Single Ascending Dose Study in Participants With LCA10

Open-Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Efficacy of EDIT-101 in Adult and Pediatric Participants With Leber Congenital Amaurosis Type 10 (LCA10), With Centrosomal Protein 290 (CEP290)-Related Retinal Degeneration Caused by a Compound Heterozygous or Homozygous Mutation Involving c.2991+1655A>G in Intron 26 (IVS26) of the CEP290 Gene ("LCA10-IVS26")

The purpose of this study is to evaluate the safety, tolerability and efficacy of a single escalating doses of EDIT-101 administered via subretinal injection in participants with LCA10 caused by a homozygous or compound heterozygous mutation involving c.2991+1655A>G in intron 26 of the CEP290 gene ("LCA10-IVS26").

This is an open-label, single ascending dose study of EDIT-101 in adult and pediatric (ie, ages 3 to 17) participants with LCA10-IVS26. Up to 34 participants will be enrolled in up to 5 cohorts to evaluate up to 3 dose levels of EDIT-101 in this study. EDIT-101 is a novel gene editing product designed to eliminate the mutation on the CEP290 gene that results in the retinal degeneration that defines LCA10-IVS26.

Inclusion Criteria:

• Male or female

• At least 3 years of age at screening with CEP290-related retinal degeneration caused by a homozygous or compound heterozygous mutation involving c.2991+1655A>G in IVS26 of the CEP290 gene.

• Visual Acuity:

  • Sentinel participant will have severe vision loss with a logMAR BCVA of ≥1.6 to 3.9 (20/800 or worse to LP) in the study eye
  • Non-sentinel participants must have BCVA between 1.0 - 3.0 logMAR in the study eye

Exclusion Criteria:

• Other known disease-causing mutations
• Achieves a passing score for the mobility course at the most difficult level
• In either eye, active systemic or ocular/intraocular infection or inflammation
• In either eye, history of steroid-responsive intraocular pressure with increases > 25 mm Hg following corticosteroid exposure
• Any vaccination/immunization in the last 28 days before screening
• Inability or unwillingness to take oral prednisone
• Prior gene therapy or oligonucleotide treatment