Gene therapy for X-linked retinoschisis

A Phase 1/2/3, Open-Label, Dose Escalation, Dose Expansion and Randomized, Controlled Study to Evaluate the Safety and Efficacy of ATSN-201 Gene Therapy in Subjects With RS1-Associated X-linked Retinoschisis (LIGHTHOUSE)

This study is testing a one-time gene therapy injection for boys and men with X-linked retinoschisis to see if it's safe and how well they can tolerate it over five years.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 97 (estimated)
• Ages: 6 Years and up
• Sex: All
• Sponsor: Atsena Therapeutics Inc. (Industry-sponsored)
• Locations: 4 sites (Los Angeles, California and 3 other locations)
• Trial ID: NCT05878860 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and tolerability of ATSN-201, a gene therapy, in male patients aged 6 years and older diagnosed with RS1-associated X-linked retinoschisis. Participants will receive a one-time subretinal injection of ATSN-201 in one eye, and the effects will be monitored over a period of five years. The study aims to determine how well the treatment is tolerated and its safety profile in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates are male patients aged 6 years and older with a clinical diagnosis of X-linked retinoschisis due to RS1 mutations.

Not a fit: Patients with significant pre-existing eye conditions or recent ocular surgeries may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could improve vision and quality of life for patients with X-linked retinoschisis.

How similar studies have performed: While gene therapy for retinal conditions is an emerging field, this specific approach is novel and has not been extensively tested in prior studies.

Eligibility criteria

Part A and B:

Inclusion Criteria:

1. Age ≥ 18 for Cohorts 1 through 4, and age ≥ 6 years and \< 18 years for Cohort 5.
2. Male patients with clinical diagnosis of XLRS caused by mutations in RS1.
3. Best corrected visual acuity (BCVA) in study eye of 34 to 73 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (corresponding to a Snellen acuity of 20/200 to 20/40).
4. Presence of foveal schisis and /or parafoveal/perifoveal schisis in the study eye on SD-OCT per the Principal Investigator.

Exclusion Criteria:

1. Pre-existing eye conditions in the study eye that would contribute significantly to an increased risk of visual loss from a subretinal injection (eg, advanced glaucoma, optic neuropathy, uveitis, corneal transplants).
2. Any intraocular surgery (including laser treatment) in the study eye within 6 months prior to Screening or any intraocular surgery anticipated in the study eye during the first 12 months of the study.
3. Treatment in a prior ocular gene or cell therapy study.

Part C:

Inclusion Criteria:

Note: For patients ineligible for bilateral dosing based on the ocular exclusion criteria, the same eye must meet all ocular inclusion criteria, but none of the ocular exclusion criteria, to be eligible for unilateral dosing.

General All of the following criteria must be met for unilateral or bilateral dosing.

1. Age ≥ 6 years.
2. Genetically male patients with clinical diagnosis of XLRS caused by pathogenic or likely pathogenic mutations in RS1 OR Genetically female patients with clinical diagnosis of XLRS caused by biallelic pathogenic or likely pathogenic mutations in RS1.

   Ocular At least 1 eye must meet all of the following criteria for both unilateral and bilateral dosing.
3. BCVA of 34 to 73 ETDRS letters (corresponding to a Snellen acuity of 20/200 to 20/40).
4. Presence of foveal schisis on SD-OCT.

Exclusion Criteria:

General None of the following criteria can be met for unilateral or bilateral dosing.

1. Treatment with any carbonic anhydrase inhibitor (oral or topical) within 1 month prior to Screening.
2. Treatment in a prior ocular gene or cell therapy study.
3. Absence of macular schisis.
4. BCVA better than 75 ETDRS letters (corresponding to a Snellen acuity of 20/32).
5. Pre-existing eye conditions that would contribute significantly to an increased risk of visual loss from a subretinal injection (eg, advanced glaucoma, optic neuropathy, uveitis, corneal transplants).
6. Any intraocular surgery (including laser treatment) within 6 months prior to Screening or any intraocular surgery anticipated during the first 12 months of the study.

Where this trial is running

Los Angeles, California and 3 other locations

• Children's Hospital of Los Angeles — Los Angeles, California, United States (Recruiting)
• Bascom Palmer Eye Institute — Miami, Florida, United States (Recruiting)
• Oregon Health Sciences University — Portland, Oregon, United States (Recruiting)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Study coordinator: Atsena Therapeutics Clinical Trials

Conditions X-linked Retinoschisis; XLRS, RS1