A Study to Assess the Efficacy and Safety of Weekly Doses of GLM101 in Participants With PMM2-CDG

NCT06892288 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GLM101-003
• Study Type: interventional
• Target: 50
• Locations: 10 countries
• Sites: 15

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).

Conditions

PMM2-CDG; Phosphomannomutase 2 Deficiency

Keywords

GLM101; CDG; CDG 1a; PMM2; Ataxia; GLM101-003

Outcome Measures

Primary Outcomes (1)

• Evaluation of Ataxia Changes Using the International Cooperative Ataxia Rating Scale (ICARS) in PMM2-CDG Patients at 24 weeks

  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).

  At baseline and at week 24.

Secondary Outcomes (22)

• 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.

• 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.

• 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.

• 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.

Study Arms (2)

GLM101- 30 mg/kg weekly administered IV in Part A (double-blind) and Part B (open-label)

EXPERIMENTAL

Drug: GLM101 (Part A, Double-blind); Drug: 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 COMPARATOR

Drug: Placebo (Part A, Double-blind); Drug: GLM101 (Part B, Open-label)

Interventions

Placebo (Part A, Double-blind) DRUG

IV infusions, 30 mg/kg once weekly for 24 weeks, for participants randomized to Placebo in Part A

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) DRUG

IV infusions, 30 mg/kg once weekly from week 25 to 48, to all participants

GLM101- 30 mg/kg weekly administered IV in Part A (double-blind) and Part B (open-label); Placebo weekly admin. IV in Part A (double-blind); 30 mg/kg weekly admin. IV in Part B (open-label)

GLM101 (Part A, Double-blind) DRUG

IV infusions, 30 mg/kg once weekly for 24 weeks, for participants randomized to GLM101 in Part A

GLM101- 30 mg/kg weekly administered IV in Part A (double-blind) and Part B (open-label)

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is aged ≥ 4 years old at the time of signing the consent.
• 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.
• Participant is willing and capable of completing the ICARS in its entirety without any assessment deemed as "not evaluable".
• Participant screening total ICARS score is ≥ 20 and ≤ 80 .
• Male or female participant has appropriate measures in place to prevent pregnancy:
• If the participant is a woman of childbearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile (permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy), she must not be pregnant (confirmed by a negative serum pregnancy test), is using a medically accepted method of contraception (abstinence, a hormonal contraceptive associated with inhibition of ovulation in conjunction with a barrier method, or use of an intrauterine device), and must agree to continue using this method for 50 days after the last infusion. Note: sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception.
• If the participant is a female of non-childbearing potential, she must be premenarchal, surgically sterile, or must have an ovarian dysfunction confirmed by a follicle stimulating hormone \> 40 IU/ L (or higher per local institutional guidelines) and absence of menses for 12 months after last menstrual bleeding without an alternative medical cause.
• If the participant is a sexually active male with female partners, the participant agrees to use a medically acceptable method of contraception (abstinence, the partner taking a hormonal contraceptive in conjunction with male participant using male condom, or use by the partner of an intrauterine device with a male participant using male condom) and agrees to continue using this method for 50 days after the last infusion.
• If the participant is male, he must agree to refrain from donating sperm during the study and 50 days after the last infusion.
• The participant is willing and able to provide informed consent/assent, directly or through his/her legally authorized representative.
• The participant has a caregiver who is willing and able to complete questionnaires and provide informed consent.

You may not qualify if:

• Has uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric or other significant disease based on the investigator judgment.
• 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 biallelic variants and the defined CDG enzyme activity consistent with a diagnosis of the CDG other than PMM2 CDG.
• Has a history of liver transplant.
• Has an active infection requiring parenteral antibiotics, antivirals, antifungals or treatment with systemic steroids within 7 days prior to screening.
• 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 or an upcoming planned major surgery.
• Previous history of GLM101 administration.
• 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 (whichever is longer) before enrollment.
• Have consumed products or supplements containing mannose or biotin within 2 weeks prior to screening.
• Elevated liver function tests: ALT or AST \> 3 × ULN OR total bilirubin \> 2 × ULN or international normalized ratio (INR) \> 1.5 (if no anti-coagulation treatment) or INR \> 4 (if participant on anti-coagulation treatment).
• Has screening laboratory value(s) considered clinically significant and not related to PMM2-CDG based on the investigator judgment.
• Has serology positive for hepatitis B surface antigen or hepatitis C antibody during screening.
• Has a QT interval by Fridericia (QTcF) ≥ 450 ms, or other electrocardiogram abnormalities judged as clinically significant by the investigator.
• 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.
• Participant weighs above 120 kg.

Sponsors & Collaborators

• Glycomine, Inc.: lead

Study Sites (15)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

UZ Leuven, Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Vseobecna fakultni nemocnice v Praze

Prague, 2, 128 0, Czechia

Location

AP-HP Hopital Necker-Enfants Malades

Paris, 75015, France

Location

Universitaetsklinikum Muenster

Münster, 48149, Germany

Location

Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco

Catania, 95124, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

Location

Instytut Matki i Dziecka

Warsaw, 01-211, Poland

Location

Unidade Local de Saúde de Santo António

Porto, 4099-001, Portugal

Location

Hospital Sant Joan de Déu

Esplugues de Llobregat, 08950, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, B4 6NH, United Kingdom

Location

MeSH Terms

Conditions

Congenital disorder of glycosylation type 1A; Ataxia

Interventions

Double-Blind Method

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Chief Medical Officer

  Glycomine, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to receive either GLM101 or placebo (Part A) and subsequently all participants will receive GLM101 (Part B).

Study Record Dates

• First Submitted: February 6, 2025
• First Posted: March 24, 2025
• Study Start: July 9, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

BE (1); ES (2); PT (1); DE (1); US (4); IT (2); CZ (1); GB (1); PL (1); FR (1)