A Study to Assess the Efficacy and Safety of Weekly Doses of GLM101 in Participants with PMM2-CDG

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glycomine Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

9 Jul 2025 → ongoing

Decision date (initial)

2025-06-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Glycomine, Inc

External identifiers

EU CT number

2024-520109-37-00

WHO UTN

U1111-1317-9511

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic, Efficacy

To characterize the change from Baseline in ataxia at 24 weeks, comparing GLM101 to placebo in participants with PMM2-CDG as assessed by ICARS

Secondary objectives 10

1. 1.To characterize the change from Baseline in ataxia at 24 weeks, comparing GLM101 to placebo in participants with PMM2-CDG as assessed by SARA
2. 2. To characterize the change from Baseline in gross motor function at 24 weeks, comparing GLM101 to placebo in participants with PMM2-CDG as assessed by GRO
3. 3. To evaluate the participant, caregiver, and physician global impression of improvement/change and severity at 24 weeks, comparing GLM101 to placebo
4. 4.To assess the safety and tolerability of multiple doses of GLM101 at 24 weeks compared with placebo
5. 5.To evaluate the effect of GLM101 on changes in ICARS score to the end of study
6. 6.To evaluate the effect of GLM101 on changes in GRO score to the end of study
7. 7.To evaluate the effect of GLM101 on change in SARA score to the end of study
8. 8.To evaluate the participant, caregiver, and physician global impression of improvement/change and severity up to 48 weeks of dosing with GLM101
9. 9.To assess the safety and tolerability of multiple doses of GLM101 from Baseline through 48 weeks of dosing
10. 10.To assess the PK of GLM101 in participants with PMM2-CDG up to the end of the study

Conditions and MedDRA coding

PMM2-CDG

Regulatory references

Scientific advice from competent authorities

Medicines And Healthcare Products Regulatory Agency, Spanish Agency Of Medicines And Medical Devices, European Medicines Agency, Federal Agency For Medicines And Health Products

EMA paediatric investigation plan (PIP)

EMEA-003460-PIP01-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1.Participant is aged ≥ 4 years old at the time of signing the consent
2. 2.Participant with molecular 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 biallelic variants and PMM2 enzyme activity consistent with a diagnosis of PMM2-CDG. Diagnosis with laboratory report(s) on file is required.
3. 3.Participant is willing and capable of completing the ICARS in its entirety without any assessment deemed as “not evaluable”.
4. 4.Participant screening total ICARS score is ≥ 20 and ≤ 80
5. 5.Male or female participant has appropriate measures in place to prevent pregnancy
6. 6.If the participant is male, he must agree to refrain from donating sperm during the study and 50 days after the last infusion
7. 7.The participant is willing and able to provide informed consent/assent, directly or through his/her legally authorized representative (LAR)
8. 8.The participant has a caregiver who is willing and able to complete questionnaires and provide the informed consent

Exclusion criteria 20

1. 1.Has uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric or other significant disease based on the investigator judgment
2. 10.Elevated liver function tests: 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)
3. 11. Has screening laboratory value(s) considered clinically significant and not related to PMM2-CDG based on the investigator judgment
4. 12. Has serology positive for hepatitis B surface antigen or hepatitis C antibody during screening
5. 13.Has a QT interval by Fridericia (QTcF) ≥ 450 ms, or other electrocardiogram (ECG) abnormalities judged as clinically significant by the investigator
6. 14.Has history or presence, upon clinical evaluation, of any illness that might impact the safety of GLM101 infusion or evaluability of drug effect based on the investigator’s and Sponsor’s Medical Monitor’s discretion
7. 15.Participant weighs above 120 kg
8. 16.Participant has a known or suspected hypersensitivity to GLM101 or any components of the formulation used
9. 17.Any other reason for which, in the investigator’s opinion, makes the participant unsuitable for study participation
10. 2.Diagnosis of 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 biallelic variants and the defined CDG enzyme activity consistent with a diagnosis of the CDG other than PMM2 CDG
11. 3.Has a history of liver transplant
12. 4.Has an active infection requiring parenteral antibiotics, antivirals, antifungals or treatment with systemic steroids within 7 days prior to screening
13. 5.Has a history of drug or alcohol use disorder within 12 months prior to screening
14. 6.Has had a major surgical procedure within 30 days prior to screening or an upcoming planned major surgery
15. 7.Previous history of GLM101 administration
16. 8.Is currently participating in another interventional clinical study or has completed another clinical study with an investigational drug or device within 30 days or 5 halflives (whichever is longer) before enrollment.
17. 9.Have consumed products or supplements containing mannose or biotin within 2 weeks prior to screening
18. 18.If female, must not be breastfeeding
19. 19.Estimated glomerular filtration rate (eGFR) <45 mL/min/ 1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for participants ≥ 18 years or Schwartz equation for participants <18 years of age at screening
20. 20.Persons who have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline in ICARS at 24 weeks

Secondary endpoints 16

1. 1. Change from Baseline in GRO at 24 weeks
2. 2.Change from Baseline in SARA at 24 weeks
3. 3.Changes from Baseline in participants and caregiver global impression of change (overall, ataxia, and gross motor function) and global impression of severity (ataxia and gross motor function) and clinician global impression of improvement (overall), global impression of change (ataxia and gross motor function), and global impression of severity (ataxia and gross motor function) at 24 weeks
4. 4.Evaluation of safety throughout 24 weeks through the collection of safety parameters: o AEs, AESIs (including IARs), SAEs, deaths, and discontinuations due to AEs o Clinical safety laboratory tests o Immunogenicity o ECG, vital signs, and PE findings
5. 5.Change from Baseline to Week 24 compared to the change from Week 24 to Week 48 in ICARS for participants who switched from placebo to GLM101 treatment at Week 24
6. 6.Change from Baseline in ICARS for participants randomized to placebo in Part A and who switched to active treatment in Part B compared to change from Baseline in ICARS in participants who were randomized to GLM101 from the beginning of the study in order to compare the GLM101 effect between the early start group and the delayed start group
7. 7. Visit-wise changes from Baseline in ICARS up to 48 weeks of GLM101 treatment in participants who were initially randomized to GLM101
8. 8. Change from Baseline to Week 24 compared to the change from Week 24 to Week 48 in GRO for participants who switched from placebo to GLM101 treatment at Week 24
9. 9. Change from Baseline in GRO for participants randomized to placebo in Part A and who switched to active treatment in Part B compared to change from Baseline in GRO in participants who were randomized to GLM101 from the beginning of the study in order to compare the GLM101 effect between the early start group and the delayed start group
10. 10. Visit-wise changes from Baseline in GRO up to 48 weeks of GLM101 treatment in participants who were initially randomized to GLM101
11. 11. Change from Baseline to Week 24 compared to the change from Week 24 to Week 48 in SARA for participants who switched from placebo to GLM101 treatment at Week 24
12. 12. Change from Baseline in SARA for participants randomized to placebo in Part A and who switched to active treatment in Part B compared to change from Baseline in SARA in participants who were randomized to GLM101 from the beginning of the study in order to compare the GLM101 effect between the early start group and the delayed start group
13. 13. Visit-wise changes from Baseline in SARA up to 48 weeks of GLM101 treatment in participants initially randomized to GLM101
14. 14.Visit-wise changes in participants and caregiver global impression of change (overall, ataxia and gross motor function) and global impression of severity (ataxia and gross motor function) and clinician global impression of improvement (overall), global impression of change (ataxia and gross motor function), and global impression of severity (ataxia and gross motor function) up to 48 weeks of dosing
15. 15.Evaluation of safety through 48 weeks of GLM101 treatment through the collection of safety parameters: o AEs, AESIs (including IARs), SAEs, deaths, and discontinuations due to AEs o Clinical safety laboratory tests o Immunogenicity o ECG, vital signs, and PE findings
16. 16.Concentrations of total M1P to estimate PK parameters including Cmax, Clast, tmax, tlast, t1/2, AUC0-last, AUC0-∞, AUC0-tau, CL, Vz, Vss, and λz

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glycomine Inc.

Sponsor organisation

Glycomine Inc.

Address

733 Industrial Road

City

San Carlos

Postcode

94070-3310

Country

United States

Scientific contact point

Organisation

Glycomine Inc.

Contact name

Rose Marino

Public contact point

Organisation

Glycomine Inc.

Contact name

Rose Marino

Third parties 3

Locations

8 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 111 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications