24-Week Study to Assess the PD, Safety, Tolerability, and PK of GLM101 in Adults With PMM2-CDG

Study Overview
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Brief Summary
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This is a Phase 2, randomized, open-label, 24-week treatment study to evaluate the potential pharmacodynamic (PD) activity, safety, tolerability, and pharmacokinetics (PK) of GLM101 in adult patients with a confirmed diagnosis of PMM2-CDG. The planned doses of GLM101 to be investigated are 10 and 20 mg/kg. The study will consist of a Screening Period, a 24-week (6-month) Treatment Period, and a 30-day (1-month) Follow-Up Period.

Official Title
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A Phase 2, Randomized, Open-Label, 24-Week Study to Assess the Pharmacodynamics, Safety, Tolerability, and Pharmacokinetics of Multiple Doses of GLM101 Administered Intravenously to Adult Participants With PMM2-CDG

Conditions
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Pmm2-CDG

Intervention / Treatment
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* Drug: GLM101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is a male or female, 18 to 65 years of age, inclusive, at Screening; Has been diagnosed with PMM2-CDG with genetic test confirmation; Has antithrombin III (ATIII) levels below 80%; If the participant is a female of childbearing potential, she must not be pregnant (confirmed by a negative serum pregnancy test), is using a medically accepted method of contraception (abstinence, a hormonal contraceptive in conjunction with a barrier method, double-barrier method, or use of an intrauterine device), and must agree to continue using this method for 30 days after the last infusion of GLM101; If the participant is a female of non-childbearing potential, she must be pre-pubertal, surgically sterile, or must have an ovarian dysfunction confirmed by a follicle stimulating hormone > 40 IU/L; If the participant is a sexually active male with female partners, the sexually mature, nonsterile male participant agrees to use a medically acceptable method of contraception (abstinence, the partner taking a hormonal contraceptive in conjunction with a barrier method, double-barrier method, or use by the partner of an intrauterine device) and agrees to continue using this method for 30 days after the last infusion of GLM101. Males are considered surgically sterile if they have undergone bilateral orchiectomy or vasectomy at least 3 months prior to Screening; If the participant is male, he must agree to refrain from donating sperm during the study and 30 days after the last infusion of GLM101; Is willing and able to provide informed consent/assent, directly or through his/her legally authorized representative. Exclusion Criteria: Diagnosis of congenital disorder of glycosylation (CDG) other than PMM2; Has an active infection requiring parenteral antibiotics, antivirals, or antifungals or treatment with systemic steroids within 7 days prior to Screening; Has confirmed active coronavirus disease-2019 (COVID-19) infection or tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening or check in to clinical site; Has a history of a severe allergic reaction to any drug or excipients of GLM101 (as listed in the GLM101 Investigator's Brochure); Has a known history of poor venous access; Has a history of liver transplant; Has a history of drug or alcohol use disorder within 12 months from Screening; Has had a major surgical procedure within 30 days prior to Screening; Has Screening or eligibility confirmation laboratory value(s) outside the laboratory reference range considered clinically significant and not related to PMM2-CDG; If female, has a positive serum pregnancy test during Screening; Has serology positive for hepatitis B surface antigen or hepatitis C antibody during Screening; 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 Principal Investigator's and Medical Monitor's discretion; 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 half-lives before GLM101 infusion, except for acetazolamide. Participants may be enrolled and continue treatment with acetazolamide only if they are on a stable dose for at least 30 days prior to dosing with GLM101, and the dose remains unchanged for the duration of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will assigned either 10mg/kg GLM101 or 20mg/kg GLM101 in a 1:1 ratio
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10 mg/kg GLM101<br>GLM101 IV infusions, given weekly | Drug: GLM101<br>* GLM101 IV Infusion<br>|
| Experimental: 20 mg/kg GLM101<br>GLM101 IV infusions, given weekly | Drug: GLM101<br>* GLM101 IV Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate changes in coagulation and antithrombosis factors | Changes in AT-III activity level and factor XI activity | 12 weeks and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who experience clinically significant change in pharmacodynamic activity by evaluating changes in hematology assessments | Evaluation of Pharmacodynamic activity | 12 weeks and 24 weeks | 
| Number of participants who experience clinically significant change in pharmacodynamic activity by evaluating changes in blood chemistry | Evaluation of Pharmacodynamic activity | 12 weeks and 24 weeks | 
| Number of participants with treatment-emergent adverse events assessed by severity and frequency | Safety and tolerability of multiple doses of GLM101 | 12 weeks and 24 weeks | 
| Maximum observed plasma concentration (Cmax) | Assessment of the pharmacokinetics (PK) of GLM101 | 12 weeks and 24 weeks | 
| Time to maximum observed plasma concentration (Tmax) | Assessment pharmacokinetics (PK) of GLM101 | 12 weeks and 24 weeks | 
| Area under the plasma concentration vs. time curve (AUC) | Assessment of the pharmacokinetics (PK) of GLM101 | 12 weeks and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pmm2-CDG, Pmm2