A Study of SGT-212 Gene Therapy in Friedreich's Ataxia

Официальное название

A Phase 1b First-in-Human, Open-Label, Dose-Finding Trial to Evaluate the Safety and Tolerability of SGT-212 Delivered Via Dual Intradentate Nucleus (IDN) and Intravenous (IV) Administration to Participants With Friedreich's Ataxia (FA)

Обзор

This is a phase 1b, first in-human, open-label, dose-finding study investigating the safety and tolerability of SGT-212 in participants with Friedreich's ataxia (FA). It will be delivered via dual intradentate nucleus (IDN) and intravenous (IV) administration to participants with FA. All participants will receive SGT-212 and will be enrolled in the study for approximately 5 years.

Вмешательства

• Препарат SGT-212
  Adeno-associated virus serotype AAVhu68 containing a codon-optimized complementary DNA (cDNA)

Первичные конечные точки

• Incidence and Severity of Treatment Emergent Adverse Events (TEAEs) [Срок оценки: Month 12]

Вторичные конечные точки (9)

• Incidence and Severity of TEAEs [Срок оценки: Months 18 and 60]
• Incidence and Severity of Treatment-emergent Serious adverse events (SAEs) [Срок оценки: Months 18 and 60]
• Number of Treatment-emergent deaths [Срок оценки: Months 18 and 60]
• Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) [Срок оценки: Baseline, Months 18 and 60]
• Number of Participants with Change from Baseline in Significant Abnormalities in Laboratory Tests [Срок оценки: Baseline, Months 18 and 60]
• Number of Participants with Change from Baseline in Significant Abnormalities in Vital Signs [Срок оценки: Baseline, Months 18 and 60]
• Number of Participants with Change from Baseline in Significant Abnormalities in Physical Examination Findings [Срок оценки: Baseline, Months 18 and 60]
• Number of Participants with Change from Baseline in Innate and Adaptive Immune Responses [Срок оценки: Baseline, Months 18 and 60]
• Change from Baseline in Blood Biomarkers Including Inflammatory Markers [Срок оценки: Baseline, Month 12]

Критерии участия

Критерии включения

• Has history of FA symptom onset ≤25 years of age
• Has a clinical and genetic diagnosis of FA
• Has a staging score of ≥1 but <6 on the Friedreich's Ataxia Rating Scale (FARS) Functional Disability Staging Score
• Is willing to agree to the following rules for use of omaveloxolone (Skyclarys):

• For a candidate who is currently taking omaveloxolone, has been on a stable dose for 12 weeks, expects to continue taking omaveloxolone at that dose throughout the study, and is willing to stop taking omaveloxolone at the direction of the Investigator or Sponsor's Medical Monitor if evidence of transaminitis or synthetic liver dysfunction is detected during the study
• For a candidate who is not actively taking omaveloxolone, at least 12 weeks have passed since the last dose and the candidate agrees not to resume omaveloxolone during the 18-month period after SGT-212 infusion NOTE: The use of any other approved or investigational medicinal product for the treatment of FA should be discussed with the study team.

Критерии исключения

• Antibodies against adeno-associated virus serotype 9 (AAV9)
• Has a modified FARS (mFARS) score <20
• Has a body weight ≤25 kilogram (kg) or has body mass index (BMI) ≥33 kg/m\^2
• Has a contraindication to endomyocardial biopsy (EMB) or cardiac catheterization
• Is unable to undergo cardiac and brain MRI with contrast, including hypersensitivity to gadolinium contrast agent, presence of a non-MRI-compatible cardiac pacemaker, presence of a non-MRI-compatible implantable cardiac defibrillator, or physical condition (e.g., contractures)
• Has uncontrolled diabetes as defined by a hemoglobin (Hb) A1c >9%
• Has participated in recent interventional clinical studies or received any investigational therapy administered within 3 months or 5 half-lives (whichever is longer) prior to Screening
• Has received gene therapy at any time
• Has contraindications to receiving corticosteroids
• Has any contraindication to the surgical procedures involved with IDN infusion of SGT-212
• Has any known cardiac disease not related to FA including known obstructive coronary artery disease (CAD)
• Other Inclusion/Exclusion criteria to be applied as per protocol.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• The University of California, Los Angeles (UCLA) — Los Angeles
• The Ohio State University — Columbus
• The Children's Hospital of Philadelphia (CHOP) — Philadelphia

Идентификаторы

NCT: NCT07180355 · SGT-212-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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