GLM101 for Phosphomannomutase 2 Deficiency

Recruiting at 21 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests GLM101, a new treatment for people with PMM2-CDG, a rare genetic disorder affecting sugar processing in the body. The study aims to determine the safety and effectiveness of GLM101 and its movement through the body by comparing it to a placebo (a substance with no active medication) over two phases. Participants will first receive either GLM101 or a placebo for 24 weeks, followed by everyone receiving GLM101 for another 24 weeks. Suitable candidates have a confirmed diagnosis of PMM2-CDG and experience symptoms related to this condition. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in treatment.

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.

Is there any evidence suggesting that GLM101 is likely to be safe for humans?

Research shows that GLM101 is being tested for its safety and effectiveness in treating PMM2-CDG, a rare genetic disorder. This treatment aims to manage symptoms by delivering mannose-1-phosphate into cells. Earlier studies have shown promise for GLM101, and it has received special recognition from health agencies in the U.S. and Europe, indicating its potential benefits.

While detailed safety data is not provided, the trial phase suggests that some previous testing has already occurred, indicating it might be safe enough to proceed. This does not guarantee the absence of risks, but it suggests the treatment is considered safe enough for further testing.

Participants in the study will receive the treatment for 24 weeks in a controlled setting, with close monitoring for any side effects. The treatment will be administered through an IV, a common method for delivering medications in trials. All treatments can have side effects, and joining a trial involves participating in ongoing research to better understand the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Phosphomannomutase 2 Deficiency, like enzyme replacement therapy and supportive care, aim to manage symptoms rather than directly addressing the root cause. GLM101 is unique because it specifically targets the underlying enzyme deficiency by delivering a novel compound intravenously, potentially correcting the metabolic imbalance. Researchers are excited about GLM101 because it offers a more direct and targeted approach, which could lead to more effective management of the condition and improved patient outcomes. Additionally, the potential for GLM101 to be administered weekly as an IV infusion offers a consistent and controlled delivery method, which can enhance its effectiveness compared to existing therapies.

What evidence suggests that GLM101 might be an effective treatment for PMM2-CDG?

Research has shown that GLM101, which participants in this trial may receive, may help treat PMM2-CDG, a genetic disorder affecting sugar processing in the body. Early results from adult patients suggest that this treatment can improve symptoms. GLM101 replaces a specific sugar component, mannose-1-phosphate, to help the body manage sugars better. Ongoing studies indicate its potential effectiveness, offering hope for those with this condition. ^{2 6 7 8 9}

Who Is on the Research Team?

Chief Medical Officer

Principal Investigator

Glycomine, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. glycomine.com glycomine.com/glycomine-announces-encouraging-efficacy-data-from-ongoing-phase-2-clinical-study-in-pmm2-cdg/

Glycomine Announces Encouraging Efficacy Data from ... March 4, 2024. Initial data from adult patients with PMM2-CDG showed promising evidence of clinical benefit with GLM101 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06892288

NCT06892288 | A Study to Assess the Efficacy and Safety ... This study is evaluating the safety, effectiveness, and how the body absorbs, distributes, and eliminates GLM101, for participants with PMM2-CDG, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9618201/

Patient reported outcomes for phosphomannomutase 2 ... Patient reported outcomes for phosphomannomutase 2 congenital disorder of glycosylation (PMM2-CDG): listening to what matters for the patients and health ...

4. glycomine.com glycomine.com/glycomine-initiates-dosing-in-a-global-randomized-placebo-controlled-phase-2b-study-of-glm101-for-the-treatment-of-pmm2-cdg/

Glycomine Initiates Dosing in a Global, Randomized ... This randomized placebo-controlled multi-center clinical trial is designed to assess the safety and efficacy of GLM101, an investigational ...

5. chiesiventures.com chiesiventures.com/glycomine-announces-first-pediatric-patient-dosed-in-phase-2-clinical-study-of-glm101-a-potential-treatment-for-pmm2-cdg/

Glycomine Announces First Pediatric Patient Dosed in ... The first pediatric patient has been dosed in a multi-center open-label Phase 2 study of GLM101, a mannose-1-phosphate replacement therapy.

6. glycomine.com glycomine.com/glm101/

GLM101: A Potential PMM2-CDG Treatment in Clinical Trials GLM101 is Glycomine's first drug from its platform and is designed to intracellularly deliver mannose-1-phosphate as a potential treatment for PMM2-CDG.

7. chiesiventures.com chiesiventures.com/glycomine-announces-encouraging-efficacy-data-from-ongoing-phase-2-clinical-study-in-pmm2-cdg/

Glycomine Announces Encouraging Efficacy Data from ... GLM101 has received Orphan Drug Designation in the U.S. and Europe and Rare Pediatric Disease Designation in the U.S. PMM2-CDG is caused by genetic mutations ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06657859

Open-Label Extension Study to Assess GLM101 in PMM2- ... 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. It ...

9. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effects-and-safety-of-glm101-for-patients-with-pmm2-cdg/

Study on the Effects and Safety of GLM101 for Patients ... This clinical trial is testing the effectiveness and safety of GLM101, administered via intravenous infusion, in treating symptoms of the ...