Friedreich's Ataxia (FA)
Conditions
Keywords
SGT-212, Gene Therapy, Frataxin, Repeat Expansion, Neuromuscular, Cardiac, Ataxia, Movement Disorder, Rare disease, AAV, AAVhu68
Brief summary
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.
Interventions
DRUGSGT-212
Adeno-associated virus serotype AAVhu68 containing a codon-optimized complementary DNA (cDNA)
Sponsors
Solid Biosciences Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* 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): 1. 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 2. 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.
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and Severity of Treatment Emergent Adverse Events (TEAEs) | Month 12 |
Secondary
| Measure | Time frame |
|---|---|
| Incidence and Severity of TEAEs | Months 18 and 60 |
| Incidence and Severity of Treatment-emergent Serious adverse events (SAEs) | Months 18 and 60 |
| Number of Treatment-emergent deaths | Months 18 and 60 |
| Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline, Months 18 and 60 |
| Number of Participants with Change from Baseline in Significant Abnormalities in Laboratory Tests | Baseline, Months 18 and 60 |
| Number of Participants with Change from Baseline in Significant Abnormalities in Vital Signs | Baseline, Months 18 and 60 |
| Number of Participants with Change from Baseline in Significant Abnormalities in Physical Examination Findings | Baseline, Months 18 and 60 |
| Number of Participants with Change from Baseline in Innate and Adaptive Immune Responses | Baseline, Months 18 and 60 |
| Change from Baseline in Blood Biomarkers Including Inflammatory Markers | Baseline, Month 12 |
Countries
United States
Contacts
CONTACTSolid Biosciences Clinical Trials
Outcome results
None listed