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

Официальное название

A Phase 2, Open-Label Extension Study to Assess the Safety and Efficacy of GLM101 Administered Intravenously to Participants With PMM2-CDG

Обзор

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.

Подробное описание

This is a phase 2 open-label clinical study of GLM101 in patients with PMM2-CDG who have previously participated in a study of GLM101. This study is designed to monitor long-term safety and treatment effect of GLM101 and provide continued access to study treatment. Participants will receive 30 mg/kg. Dose levels may be adjusted to lower doses or higher doses based on available data that demonstrates a change to be safe and favorable. Among other assessments, participants will be asked to complete questionnaires to evaluate changes in ataxia and quality of life.

Вмешательства

• Препарат GLM101
  GLM101 IV infusion

Первичные конечные точки

• Evaluate long-term safety [Срок оценки: From enrollment to end of treatment up to 4 years]

Вторичные конечные точки (4)

• Evaluate changes in ataxia using International Cooperative Ataxia Rating Scale (ICARS) [Срок оценки: From enrollment, at 3 months, 6 months and annually to end of treatment up to 4 years]
• Maximum observed plasma concentration (Cmax) [Срок оценки: From enrollment to end of treatment up to 4 years]
• Time to maximum observed plasma concentration (Tmax) [Срок оценки: From enrollment to end of treatment up to 4 years]
• Area under the plasma concentration vs. time curve (AUC) [Срок оценки: From enrollment to end of treatment up to 4 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

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;
• Has a QTc ≥ 450 ms, or other clinically significant ECG abnormalities;
• Has uncontrolled cardiovascular, hepatic, pulmonary, gastro-intestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric or other significant disease;
• Weight exceeds 120 kg.
• Persons who have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
• Participant is unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, other study procedures, and study restrictions.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 4 центра

• University of Minnesota — Minneapolis
• The Icahn School of Medicine at Mount Sinai — New York
• The Children's Hospital of Philadelphia (CHOP) — Philadelphia
• Seattle Children's Hospital — Seattle

Испания · 3 центра

• Hospital Sant Joan de Déu — Esplugues de Llobregat
• Hospital Universitario 12 de Octubre - Unidad Pediatrica de Investigacion y Ensayos Clinic — Madrid
• Hospital Universitario 12 de Octubre — Madrid

Италия · 2 центра

• Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero — Catania
• Azienda Ospedaliero Universitaria Pisana — Pisa

Великобритания · 2 центра

• Birmingham Children's Hospital — Birmingham
• Great Ormond Street Hospital for Children — London

Чехия · 1 центр

• Vseobecna fakultni nemocnice v Praze — Prague

Франция · 1 центр

• AP-HP Hopital Universitaire Necker-Enfants Malades — Paris

Германия · 1 центр

• Universitaetsklinikum Münster — Münster

Португалия · 1 центр

• Unidade Local de Saúde de Santo António, E.P.E — Porto

Идентификаторы

NCT: NCT06657859 · GLM101-007

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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