Study of Safety, Tolerability and Efficacy of GB221 in Infants With Spinal Muscular Atrophy Type 1

Официальное название

A Phase 1-2, Open-Label, Multicenter Study to Assess the Safety, Tolerability and Efficacy of a Single Dose of GB221 Delivered Into the Cisterna Magna of Pediatric Participants From 2 Weeks to Younger Than 12 Months of Age With Spinal Muscular Atrophy Type 1

Обзор

GB221 is a gene therapy that delivers a working SMN1 gene to the motor neurons of people with spinal muscular atrophy (SMA) Type 1. This study will evaluate the safety, tolerability and efficacy of GB221 in two groups: 1. participants aged from 2 weeks to younger than 12 months presenting with symptoms of SMA Type 1 who have never received a treatment OR are receiving the drug risdiplam 2. participants aged from 2 weeks to younger than 5 months who are at risk of developing SMA Type 1 (presymptomatic) and have never received treatment OR are receiving the drug risdiplam.

Вмешательства

• Биопрепарат GB221
  GB221

Первичные конечные точки

• Number of participants with treatment-related adverse events (AEs) and serious adverse events (SAEs) at Grade 3 or higher as characterized by CTCAEv5.0 [Срок оценки: Up to 18 months across multiple visits]
• Number of Participants with Clinically Significant Changes in Physical Functions [Срок оценки: Up to 18 months across multiple visits]
• Number of Participants with Clinically Significant Changes in Neurological Functions [Срок оценки: Up to 18 months across multiple visits]
• Number of Participants with Clinically Significant Changes in Vital signs [Срок оценки: Up to 18 months across multiple visits]
• Change in electrocardiogram results [Срок оценки: Up to 18 months across multiple visits]
• Change in serum cardiac troponin I levels [Срок оценки: Up to 18 months across multiple visits]
• Number of Participants with Clinically Significant Laboratory Abnormalities as Measured Using Hematology, Chemistry and Coagulation Tests [Срок оценки: Up to 18 months across multiple visits]
• Number of Participants with Clinically Significant Laboratory Abnormalities as Measured Using Urine and CSF Tests [Срок оценки: Up to 18 months across multiple visits]
• Change in markers of immunogenicity [Срок оценки: Up to 18 months across multiple visits]

Вторичные конечные точки (3)

• Assess the number of participants who experience permanent ventilation or death [Срок оценки: Up to 18 months across multiple visits]
• Percentage of infants with improvement in the motor milestones categories in Section 2 of the Hammersmith Infant Neurological Examination (HINE), with the exclusion of voluntary grasp. [Срок оценки: Baseline, 6 months and 18 months post dose.]
• Change from baseline in mean Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Score. [Срок оценки: Baseline, 6 months and 18 months post dose.]

Критерии участия

Критерии включения

• Symptomatic Participants

• Diagnosis of SMA Type 1 based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and up to 3 copies of SMN2
• Participants must be 2 weeks to < 12 months of age at the time of dosing with disease onset of during the first 6 months of life.
• Presymptomatic Participants

• At risk of SMA Type 1 based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and up to 2 copies of SMN2
• Participants must be 2 weeks to < 5 months (< 150 days) of age at the time of dosing.

Критерии исключения

• Any suspected or confirmed active viral infection at screening baseline (including HIV, Hepatitis B or C, or human T Cell lymphotropic viruses \[HTLV\])
• History of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry <95% saturation.
• Ongoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)
• Participation in a recent SMA treatment clinical trial that, in the opinion of the Investigator, creates unnecessary risks for gene transfer.
• Prior history of gene therapy for any indication, hematopoietic transplant or solid organ transplant
• Subjects with severe scoliosis
• Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Бразилия · 1 центр

• Hospital de Clínicas de Porto Alegre — Porto Alegre

Идентификаторы

NCT: NCT07070999 · GB221-101 · CHARISMA

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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