A Study to Assess the Efficacy and Safety of Weekly Doses of GLM101 in Participants With PMM2-CDG
- Conditions
- Phosphomannomutase 2 DeficiencyPMM2-CDG
- Interventions
- Drug: GLM101 (Part A, Double-blind)Drug: Placebo (Part A, Double-blind)Drug: GLM101 (Part B, Open-label)
- Registration Number
- NCT06892288
- Lead Sponsor
- Glycomine, Inc.
- Brief Summary
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).
- Detailed Description
This Phase 2b, multicenter, randomized, double-blind, placebo-controlled clinical study is designed to evaluate the efficacy, safety, and pharmacokinetics (PK) of GLM101 in adult, adolescent, and pediatric participants with PMM2-CDG. The study is structured into: a 4-week Screening Period, a 24-week Double-blind Treatment Period (Part A) to assess primary efficacy, a 24-week Open-label Extension Period (Part B), and a safety follow-up visit conducted 4 weeks after the last infusion. In Part A, participants will be randomly assigned to receive weekly intravenous infusions of either GLM101 at 30 mg/kg or a placebo for 24 weeks. After the end of Part A, participants will transition into Part B, a 24-week open-label extension where all participants will receive GLM101. The primary objective of the trial is to identify changes from baseline in coordination and muscle movement (ataxia) using the International Co-operative Ataxia Rating Scale (ICARS) after 24 weeks of taking GLM101 compared to a placebo in PMM2-CDG patients.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GLM101- 30 mg/kg weekly administered IV in Part A (double-blind) and Part B (open-label) GLM101 (Part A, Double-blind) - GLM101- 30 mg/kg weekly administered IV in Part A (double-blind) and Part B (open-label) GLM101 (Part B, Open-label) - Placebo weekly admin. IV in Part A (double-blind); 30 mg/kg weekly admin. IV in Part B (open-label) Placebo (Part A, Double-blind) - Placebo weekly admin. IV in Part A (double-blind); 30 mg/kg weekly admin. IV in Part B (open-label) GLM101 (Part B, Open-label) -
- Primary Outcome Measures
Name Time Method Evaluation of Ataxia Changes Using the International Cooperative Ataxia Rating Scale (ICARS) in PMM2-CDG Patients at 24 weeks At baseline and at week 24. To characterize the change from Baseline in ataxia at 24 weeks, comparing GLM101 to placebo in participants with PMM2-CDG as assessed by ICARS. The scale is scored out of 100 with 19 items and four subscales of postural and gait disturbances, limb ataxia, dysarthria, and oculomotor disorders. Higher scores indicate higher levels of impairment (Part A).
- Secondary Outcome Measures
Name Time Method Evaluation of Change from Baseline in Gross Motor Function at 24 Weeks Using the Neuromuscular Gross Motor Outcome (GRO) in PMM2-CDG Patients At baseline and at week 24. 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. The GRO is a gross neuromuscular motor outcome measure designed to assess whole body strength, motor development, and function for all levels of ability across the lifespan (Part A).
Evaluation of Change from Baseline in Ataxia at 24 Weeks Using the Scale for the Assess and Rating of Ataxia (SARA) in PMM2-CDG Patients At baseline and at week 24. To characterize the change from Baseline in ataxia at 24 weeks, comparing GLM101 to placebo in participants with PMM2-CDG as assessed by SARA. It consists of eight items of patient performance including gait, stance, sitting, speech disturbance, finger chase, nose-finger test, fast alternating hand movements, and heel-shin slide. It is scored out of 40 points with higher scores indicating higher levels of impairment (Part A).
Evaluation of Change in Global Impression of Improvement/Changes and Severity at 24 Weeks by PMM2-CDG Patients, Caregiver and Physician At baseline and at week 24. To evaluate the participant, caregiver, and physician global impression of improvement/change and severity at 24 weeks, comparing GLM101 to placebo (Part A).
Reporting of Adverse Events (AEs) in PMM2-CDG Patients at 24 weeks (Part A) At baseline and up to week 24. Reporting of Blood Pressure in PMM2-CDG Patients at 24 weeks (Part A) At baseline and up to week 24. Blood pressure will be measured in millimeters of mercury (mmHg).
Reporting of Body Temperature in PMM2-CDG Patients at 24 weeks (Part A) At baseline and up to week 24. Body Temperature will be measured in degree Celsius (°C).
Reporting of Pulse Rate in PMM2-CDG Patients at 24 weeks (Part A) At baseline and up to week 24. Pulse rate will be measured in beats per minute (bpm).
Reporting of Respiratory Rate in PMM2-CDG Patients at 24 weeks (Part A) At baseline and up to week 24. Respiratory rate will be measured in breaths per minute.
Reporting of Cardiovascular Health Using Electrocardiogram (ECG) in PMM2-CDG Patients at 24 weeks (Part A) At baseline and up to week 24. The following parameters will be evaluated: heart rate, PR, RR, QRS, QT intervals along with information on T and U-wave morphology.
Evaluation of Ataxia Changes Using the International Cooperative Ataxia Rating Scale (ICARS) in PMM2-CDG Patients from baseline to the End of the Study At baseline and at weeks 24 and 48. To evaluate the effect of GLM101 on changes in ICARS score to the end of study. The objective is to evaluate ICARS changes over 48 weeks, comparing early versus delayed GLM101 treatment, placebo-to-GLM101 transitions, and visit-wise changes in participants receiving GLM101 (Part B).
Evaluation of Changes in the Neuromuscular Gross Motor Outcome (GRO) Score in PMM2-CDG Patients from baseline to the End of the Study At baseline and at weeks 24 and 48. To evaluate the effect of GLM101 on changes in GRO score to the end of study. The objective is to evaluate changes in GRO score over 48 weeks, comparing early versus delayed GLM101 treatment, placebo-to-GLM101 transitions, and visit-wise changes in participants receiving GLM101 (Part B).
Evaluation of Changes in the Scale for the Assess and Rating of Ataxia (SARA) Score in PMM2-CDG Patients from baseline to the End of the Study At baseline and at weeks 24 and 48. To evaluate the effect of GLM101 on change in SARA score to the end of study. The objective is to evaluate changes in SARA Score over 48 weeks, comparing early versus delayed GLM101 treatment, placebo-to-GLM101 transitions, and visit-wise changes in participants receiving GLM101 (Part B).
Evaluation of Change in Global Impression of Improvement/Changes and Severity from baseline to the End of the Study by PMM2-CDG Patients, Caregiver and Physician At baseline and up to week 48. To evaluate the participant, caregiver, and physician global impression of improvement/change and severity up to 48 weeks of dosing with GLM101. Evaluation of visit-wise changes in participant, caregiver, and clinician impressions of change, severity, and improvement for overall, ataxia, and gross motor function (Part B).
Reporting of Adverse Events in PMM2-CDG Patients from Baseline to the End of the Study (Part B) At baseline and up to week 48. Reporting of Blood Pressure in PMM2-CDG Patients from Baseline to the End of the Study (Part B) At baseline and up to week 48. Blood pressure will be measured in millimeters of mercury (mmHg).
Reporting of Pulse Rate in PMM2-CDG Patients from Baseline to the End of the Study (Part B) At baseline and up to week 48. Pulse rate will be measured in beats per minute (bpm).
Reporting of Body Temperature in PMM2-CDG Patients from Baseline to the End of the Study (Part B) At baseline and up to week 48. Body Temperature will be measured in degree Celsius (°C).
Reporting of Respiratory Rate in PMM2-CDG Patients from Baseline to the End of the Study (Part B) At baseline and up to week 48. Respiratory rate will be measured in breaths per minute.
Reporting of Cardiovascular Health Changes Using Electrocardiogram (ECG) in PMM2-CDG Patients from Baseline to the End of the Study (Part B) At baseline and up to week 48. The following parameters will be evaluated: heart rate, PR, RR, QRS, QT intervals along with information on T and U-wave morphology.
Maximum Concentration (Cmax) of Mannose-1-phosphate (M1P) in PMM2-CDG Patients as Key PK Parameter over 48 weeks to the End of the Study (Part B) At Baseline and at weeks 11, 12, 20, 21, 35, 36, 44, 45. Cmax will be estimated using Blood Samples collected Pre- and Post-Infusion.
Time from dosing to the Maximum Concentration (tmax) of Mannose-1-phosphate (M1P) in PMM2-CDG Patients as Key PK Parameter over 48 weeks to the End of the Study (Part B) At Baseline and at weeks 11, 12, 20, 21, 35, 36, 44, 45. tmax will be estimated using Blood Samples collected Pre- and Post-Infusion.
Area under the concentration versus time curve (AUC) of Mannose-1-phosphate (M1P) in PMM2-CDG Patients as Key PK Parameter over 48 weeks to the End of the Study (Part B) At Baseline and at weeks 11, 12, 20, 21, 35, 36, 44, 45. AUC will be estimated using Blood Samples collected Pre- and Post-Infusion.
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Trial Locations
- Locations (13)
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
UZ Leuven, Campus Gasthuisberg
🇧🇪Leuven, Belgium
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha, Czech Republic
AP-HP Hopital Necker-Enfants Malades
🇫🇷Paris, France
Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco
🇮🇹Catania, Italy
Instytut Matki i Dziecka
🇵🇱Warszawa, Poland
Unidade Local de Saúde de Santo António
🇵🇹Porto, Portugal
Hospital Sant Joan de Déu
🇪🇸Esplugues de Llobregat (Barcelona), Spain
Great Ormond Street Hospital
🇬🇧London, United Kingdom
Birmingham Women's and Children's NHS Foundation Trust
🇬🇧Birmingham, United Kingdom