ALFA-D-MANNOSE 1-PHOSPHATE DIPOTASSIUM for PMM2-CDG | Congenital disorder of glycosylation

Inclusion criteria

• {"criterion_text":"- 1.Participant is aged ≥ 4 years old at the time of signing the consent"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 3.Participant is willing and capable of completing the ICARS in its entirety without any assessment deemed as “not evaluable”."}
• {"criterion_text":"- 4.Participant screening total ICARS score is ≥ 20 and ≤ 80"}
• {"criterion_text":"- 5.Male or female participant has appropriate measures in place to prevent pregnancy"}
• {"criterion_text":"- 6.If the participant is male, he must agree to refrain from donating sperm during the study and 50 days after the last infusion"}
• {"criterion_text":"- 7.The participant is willing and able to provide informed consent/assent, directly or through his/her legally authorized representative (LAR)"}
• {"criterion_text":"- 8.The participant has a caregiver who is willing and able to complete questionnaires and provide the informed consent"}

Exclusion criteria

• {"criterion_text":"- 1.Has uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric or other significant disease based on the investigator judgment"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 3.Has a history of liver transplant"}
• {"criterion_text":"- 4.Has an active infection requiring parenteral antibiotics, antivirals, antifungals or treatment with systemic steroids within 7 days prior to screening"}
• {"criterion_text":"- 5.Has a history of drug or alcohol use disorder within 12 months prior to screening"}
• {"criterion_text":"- 6.Has had a major surgical procedure within 30 days prior to screening or an upcoming planned major surgery"}
• {"criterion_text":"- 7.Previous history of GLM101 administration"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 9.Have consumed products or supplements containing mannose or biotin within 2 weeks prior to screening"}
• {"criterion_text":"- 18.If female, must not be breastfeeding"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 20.Persons who have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities"}
• {"criterion_text":"- 11. Has screening laboratory value(s) considered clinically significant and not related to PMM2-CDG based on the investigator judgment"}
• {"criterion_text":"- 12. Has serology positive for hepatitis B surface antigen or hepatitis C antibody during screening"}
• {"criterion_text":"- 13.Has a QT interval by Fridericia (QTcF) ≥ 450 ms, or other electrocardiogram (ECG) abnormalities judged as clinically significant by the investigator"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 15.Participant weighs above 120 kg"}
• {"criterion_text":"- 16.Participant has a known or suspected hypersensitivity to GLM101 or any components of the formulation used"}
• {"criterion_text":"- 17.Any other reason for which, in the investigator’s opinion, makes the participant unsuitable for study participation"}

Primary endpoints

• {"endpoint_text":"- Change from Baseline in ICARS at 24 weeks","definition_or_measurement_approach":"Change from Baseline in ataxia at 24 weeks as assessed by the International Cooperative Ataxia Rating Scale (ICARS)."}

Secondary endpoints

• {"endpoint_text":"- 1. Change from Baseline in GRO at 24 weeks","definition_or_measurement_approach":"Change from Baseline in gross motor function at 24 weeks as assessed by GRO."}
• {"endpoint_text":"- 2.Change from Baseline in SARA at 24 weeks","definition_or_measurement_approach":"Change from Baseline in ataxia at 24 weeks as assessed by SARA."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Participant, caregiver and clinician global impression scales (improvement/change and severity) at 24 weeks comparing GLM101 to placebo."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Safety monitoring via collection of adverse events (AEs), adverse events of special interest (AESIs, including infusion reactions), serious adverse events (SAEs), deaths, discontinuations for AEs, clinical safety labs, immunogenicity assessments, ECGs, vital signs and physical exam findings over 24 weeks."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Comparison of ICARS change baseline->Week24 vs Week24->Week48 in participants who switch from placebo to active at Week24 (delayed-start analysis)."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Comparison of ICARS changes between early-start (GLM101 from baseline) and delayed-start (placebo then GLM101) groups to assess treatment effect timing."}
• {"endpoint_text":"- 7. Visit-wise changes from Baseline in ICARS up to 48 weeks of GLM101 treatment in participants who were initially randomized to GLM101","definition_or_measurement_approach":"Visit-wise (per scheduled visit) ICARS changes from baseline up to 48 weeks in participants randomized initially to GLM101."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Compare GRO change baseline->Week24 vs Week24->Week48 in participants who switched from placebo to GLM101 at Week24."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Compare GRO changes between early-start and delayed-start groups."}
• {"endpoint_text":"- 10. Visit-wise changes from Baseline in GRO up to 48 weeks of GLM101 treatment in participants who were initially randomized to GLM101","definition_or_measurement_approach":"Visit-wise GRO changes from baseline up to 48 weeks in participants initially randomized to GLM101."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Compare SARA change baseline->Week24 vs Week24->Week48 in participants who switched from placebo to GLM101 at Week24."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Compare SARA changes between early-start and delayed-start groups."}
• {"endpoint_text":"- 13. Visit-wise changes from Baseline in SARA up to 48 weeks of GLM101 treatment in participants initially randomized to GLM101","definition_or_measurement_approach":"Visit-wise SARA changes from baseline up to 48 weeks in participants initially randomized to GLM101."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Visit-wise assessments of participant, caregiver and clinician global impression scales (change/improvement and severity) up to 48 weeks."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Safety monitoring via AEs, AESIs, SAEs, deaths, discontinuations, clinical labs, immunogenicity, ECG, vitals and PE findings over 48 weeks."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Pharmacokinetic analysis measuring total M1P concentrations to estimate PK parameters (Cmax, Clast, tmax, tlast, t1/2, AUCs, CL, Vz, Vss, λz)."}

Italy

Earliest CTIS Part Ii Submission Date

11-03-2025

Latest Decision Or Authorization Date

27-01-2026

Processing Time Days

322

Number Of Sites

2

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

28-03-2025

Latest Decision Or Authorization Date

30-01-2026

Processing Time Days

309

Number Of Sites

1

Number Of Participants

8

Belgium

Earliest CTIS Part Ii Submission Date

12-05-2025

Latest Decision Or Authorization Date

27-01-2026

Processing Time Days

261

Number Of Sites

1

Number Of Participants

4

Portugal

Earliest CTIS Part Ii Submission Date

11-03-2025

Latest Decision Or Authorization Date

27-01-2026

Processing Time Days

322

Number Of Sites

1

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

20-05-2025

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

254

Number Of Sites

2

Number Of Participants

9

Germany

Earliest CTIS Part Ii Submission Date

05-05-2025

Latest Decision Or Authorization Date

27-01-2026

Processing Time Days

268

Number Of Sites

1

Number Of Participants

5

Czechia

Earliest CTIS Part Ii Submission Date

13-05-2025

Latest Decision Or Authorization Date

05-02-2026

Processing Time Days

269

Number Of Sites

1

Number Of Participants

7

Poland

Earliest CTIS Part Ii Submission Date

07-05-2025

Latest Decision Or Authorization Date

30-03-2026

Processing Time Days

328

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

Glycomine Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Fisher Clinical Services GmbH

Responsibilities

code: 14

Name

Medpace Finland Oy

Responsibilities

codes: 1,12,13,14,15,2,3,4,5,6,7,8; value: concierge services, ECG

Third parties

• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"codes: 1,12,13,14,15,2,3,4,5,6,7,8; value: concierge services, ECG","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pentara Corp.","duties_or_roles":"code: 10","organisation_type":"Pharmaceutical company"}