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 and Adolescent Participants with PMM2-CDG
- Conditions
- Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]PMM2-CDGMedDRA version: 20.0Level: LLTClassification code: 10027426Term: Metabolic disorder NOS Class: 10027433
- Registration Number
- CTIS2024-513119-29-00
- Lead Sponsor
- Glycomine Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 19
Is male or female, 18 to 65 years of age, inclusive, at Screening (Cohorts 1-3) or 12- 17 years of age, inclusive, at Screening (Cohort 4), Molecularly confirmed 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 bi-allelic variants AND phosphomannomutase-2 (PMM2) enzyme activity consistent with a diagnosis of PMM2-CDG. Historical diagnosis with lab report(s) on file is permitted, Has antithrombin III (ATIII) activity levels below 65%, 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 (FSH) >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
Diagnosis of congenital disorder of glycosylation (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 bi-allelic variants AND the defined CDG enzyme activity consistent with a diagnosis of the CDG other than PMM2 CDG, 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 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 halflives 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, Weight exceeds 75 kg, 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) or tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening or check in to the clinical site, ALT or AST >3× ULN and (total bilirubin >2× ULN or INR >1.5), 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 prior to Screening, Has had a major surgical procedure within 30 days prior to Screening
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate changes in coagulation and antithrombosis factors in participants with PMM2-CDG after 12 and 24 weeks of dosing;Secondary Objective: To evaluate the potential PD activity of GLM101 in participants with PMM2- CDG after 12 and 24 weeks of dosing, To assess the 12- and 24-week safety and tolerability of multiple doses of GLM101 in cohorts of participants with PMM2- CDG, To assess the PK of GLM101 in participants with PMM2-CDG after 12 and 24 weeks of dosing;Primary end point(s): Changes in ATIII activity level and change in Factor XI activity
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Evaluate the potential PD activity through clinical laboratory tests;Secondary end point(s):Evaluate the safety through AEs, SAEs, deaths, and discontinuations due to AEs, clinical laboratory tests (hematology, chemistry, and urinalysis), ECG, vital signs, and PE findings;Secondary end point(s):Concentrations of total M1P to estimate PK parameters including Cmax, Clast, tmax, tlast, t1/2, AUC0-last, AUC0-8, AUC0-tau, %AUCex, CL, Vz, Vss, and ?z