participants with PMM2-CDG
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 10
- 主要终点
- Change from Baseline in ICARS at 24 weeks
研究概览
简要总结
To characterize the change from Baseline in ataxia at 24 weeks, comparing GLM101 to placebo in participants with PMM2-CDG as assessed by ICARS
入排标准
- 年龄范围
- 0 years 至 65+ years（0-17 Years, 18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •1.Participant is aged ≥ 4 years old at the time of signing the consent
- •2.Participant with molecular diagnosis of PMM2-CDG. Diagnosis is defined as biallelic pathogenic and/or likely pathogenic variants, or, in the case of variants of uncertain pathogenicity, demonstration of biallelic variants and PMM2 enzyme activity consistent with a diagnosis of PMM2-CDG. Diagnosis with laboratory report(s) on file is required.
- •3.Participant is willing and capable of completing the ICARS in its entirety without any assessment deemed as “not evaluable”.
- •4.Participant screening total ICARS score is ≥ 20 and ≤ 80
- •5.Male or female participant has appropriate measures in place to prevent pregnancy
- •6.If the participant is male, he must agree to refrain from donating sperm during the study and 50 days after the last infusion
- •7.The participant is willing and able to provide informed consent/assent, directly or through his/her legally authorized representative (LAR)
- •8.The participant has a caregiver who is willing and able to complete questionnaires and provide the informed consent
排除标准
- •1.Has uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric or other significant disease based on the investigator judgment
- •2.Diagnosis of CDG other than PMM2; Diagnosis is defined as biallelic pathogenic and/or likely pathogenic variants, or, in the case of variants of uncertain pathogenicity, demonstration of biallelic variants and the defined CDG enzyme activity consistent with a diagnosis of the CDG other than PMM2 CDG
- •3.Has a history of liver transplant
- •4.Has an active infection requiring parenteral antibiotics, antivirals, antifungals or treatment with systemic steroids within 7 days prior to screening
- •5.Has a history of drug or alcohol use disorder within 12 months prior to screening
- •6.Has had a major surgical procedure within 30 days prior to screening or an upcoming planned major surgery
- •7.Previous history of GLM101 administration
- •8.Is currently participating in another interventional clinical study or has completed another clinical study with an investigational drug or device within 30 days or 5 halflives (whichever is longer) before enrollment.
- •9.Have consumed products or supplements containing mannose or biotin within 2 weeks prior to screening
- •18.If female, must not be breastfeeding
- •Estimated glomerular filtration rate (eGFR) <45 mL/min/ 1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at screening
- •10.Elevated liver function tests: ALT or AST > 3 × ULN OR total bilirubin > 2 × ULN or INR > 1.5
- •20.Persons who have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
- •Has screening laboratory value(s) considered clinically significant and not related to PMM2-CDG based on the investigator judgment
- •Has serology positive for hepatitis B surface antigen or hepatitis C antibody during screening
- •13.Has a QT interval by Fridericia (QTcF) ≥ 450 ms, or other electrocardiogram (ECG) abnormalities judged as clinically significant by the investigator
- •14.Has history or presence, upon clinical evaluation, of any illness that might impact the safety of GLM101 infusion or evaluability of drug effect based on the investigator’s and Sponsor’s Medical Monitor’s discretion
- •15.Participant weighs above 75 kg
- •16.Participant has a known or suspected hypersensitivity to GLM101 or any components of the formulation used
- •17.Any other reason for which, in the investigator’s opinion, makes the participant unsuitable for study participation
结局指标
主要结局
Change from Baseline in ICARS at 24 weeks
Change from Baseline in ICARS at 24 weeks
次要结局
- 1. Change from Baseline in GRO at 24 weeks
- 2.Change from Baseline in SARA at 24 weeks
- 3.Changes from Baseline in participants and caregiver global impression of change (overall, ataxia, and gross motor function) and global impression of severity (ataxia and gross motor function) and clinician global impression of improvement (overall), global impression of change (ataxia and gross motor function), and global impression of severity (ataxia and gross motor function) at 24 weeks
- 4.Evaluation of safety throughout 24 weeks through the collection of safety parameters: o AEs, AESIs (including IARs), SAEs, deaths, and discontinuations due to AEs o Clinical safety laboratory tests o Immunogenicity o ECG, vital signs, and PE findings
- 5.Change from Baseline to Week 24 compared to the change from Week 24 to Week 48 in ICARS for participants who switched from placebo to GLM101 treatment at Week 24
- 6.Change from Baseline in ICARS for participants randomized to placebo in Part A and who switched to active treatment in Part B compared to change from Baseline in ICARS in participants who were randomized to GLM101 from the beginning of the study in order to compare the GLM101 effect between the early start group and the delayed start group
- 7. Visit-wise changes from Baseline in ICARS up to 48 weeks of GLM101 treatment in participants who were initially randomized to GLM101
- 8. Change from Baseline to Week 24 compared to the change from Week 24 to Week 48 in GRO for participants who switched from placebo to GLM101 treatment at Week 24
- 9. Change from Baseline in GRO for participants randomized to placebo in Part A and who switched to active treatment in Part B compared to change from Baseline in GRO in participants who were randomized to GLM101 from the beginning of the study in order to compare the GLM101 effect between the early start group and the delayed start group
- 10. Visit-wise changes from Baseline in GRO up to 48 weeks of GLM101 treatment in participants who were initially randomized to GLM101
- 11. Change from Baseline to Week 24 compared to the change from Week 24 to Week 48 in SARA for participants who switched from placebo to GLM101 treatment at Week 24
- 12. Change from Baseline in SARA for participants randomized to placebo in Part A and who switched to active treatment in Part B compared to change from Baseline in SARA in participants who were randomized to GLM101 from the beginning of the study in order to compare the GLM101 effect between the early start group and the delayed start group
- 13. Visit-wise changes from Baseline in SARA up to 48 weeks of GLM101 treatment in participants initially randomized to GLM101
- 14.Visit-wise changes in participants and caregiver global impression of change (overall, ataxia and gross motor function) and global impression of severity (ataxia and gross motor function) and clinician global impression of improvement (overall), global impression of change (ataxia and gross motor function), and global impression of severity (ataxia and gross motor function) up to 48 weeks of dosing
- 15.Evaluation of safety through 48 weeks of GLM101 treatment through the collection of safety parameters: o AEs, AESIs (including IARs), SAEs, deaths, and discontinuations due to AEs o Clinical safety laboratory tests o Immunogenicity o ECG, vital signs, and PE findings
- 16.Concentrations of total M1P to estimate PK parameters including Cmax, Clast, tmax, tlast, t1/2, AUC0-last, AUC0-∞, AUC0-tau, CL, Vz, Vss, and λz
研究者
Rose Marino
Scientific
Glycomine Inc.
研究点 (10)
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