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

Pmm2-CDG Clinical Trial

Official title:

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, Adolescent, and Pediatric Participants With PMM2-CDG

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05549219
• Other study ID #: GLM101-002
• Status: Recruiting
• Phase: Phase 2
• Start date: November 29, 2022
• Est. completion date: April 2025

Study information

• Verified date: March 2024
• Source: Glycomine, Inc.
• Contact: Director Clinical Operations
• Phone: 650-264-7560
• Email: info[@]glycomine.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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, adolescent, and pediatric, patients with a confirmed diagnosis of PMM2-CDG. The planned doses of GLM101 to be investigated are 10, 20 and 30 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 65 Years

Eligibility

Inclusion Criteria:

• Is a male or female, 18 to 65 years of age, inclusive, at Screening; 12-17 years of age inclusive at Screening or 2-11 years of age, inclusive at Screening
• Has been diagnosed with PMM2-CDG with genetic test confirmation;
• 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) 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 >3x ULN and total bilirubin >2x ULN or INR >1.5 (abnormal biological values of liver function)
• 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 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.
• Weight exceeds 75 kg

Related Conditions & MeSH terms

• Congenital Disorders of Glycosylation
• Pmm2-CDG

Intervention

Drug:
• GLM101
GLM101 IV Infusion

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Spain	Hospital Sant Joan de Déu	Barcelona
United States	University of Minnesota	Minneapolis	Minnesota
United States	Mayo Clinic	Rochester	Minnesota
United States	Clinical Research of West Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Glycomine, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate changes in coagulation and antithrombosis factors	Changes in AT-III activity level and factor XI activity	12 weeks and 24 weeks
Primary	Evaluate changes from baseline in ataxia	Changes in ICARS (International Co-operative Ataxia Rating Scale)	12 weeks and 24 weeks
Secondary	Significant change in pharmacodynamic activity	Evaluation of Pharmacodynamic activity in blood biomarkers (glycomics, glycoproteomics, and transferrin isoform ratios)	12 weeks and 24 weeks
Secondary	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
Secondary	Maximum observed plasma concentration (Cmax)	Assessment of the pharmacokinetics (PK) of GLM101	12 weeks and 24 weeks
Secondary	Time to maximum observed plasma concentration (Tmax)	Assessment pharmacokinetics (PK) of GLM101	12 weeks and 24 weeks
Secondary	Area under the plasma concentration vs. time curve (AUC)	Assessment of the pharmacokinetics (PK) of GLM101	12 weeks and 24 weeks