Safety and Efficacy Trial of HG004 for Leber Congenital Amaurosis Related to Rpe65 Gene Mutations (STAR)

A Phase 1/2, Open-label, Multi-national, Multiple-cohort, Dose-escalation Study to Evaluate the Safety, Tolerability, and Efficacy of HG004 Gene Therapy in Subjects with RPE65-associated Leber Congenital Amaurosis Type 2 (LCA2)

The purpose of the study is to determine whether HG004 as gene therapy is safe and effective for the treatment of Leber Congenital Amaurosis caused by mutations in RPE65 gene.

Inclusion Criteria:

• Male or females between 6 and 50 years of age at the time of signing the informed consent form.
• Willing to adhere to protocol as evidenced by written informed consent or parental permission and subject assent.
• Clinical confirmed diagnosis of Leber congenital amaurosis (LCA) and molecular diagnosis of LCA due to RPE65 mutations.
• Ability to perform tests of visual and retinal function.
• Visual acuity of ≤ 20/80 or visual field less than 20 degrees in the eye to be injected.
• Acceptable hematology, clinical chemistry, and urine laboratory parameters.

Exclusion Criteria:

• Pre-existing eye conditions that would preclude the planned surgery or interfere with interpretation of study endpoints or complications of surgery (e.g., glaucoma requiring upcoming surgery, corneal or significant lenticular opacities).
• Presence of epiretinal membrane by OCT.
• Complicating systemic diseases or clinically significant abnormal baseline laboratory values.
• Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter ocular function.
• Prior ocular surgery within six months.
• Prior gene therapy or oligonucleotide therapy treatments.
• Any condition which leads the investigator to believe that the participant cannot comply with the protocol requirements or that may place the participant at an unacceptable risk for participation.