Safety and Efficacy Evaluation of Intravenous GLM101 in Patients with PMM2-CDG: A Phase 2 Open-Label Extension Study
- Trial ID
- 2024-512171-12-00
- Protocol
- GLM101-007
- Sponsor
- Glycomine Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to examine the **safety** of GLM101 in patients with PMM2-CDG who have previously received GLM101. This is clinically relevant as it aims to ensure that the treatment does not pose undue risks to patients, thereby supporting its potential use in managing PMM2-CDG, a rare congenital disorder of glycosylation.
Secondary objectives include:
- To examine changes in coordination and balance (ataxia), which are critical for assessing the impact of GLM101 on motor function and quality of life in affected individuals.
- To measure the sugar delivered by GLM101 in participants with PMM2-CDG, which is important for understanding the pharmacodynamics and therapeutic efficacy of the treatment.
Participants
The clinical trial involves a total of **36 participants** diagnosed with **PMM2-CDG**, a rare genetic disorder. The study population includes both male and female subjects, with an age range of 2 to 65 years. Participants were selected based on their previous completion of a treatment period with GLM101 in a prior clinical study and a molecularly confirmed diagnosis of PMM2-CDG. The trial does not specifically target a vulnerable population. Participants are required to adhere to medically accepted methods of contraception if applicable, and males must agree to refrain from donating sperm during the study and for a specified period afterward. The trial does not impose specific lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants are willing and able to comply with the study protocol, providing a focused and relevant cohort for examining the safety of GLM101 in this patient population.
Plans and Procedures
The clinical trial is designed as a **Phase 2, open-label extension study** to assess the safety and efficacy of GLM101, administered intravenously to participants with PMM2-CDG. The trial will involve participants who have successfully completed a previous treatment period with GLM101. The study will span an estimated duration from September 2024 to March 2029. Participants will be involved in the study for a maximum treatment period of 48 weeks, with the primary objective being the collection of safety information, including adverse events, vital signs, and laboratory tests. Secondary endpoints include changes in the International Co-operative Ataxia Rating Scale (ICARS) and the amount of Mannose-1-Phosphate in the blood.
The trial will commence with an inclusion (screening) visit to confirm eligibility, which includes a molecularly confirmed diagnosis of PMM2-CDG and an age range of 2-65 years. Participants must provide informed consent and comply with specific contraceptive requirements if applicable. Following the screening, participants will undergo regular follow-up visits every 3-6 months to monitor safety and efficacy parameters. The end-of-study visit will conclude the participant's involvement, with a final assessment of safety and efficacy outcomes.
Participants may be terminated early from the study if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The study is not a low-intervention trial and involves the administration of GLM101 via **intravenous use**. The maximum daily dose is set at 30 mg/kg, and the study will not include a pediatric formulation. The trial is sponsored by Glycomine Inc., and GLM101 is classified as an orphan drug for the treatment of PMM2-CDG.
Treatment
The clinical trial involves the administration of **GLM101**, an experimental medication designed for the treatment of PMM2-CDG. **GLM101** is formulated as an **injection/infusion** and is administered via the **intravenous route**. The active substance in **GLM101** is **alfa-d-mannopyranosyl phosphate dipotassium**, a chemical compound. The dosing regimen for **GLM101** involves a maximum daily dose of 30 mg/kg, with a total maximum dose of 30 mg/kg over the treatment period. The treatment period is set to a maximum of 48 weeks. The medication is not formulated specifically for pediatric use. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.
In addition to the experimental treatment, the study may involve the use of **liposomal mannose-1-phosphate** as a non-experimental treatment. This substance serves as a comparator or adjunctive therapy to evaluate the efficacy and safety of **GLM101**. The administration details, including dosage and frequency, for **liposomal mannose-1-phosphate** are not specified in the provided data. Participant compliance with all study medications is closely monitored to ensure the integrity of the trial results.
Efficacy
Efficacy in the clinical trial will be assessed using specific secondary endpoints. These include changes in the International Co-operative Ataxia Rating Scale (ICARS), which will be evaluated every 3 to 6 months and compared to baseline measurements taken before treatment with GLM101. Additionally, the amount of **Mannose-1-Phosphate** in the blood, a component of GLM101, will be measured at Month 6. These parameters will provide insights into the therapeutic impact of GLM101 on participants with PMM2-CDG. The data collection and analysis will be conducted at specified intervals to monitor the progression and response to the treatment regimen.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Is willing and able to provide informed consent/assent, directly or through a legally authorized representative
- Has successfully completed the Treatment Period with GLM101 in a previous clinical study.
- At least 2 years of age inclusive, at the time of signing the informed consent form (ICF).
- 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 including from a prior parent trial is permitted;
- Male or female participant has appropriate measures in place to prevent pregnancy: 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)) or becomes of childbearing potential during the study, 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: True abstinence: 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 participant. Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- Male or female participant has appropriate measures in place to prevent pregnancy: 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.
- Male or female participant has appropriate measures in place to prevent pregnancy: if the participant is a sexually active (or becomes sexually active during the study) 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 GLM101. 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 comply with this protocol.
Exclusion Criteria
- Has any other condition that would, in the opinion of the Investigator, potentially compromise the safety or compliance of the participant or preclude the participant’s successful completion of the study
- Has a history of drug or alcohol use disorder within the 12 months prior to Screening
- If not enrolling directly from a parent study (i.e., if more than 28 days from Final Treatment visit in a parent study to date of consent), has had a major surgical procedure within 30 days prior to Screening
- Has 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 not enrolling directly from a parent study (i.e., if more than 28 days from Final Treatment visit in a parent study to date of consent), has serology positive for hepatitis B surface antigen or hepatitis C antibody during Screening;
- 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;
- Weight exceeds 120 kg.
- Participant is unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, other study procedures, and study restrictions.
- If female, and breastfeeding
- Is currently participating in another interventional clinical study or has completed another clinical study with an investigational drug or device (other than GLM101) within 30 days or 5 half-lives before GLM101 infusion
- Must not have a hypersentivity to GLM101 or anti-histamine pre-medication.
- Has a history of a severe allergic reaction to any drug or excipients of GLM101 (as listed in the GLM101 IB);
- 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
- If not enrolling directly from a parent study (i.e., more than 28 days from Final Treatment visit in a parent study to date of consent), has an active infection requiring parenteral antibiotics, antivirals, or antifungals or treatment with systemic steroids within 7 days prior to Screening;
- ALT or AST >3× ULN OR total bilirubin >2× ULN or INR >1.5 (if no anti-coagulation treatment) or INR > 4 (if participant on anti-coagulation treatment) considered clinically significant;
- Has a history of liver transplant
- Persons who have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities;
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Yet Recruiting | 30 Sept 2024 | 3 |
 France | Not Yet Recruiting | 30 Sept 2024 | 2 |
 Germany | Not Yet Recruiting | 30 Sept 2024 | 6 |
 Italy | Not Yet Recruiting | 30 Sept 2024 | 8 |
 Portugal | Recruiting | 30 Sept 2024 | 5 |
 Spain | Recruiting | 30 Sept 2024 | 39 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
GLM101 | Test | INJECTION/INFUSION | INTRAVENOUS USE | 30 | 48 | PRD11189218 |
GLM101 | Test | INJECTION/INFUSION | INTRAVENOUS USE | 30 | 48 | PRD13183389 |