A Long-Term Study with GLM101 in Patients with PMM2-CDG

Phase 2

Recruiting

Conditions: PMM2-CDG

Registration Number: 2024-512171-12-00

Lead Sponsor: Glycomine Inc.

Brief Summary: • To examine the safety of GLM101 in PMM2-CDG patients who previously received GLM101

Detailed Description: This is a phase 2 open-label clinical study of GLM101 in patients with PMM2-CDG who have previously participated in a study of GLM101. This study is designed to monitor long-term safety and treatment effect of GLM101 and provided continued access to study treatment. Participants will continue weekly infusions of GLM101 at the same dose level they received in the previous study. Dose levels may be adjusted to lower doses or higher doses based on available data that demonstrates a change to be safe and tolerable. Participants will be asked to complete questionnaires to evaluate changes in ataxia and quality of life.

Recruitment & Eligibility

Status: Ongoing, recruiting

Sex: Not specified

Target Recruitment: 39

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.

Ages 2-65 years, 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;

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 subject. Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods 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 (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, 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.

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 75 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, 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;

Has a history of liver transplant

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Collection of the safety information from the collection of Side effects (or Adverse Events), deaths, and stopping the study due to side effects; Tests from blood and urine (hematology, chemistry, and urinalysis) (compared to before treatment with GLM101); ECG (heart tracings), vital signs (blood pressure, heart rate, and body temperature), and physical exam changes (compared to before treatment with GLM101)		Collection of the safety information from the collection of Side effects (or Adverse Events), deaths, and stopping the study due to side effects; Tests from blood and urine (hematology, chemistry, and urinalysis) (compared to before treatment with GLM101); ECG (heart tracings), vital signs (blood pressure, heart rate, and body temperature), and physical exam changes (compared to before treatment with GLM101)

Secondary Outcome Measures

Name	Time	Method
Changes in International Co-operative Ataxia Rating Scale, ICARS (evaluated every 3-6 months, compared to before treatment with GLM101)		Changes in International Co-operative Ataxia Rating Scale, ICARS (evaluated every 3-6 months, compared to before treatment with GLM101)
The amount of Mannose-1-Phosphate (the sugar contained in a lipid bubble, which together make up GLM101) in blood (evaluated at Month 6)		The amount of Mannose-1-Phosphate (the sugar contained in a lipid bubble, which together make up GLM101) in blood (evaluated at Month 6)

Trial Locations

Locations (1): Sant Joan De Deu Barcelona Hospital
🇪🇸
Esplugues De Llobregat, Spain
Sant Joan De Deu Barcelona Hospital
🇪🇸Esplugues De Llobregat, Spain
Mercedes Serrano Guimare
Site contact
+34936009733
mercedes.serrano@sjd.es