Open-Label Extension Study to Assess GLM101 in PMM2-CDG Patients

A Phase 2, Open-Label Extension Study to Assess the Safety and Efficacy of GLM101 Administered Intravenously to Participants With PMM2-CDG

The goal of this clinical trial is to provide continued access to GLM101 to treat PMM2-CDG in people who have previously received GLM101 in other trials and learn about the long term effect of GLM101. Participants will complete weekly infusions of GLM101 at the same dose level received in previous trials.

Study Overview

• Status: Enrolling by invitation
• Conditions: Pmm2-CDG; Phosphomannomutase 2 Deficiency
• Intervention / Treatment: Drug: 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 provide continued access to study treatment. Participants will receive 30 mg/kg. Dose levels may be adjusted to lower doses or higher doses based on available data that demonstrates a change to be safe and favorable. Among other assessments, participants will be asked to complete questionnaires to evaluate changes in ataxia and quality of life.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze
• France
  • Paris, France, 75015
    • AP-HP Hopital Universitaire Necker-Enfants Malades
• Germany
  • Münster, Germany, 48149
    • Universitaetsklinikum Münster
• Italy
  • Catania, Italy, 95124
    • Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana
• Portugal
  • Porto, Portugal, 4099-001
    • Unidade Local de Saúde de Santo António, E.P.E
• Spain
  • Esplugues de Llobregat, Spain, 08950
    • Hospital Sant Joan de Déu
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre - Unidad Pediatrica de Investigacion y Ensayos Clinicos (UPIC)
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital for Children
• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • New York, New York, United States, 10029
      • The Icahn School of Medicine at Mount Sinai
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia (CHOP)
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Is willing and able to provide informed consent/assent, directly or through a legally authorized representative.
2. Has successfully completed the Treatment Period with GLM101 in a previous clinical study.
3. At least 2 years of age, at the time of signing the informed consent form (ICF).
4. 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;

5. 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.
   • 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.
6. 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.
7. Is willing and able to comply with this protocol.

Exclusion Criteria:

Participants who meet any of the following criteria will be excluded from participation in the study:

1. 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.
2. 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.
3. 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;
4. 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;
5. Has a history of liver transplant;
6. Has a history of drug or alcohol use disorder within the 12 months prior to Screening;
7. 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;
8. Has laboratory value(s) outside the laboratory reference range considered clinically significant and not related to PMM2-CDG;
9. If female, has a positive serum pregnancy test during Screening.
10. If female, and breastfeeding.
11. 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.
12. Has a hypersensitivity to anti-histamine pre-medication.
13. Has a history of a severe allergic reaction to any drug or excipients of GLM101 (as listed in the GLM101 IB);
14. 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;
15. Has a QTc ≥ 450 ms, or other clinically significant ECG abnormalities;
16. Has uncontrolled cardiovascular, hepatic, pulmonary, gastro-intestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric or other significant disease;
17. Weight exceeds 120 kg.
18. Persons who have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
19. Participant is unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, other study procedures, and study restrictions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 30 mg/kg GLM101; GLM101 IV infusions, given weekly	Drug: GLM101; GLM101 IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate long-term safety	Number of participants with treatment related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	From enrollment to end of treatment up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate changes in ataxia using International Cooperative Ataxia Rating Scale (ICARS)	The scale is scored out of 100 with 19 items and 4 subscales of postural and gait disturbances, limb ataxia, dysarthria, and oculomotor disorders. Higher scores indicate higher levels of impairment.	From enrollment, at 3 months, 6 months and annually to end of treatment up to 4 years
Maximum observed plasma concentration (Cmax)	Assessment of the pharmacokinetics (PK) of GLM101	From enrollment to end of treatment up to 4 years
Time to maximum observed plasma concentration (Tmax)	Assessment pharmacokinetics (PK) of GLM101	From enrollment to end of treatment up to 4 years
Area under the plasma concentration vs. time curve (AUC)	Assessment of the pharmacokinetics (PK) of GLM101	From enrollment to end of treatment up to 4 years

Collaborators and Investigators

• Sponsor: Glycomine, Inc.
• Investigators: Study Director: Chief Medical Officer, Glycomine, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2024
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: October 22, 2024
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 26, 2024

Study Record Updates

• Last Update Posted (Actual): September 15, 2026
• Last Update Submitted That Met QC Criteria: September 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Pmm2; CDG; GLM101; CDG 1a
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Carbohydrate Metabolism, Inborn Errors; Congenital disorder of glycosylation type 1A
• Other Study ID Numbers: GLM101-007

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No