A Long-Term Study with GLM101 in Patients with PMM2-CDG

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glycomine Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

27 Sep 2024 → ongoing

Decision date (initial)

2026-05-12

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Glycomine Inc.

External identifiers

EU CT number

2024-512171-12-00

ClinicalTrials.gov

NCT06657859

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

• To examine the safety of GLM101 in PMM2-CDG patients who previously received GLM101

Secondary objectives 2

1. • To examine changes in coordination and balance (ataxia)
2. • To measure the sugar delivered by GLM101 in participants with PMM2-CDG

Conditions and MedDRA coding

PMM2-CDG

Regulatory references

Scientific advice from competent authorities

Federal Agency For Medicines And Health Products, European Medicines Agency, Medicines And Healthcare Products Regulatory Agency, Spanish Agency For Medicines And Health Products

EMA paediatric investigation plan (PIP)

EMEA-003460-PIP01-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Is willing and able to provide informed consent/assent, directly or through a legally authorized representative
2. Has successfully completed the Treatment Period with GLM101 in a previous clinical study.
3. At least 2 years of age inclusive, at the time of signing the informed consent form (ICF).
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 including from a prior parent trial is permitted;
5. 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.
6. Male or female participant has appropriate measures in place to prevent pregnancy: 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.
7. Male or female participant has appropriate measures in place to prevent pregnancy: 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.
8. 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
9. Is willing and able to comply with this protocol.

Exclusion criteria 19

1. 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
2. Has a history of drug or alcohol use disorder within the 12 months prior to Screening
3. 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
4. Has laboratory value(s) outside the laboratory reference range considered clinically significant and not related to PMM2-CDG
5. If female, has a positive serum pregnancy test during Screening.
6. 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;
7. Has a QTc ≥ 450 ms, or other clinically significant ECG abnormalities;
8. Has uncontrolled cardiovascular, hepatic, pulmonary, gastro-intestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric or other significant disease;
9. Weight exceeds 120 kg.
10. Participant is unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, other study procedures, and study restrictions.
11. If female, and breastfeeding
12. 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
13. Must not have a hypersentivity to GLM101 or anti-histamine pre-medication.
14. Has a history of a severe allergic reaction to any drug or excipients of GLM101 (as listed in the GLM101 IB);
15. 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
16. 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;
17. 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;
18. Has a history of liver transplant
19. Persons who have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities;

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Collection of the safety information from the collection of Side effects (or Adverse Events), deaths, and stopping the study due to side effects; Tests from blood and urine (hematology, chemistry, and urinalysis) (compared to before treatment with GLM101); ECG (heart tracings), vital signs (blood pressure, heart rate, and body temperature), and physical exam changes (compared to before treatment with GLM101)

Secondary endpoints 2

1. Changes in International Co-operative Ataxia Rating Scale, ICARS (evaluated every 3-6 months, compared to before treatment with GLM101)
2. The amount of Mannose-1-Phosphate (the sugar contained in a lipid bubble, which together make up GLM101) in blood (evaluated at Month 6)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glycomine Inc.

Sponsor organisation

Glycomine Inc.

Address

733 Industrial Road

City

San Carlos

Postcode

94070-3310

Country

United States

Scientific contact point

Organisation

Glycomine Inc.

Contact name

Rose Marino

Public contact point

Organisation

Glycomine Inc.

Contact name

Rose Marino

Third parties 4

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications