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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glycomine Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

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

Trial duration

2 Dec 2022 → 18 Nov 2025

Decision date (initial)

2024-04-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Glycomine, Inc.

External identifiers

EU CT number

2024-513119-29-00

EudraCT number

2022-000565-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Pharmacokinetic, Pharmacodynamic

To characterize the changes from baseline in ataxia after 12 and 24 weeks of dosing with GLM101 in participants with PMM2-CDG

Secondary objectives 2

1. To assess the 12- and 24-week safety and tolerability of multiple doses of GLM101 in cohorts of participants with PMM2- CDG
2. To assess the PK of GLM101 in participants with PMM2-CDG over 24 weeks of dosing

Conditions and MedDRA coding

PMM2-CDG

Regulatory references

Scientific advice from competent authorities

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

EMA paediatric investigation plan (PIP)

EMEA-003460-PIP01-23

Plan to share IPD

No

IPD plan description

To be decided.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Is male or female, 18 to 65 years of age, inclusive, at Screening (Cohorts 1-3, 7), 12-17 years of age, inclusive, at Screening (Cohort 4) or 2-11 years of age, inclusive, at Screening (Cohorts 5 and 6)
2. 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
3. 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)) 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 twith 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
4. 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
5. 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 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
6. If the participant is male, he must agree to refrain from donating sperm during the study and 60 days after the last infusion of GLM101
7. Is willing and able to provide informed consent/assent, directly or through his/her legally authorized representative

Exclusion criteria 18

1. 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.
2. Has an active infection requiring parenteral antibiotics, antivirals, or antifungals or treatment with systemic steroids within 7 days prior to Screening
3. 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
4. ALT or AST >3× ULN OR total bilirubin >2× ULN or INR >1.5
5. Has a history of a severe allergic reaction to any drug or excipients of GLM101 (as listed in the GLM101 Investigator’s Brochure)
6. Has a known history of poor venous access
7. Has a history of liver transplant
8. Has a history of drug or alcohol use disorder within 12 months prior to Screening
9. Has had a major surgical procedure within 30 days prior to Screening
10. Has Screening or eligibility confirmation laboratory value(s) outside the laboratory reference range considered clinically significant and not related to PMM2-CDG
11. If female, has a positive serum pregnancy test during Screening
12. If female, must not be breastfeeding
13. Has serology positive for hepatitis B surface antigen or hepatitis C antibody during Screening;
14. 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
15. Has a QTc ≥ 450 ms, or other clinically significant ECG abnormalities
16. Has uncontrolled cardiovascular, hepatic, pulmonary, gastro-intestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric or other significant disease
17. 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
18. Weight exceeds 75 kg

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in ICARS

Secondary endpoints 2

1. Evaluation of safety through the collection of safety parameters: AEs, AESIs (including Infusion-Associated Reactions), SAEs, deaths, and discontinuations due to AEs, clinical laboratory tests (hematology, chemistry, and urinalysis), ECG, vital signs, and PE findings
2. Concentrations of total M1P to estimate PK parameters including Cmax, Clast, tmax, tlast, t1/2, AUC0-last, AUC0-∞, AUC0-tau, %AUCex, CL, Vz, Vss, and λz

Investigational products

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

Test 1

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 5

Locations

1 EU/EEA country · 1 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 13 files

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

Application history

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