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

About

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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

40 Years

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):
- 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.

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)