NCT05549219已完成2 期
A Phase 2, Randomized, Open-Label, 24-Week Study to Assess the Pharmacodynamics, Safety, Tolerability, and Pharmacokinetics of Multiple Doses of GLM101 Administered Intravenously to Adult, Adolescent, and Pediatric Participants With PMM2-CDG
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 4
- 主要终点
- Evaluate changes from baseline in ataxia
研究概览
简要总结
This is a Phase 2, randomized, open-label, 24-week treatment study to evaluate the potential pharmacodynamic (PD) activity, safety, tolerability, and pharmacokinetics (PK) of GLM101 in adult, adolescent, and pediatric, patients with a confirmed diagnosis of PMM2-CDG. The planned doses of GLM101 to be investigated are 10, 20, and 30 mg/kg. The study will consist of a Screening Period, a 24-week (6-month) Treatment Period, and a 30-day (1-month) Follow-Up Period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is male or female, 18 to 65 years of age, inclusive, at Screening (Cohorts 1-3, 7), 12-17 years of age, inclusive, at Screening (Cohort 4) or 2-11 years of age, inclusive, at Screening (Cohorts 5 and 6);
- •Molecularly confirmed 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 bi-allelic variants AND phosphomannomutase-2 (PMM2) enzyme activity consistent with a diagnosis of PMM2-CDG. Historical diagnosis with lab report(s) on file is permitted;
- •If the participant is a female of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile (permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy)) she must not be pregnant (confirmed by a negative serum pregnancy test), is using a medically accepted method of contraception (abstinence, a hormonal contraceptive associated with inhibition of ovulation in conjunction with a barrier method, or use of an intrauterine device), and must agree to continue using this method for 50 days after the last infusion of GLM101; Note: sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception;
- •If the participant is a female of non-childbearing potential, she must be pre-pubertal, surgically sterile, or must have an ovarian dysfunction confirmed by a follicle stimulating hormone (FSH) >40 IU/L and absence of menses for 12 months without an alternative medical cause;
- •If the participant is a sexually active male with female partners, the sexually mature, nonsterile male participant agrees to use a medically acceptable method of contraception (abstinence, the partner taking a hormonal contraceptive in conjunction with a male condom, or use by the partner of an intrauterine device with a male condom) and agrees to continue using this method for 50 days after the last infusion of GLM
- •Males are considered surgically sterile if they have undergone bilateral orchiectomy or vasectomy at least 3 months prior to Screening;
- •If the participant is male, he must agree to refrain from donating sperm during the study and 50 days after the last infusion of GLM101;
- •Is willing and able to provide informed consent/assent, directly or through his/her legally authorized representative.
排除标准
- •Diagnosis of congenital disorder of glycosylation (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 bi-allelic variants AND the defined CDG enzyme activity consistent with a diagnosis of the CDG other than PMM2 CDG.
- •Has an active infection requiring parenteral antibiotics, antivirals, or antifungals or treatment with systemic steroids within 7 days prior to Screening;
- •Has confirmed active coronavirus disease-2019 (COVID-19) or tests positive for severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) at Screening or check in to the clinical site;
- •ALT or AST >3× ULN OR total bilirubin >2× ULN or INR >1.5
- •Has a history of a severe allergic reaction to any drug or excipients of GLM101 (as listed in the GLM101 Investigator's Brochure);
- •Has a known history of poor venous access;
- •Has a history of liver transplant;
- •Has a history of drug or alcohol use disorder within 12 months prior to Screening;
- •Has had a major surgical procedure within 30 days prior to Screening;
- •Has Screening or eligibility confirmation laboratory value(s) outside the laboratory reference range considered clinically significant and not related to PMM2-CDG;
- •If female, has a positive serum pregnancy test during Screening;
- •If female, must not be breastfeeding;
- •Has serology positive for hepatitis B surface antigen or hepatitis C antibody during Screening;
- •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 Medical Monitor's discretion;
- •Has a QTc ≥ 450 ms, or other clinically significant ECG abnormalities;
- •Has uncontrolled cardiovascular, hepatic, pulmonary, gastro-intestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric or other significant disease;
- •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 half-lives before GLM101 infusion.
- •Weight exceeds 75 kg.
研究组 & 干预措施
10 mg/kg GLM101
Experimental
GLM101 IV infusions, given weekly
干预措施: GLM101 (Drug)
20 mg/kg GLM101
Experimental
GLM101 IV infusions, given weekly
干预措施: GLM101 (Drug)
30 mg/kg GLM101
Experimental
GLM101 IV infusions, given weekly
干预措施: GLM101 (Drug)
结局指标
主要结局
Evaluate changes from baseline in ataxia
时间窗: 12 weeks and 24 weeks
Changes in ICARS (International Co-operative Ataxia Rating Scale)
次要结局
- Number of participants with treatment-emergent adverse events assessed by severity and frequency(12 weeks and 24 weeks)
- Maximum observed plasma concentration (Cmax)(over 24 weeks)
- Time to maximum observed plasma concentration (Tmax)(over 24 weeks)
- Area under the plasma concentration vs. time curve (AUC)(over 24 weeks)
研究者
研究点 (4)
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相关资讯
Glycomine Completes Enrollment in Phase 2b POLAR Study of GLM101 for Rare Genetic Disorder PMM2-CDG- Glycomine has completed enrollment of 43 patients in its Phase 2b POLAR study evaluating GLM101 for PMM2-CDG, a rare genetic disorder affecting approximately 50,000 patients worldwide.
- The randomized, double-blind, placebo-controlled trial spans 15 sites globally and will assess improvement in ataxia using the International Cooperative Ataxia Rating Scale over 24 weeks.
- PMM2-CDG causes serious neurological impairments with ataxia affecting more than 90% of patients, and currently has no approved treatments available.
- Topline data from the study is expected in the fourth quarter of 2026, building on encouraging Phase 2a results that showed meaningful improvements in ataxia.5 months agoFDA Grants Fast Track Designation to Glycomine's GLM101 for PMM2-CDG Treatment- The FDA has granted Fast Track designation to Glycomine's GLM101, a mannose-1-phosphate replacement therapy, for treating phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG).
- GLM101 is currently in a Phase 2 clinical study involving adult and adolescent patients, with plans to expand enrollment to pediatric patients aged two years and older.
- Initial data from the Phase 2 study suggests promising clinical benefits with GLM101, showing good tolerability and only mild to moderate adverse events reported to date.
- Fast Track designation will allow for more frequent interactions with the FDA, potentially accelerating the approval process for GLM101, addressing a significant unmet need.2 years ago