Open-Label Extension Study to Assess GLM101 in PMM2-CDG Patients

NCT06657859 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 1 other identifier: GLM101-007
• Study Type: interventional
• Target: 90
• Locations: 8 countries
• Sites: 15

Brief Summary

The goal of this clinical trial is to provide continued access to GLM101 to treat PMM2-CDG in people who have previously received GLM101 in other trials and learn about the long term effect of GLM101. Participants will complete weekly infusions of GLM101 at the same dose level received in previous trials.

Conditions

Pmm2-CDG; Phosphomannomutase 2 Deficiency

Keywords

GLM101; Pmm2; CDG; CDG 1a

Outcome Measures

Primary Outcomes (1)

• Evaluate long-term safety

  Number of participants with treatment related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  From enrollment to end of treatment up to 4 years

Secondary Outcomes (4)

• Evaluate changes in ataxia using International Cooperative Ataxia Rating Scale (ICARS)

  From enrollment, at 3 months, 6 months and annually to end of treatment up to 4 years

• Maximum observed plasma concentration (Cmax)

  From enrollment to end of treatment up to 4 years

• Time to maximum observed plasma concentration (Tmax)

  From enrollment to end of treatment up to 4 years

• Area under the plasma concentration vs. time curve (AUC)

  From enrollment to end of treatment up to 4 years

Study Arms (1)

30 mg/kg GLM101

EXPERIMENTAL

GLM101 IV infusions, given weekly

Drug: GLM101

Interventions

GLM101 DRUG

GLM101 IV infusion

30 mg/kg GLM101

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Is willing and able to provide informed consent/assent, directly or through a legally authorized representative.
• Has successfully completed the Treatment Period with GLM101 in a previous clinical study.
• At least 2 years of age, at the time of signing the informed consent form (ICF).
• 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 including from a prior parent trial is permitted;
• Male or female participant has appropriate measures in place to prevent pregnancy:
• If the participant is a female of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile (permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy)) or becomes of childbearing potential during the study, 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 of GLM101. Note: True abstinence: 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 (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• 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 and absence of menses for 12 months without an alternative medical cause.
• If the participant is a sexually active (or becomes sexually active during the study) 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 male condom, or use by the partner of an intrauterine device with a male condom) and agrees to continue using this method for 50 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 50 days after the last infusion of GLM101.
• Is willing and able to comply with this protocol.

You may not qualify if:

• Participants who meet any of the following criteria will be excluded from participation in the study:
• Has any other condition that would, in the opinion of the Investigator, potentially compromise the safety or compliance of the participant or preclude the participant's successful completion of the study.
• 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.
• If not enrolling directly from a parent study (i.e., more than 28 days from Final Treatment visit in a parent study to date of consent), has an active infection requiring parenteral antibiotics, antivirals, or antifungals or treatment with systemic steroids within 7 days prior to Screening;
• ALT or AST \>3× ULN OR total bilirubin \>2× ULN or INR \>1.5 (if no anti-coagulation treatment) or INR \> 4 (if participant on anti-coagulation treatment) considered clinically significant;
• Has a history of liver transplant;
• Has a history of drug or alcohol use disorder within the 12 months prior to Screening;
• If not enrolling directly from a parent study (i.e., if more than 28 days from Final Treatment visit in a parent study to date of consent), has had a major surgical procedure within 30 days prior to Screening;
• Has 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.
• If female, and breastfeeding.
• Is currently participating in another interventional clinical study or has completed another clinical study with an investigational drug or device (other than GLM101) within 30 days or 5 half-lives before GLM101 infusion.
• Has a hypersensitivity to anti-histamine pre-medication.
• Has a history of a severe allergic reaction to any drug or excipients of GLM101 (as listed in the GLM101 IB);
• If not enrolling directly from a parent study (i.e., if more than 28 days from Final Treatment visit in a parent study to date of consent), has serology positive for hepatitis B surface antigen or hepatitis C antibody during Screening;

Sponsors & Collaborators

• Glycomine, Inc.: lead

Study Sites (15)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

The Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

The Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 08, Czechia

Location

AP-HP Hopital Universitaire Necker-Enfants Malades

Paris, 75015, France

Location

Universitaetsklinikum Münster

Münster, 48149, Germany

Location

Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico

Catania, 95124, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

Location

Unidade Local de Saúde de Santo António, E.P.E

Porto, 4099-001, Portugal

Location

Hospital Sant Joan de Déu

Esplugues de Llobregat, 08950, Spain

Location

Hospital Universitario 12 de Octubre - Unidad Pediatrica de Investigacion y Ensayos Clinicos (UPIC)

Madrid, 28041, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Great Ormond Street Hospital for Children

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Congenital disorder of glycosylation type 1A

Study Officials

• Chief Medical Officer

  Glycomine, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label extension study.

Study Record Dates

• First Submitted: October 22, 2024
• First Posted: October 26, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: July 28, 2026

Record last verified: 2026-07

Locations

ES (3); GB (2); FR (1); US (4); IT (2); PT (1); CZ (1); DE (1)