GLM101 for Phosphomannomutase 2 Deficiency

Recruiting at 12 trial locations

Overseen By Director Clinical Operations

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Glycomine, Inc.

Must not be taking: Antibiotics, Antivirals, Antifungals, Steroids

Disqualifiers: Uncontrolled diseases, Liver transplant, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is evaluating the safety, effectiveness, and how the body absorbs, distributes, and eliminates GLM101, for participants with PMM2-CDG, including children, adolescents, and adults. Researchers will compare participants receiving GLM101 to those receiving a placebo to see if GLM101 improves symptoms of PMM2-CDG. The study includes two treatment parts: a 24-week double blind placebo-controlled treatment period (Part A), and a 24-week open-label phase where every participant will receive GLM101(Part B).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you should avoid products or supplements containing mannose or biotin within 2 weeks before screening.

What data supports the effectiveness of the treatment GLM101 for Phosphomannomutase 2 Deficiency?

Research suggests that enhancing the concentration of certain molecules like glucose-1,6-bisphosphate can stabilize the enzyme affected in Phosphomannomutase 2 Deficiency, offering a potential treatment approach. This indicates that treatments targeting enzyme stability might be effective. ^{1 2 3 4 5}

How does the drug GLM101 differ from other treatments for phosphomannomutase 2 deficiency?

GLM101 is unique because it may act as a pharmacological chaperone, potentially stabilizing the misfolded PMM2 protein and improving its function, which is a novel approach compared to the current preventive and symptomatic treatments available for PMM2 deficiency. ^{1 2 3 5 6}

Research Team

Chief Medical Officer

Principal Investigator

Glycomine, Inc.

Eligibility Criteria

This trial is for individuals, including children (aged ≥4), with PMM2-CDG—a rare genetic disorder. Participants must have a confirmed molecular diagnosis and be able to complete specific assessments. Women of childbearing potential must use contraception and not be pregnant; men must agree to use contraception.

Inclusion Criteria

I can give my consent or have someone legally authorized to do so on my behalf.

I have a caregiver willing to help with questionnaires and consent.

My ICARS score is between 20 and 80.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Double-blind Treatment (Part A)

Participants receive weekly intravenous infusions of either GLM101 or placebo to assess primary efficacy

24 weeks

Weekly visits for infusions

Open-label Extension (Part B)

All participants receive weekly intravenous infusions of GLM101

24 weeks

Weekly visits for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• GLM101

Trial Overview The study tests GLM101's safety and effectiveness in improving PMM2-CDG symptoms over a 24-week double-blind phase comparing it with placebo, followed by another 24 weeks where all participants receive GLM101 openly.

Participant Groups

Group I: GLM101- 30 mg/kg weekly administered IV in Part A (double-blind) and Part B (open-label) Experimental Treatment 2 Interventions

Group II: Placebo weekly admin. IV in Part A (double-blind); 30 mg/kg weekly admin. IV in Part B (open-label) Placebo Group 2 Interventions

Who Is Running the Clinical Trial?

Glycomine, Inc.

Lead Sponsor

Trials

4

Recruited

250+

Findings from Research

In a study of 22 Danish patients with carbohydrate-deficient glycoprotein syndrome type 1A, specific PMM2 mutations were identified, with none being homozygous for the R141H mutation, suggesting that this genotype may be incompatible with life due to its severe impact on enzyme activity.

Functional analysis revealed that while some mutations like F119L retained 25% of normal PMM2 activity, others like R141H, G117R, and T237R showed no activity, indicating that at least one mutation must allow for residual enzyme function for patient survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbohydrate-deficient glycoprotein syndrome type 1A: expression and characterisation of wild type and mutant PMM2 in E. coli. Kjaergaard, S., Skovby, F., Schwartz, M.[2010]

References

1. United States pubmed.ncbi.nlm.nih.gov

Expression analysis revealing destabilizing mutations in phosphomannomutase 2 deficiency (PMM2-CDG): expression analysis of PMM2-CDG mutations. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Carbohydrate-deficient glycoprotein syndrome type 1A: expression and characterisation of wild type and mutant PMM2 in E. coli. [2010]

3. United States pubmed.ncbi.nlm.nih.gov

Biochemical phenotype of a common disease-causing mutation and a possible therapeutic approach for the phosphomannomutase 2-associated disorder of glycosylation. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Advances in the diagnosis and treatment of phosphomannomutase 2 deficiency]. [2023]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Novel Treatment for Congenital Disorder of Glycosylation in a Patient with Novel Homozygote Mutation of PMM2: A Case Report and Review Literature. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

New and potential strategies for the treatment of PMM2-CDG. [2021]