ATSN-201 Gene Therapy in RS1-Associated X-linked Retinoschisis

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of ATSN-201 in male subjects 6 to 64 years old with RS1-associated X-linked retinoschisis (XLRS).

Detailed Description
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Eligible patients who enroll in this study will receive a one-time subretinal injection of ATSN-201 in one eye. Safety and tolerability will be evaluated for 5 years.

Official Title
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A Phase 1/2, Open-Label, Dose Escalation and Dose Expansion Study to Evaluate the Safety and Tolerability of ATSN-201 Gene Therapy in Male Subjects With RS1-Associated X-linked Retinoschisis

Conditions
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X-linked Retinoschisis

Intervention / Treatment
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* Biological: ATSN-201


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 and < 65 years for Cohorts 1 through 3, and age ≥ 6 years and < 18 years for Cohort 4. Male patients with clinical diagnosis of XLRS caused by mutations in RS1. Best corrected visual acuity (BCVA) in both eyes of 34 to 73 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (corresponding to a Snellen acuity of 20/200 to 20/40). Exclusion Criteria: Pre-existing eye conditions in the study eye that would contribute significantly to an increased risk of visual loss from a subretinal injection. Any intraocular surgery (including laser treatment) in the study eye within 6 months prior or any intraocular surgery anticipated in the study eye during the first 12 months of the study. Treatment in a prior ocular gene or cell therapy study.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>ATSN-201 at Low Dose | Biological: ATSN-201<br>* AAV.SPR-hGRK1-hRS1syn<br>|
| Experimental: Cohort 2<br>ATSN-201 at High Dose | Biological: ATSN-201<br>* AAV.SPR-hGRK1-hRS1syn<br>|
| Experimental: Cohort 3, High Dose<br>ATSN-201 at High Volume | Biological: ATSN-201<br>* AAV.SPR-hGRK1-hRS1syn<br>|
| Experimental: Cohort 3, Low Dose<br>ATSN-201 at Low Volume | Biological: ATSN-201<br>* AAV.SPR-hGRK1-hRS1syn<br>|
| No Intervention: Cohort 3, Control<br> | |
| Experimental: Cohort 4, Pediatric<br>ATSN-201 at High Dose | Biological: ATSN-201<br>* AAV.SPR-hGRK1-hRS1syn<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as assessed by dose-limiting toxicities and treatment-emergent adverse events | Incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs). | From baseline to week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual acuity as assessed by best-corrected visual acuity | Change in best-corrected visual acuity (BCVA). | From baseline to week 52 | 
| Visual acuity as assessed by low-luminance visual acuity | Change in low-luminance visual acuity (LLVA). | From baseline to week 52 | 
| Visual function as assessed by contrast sensitivity | Change in contrast sensitivity. | From baseline to week 52 | 
| Visual function as assessed by full-field electroretinogram parameters | Change in full-field electroretinogram (ffERG) parameters. | From baseline to week 52 | 
| Visual function as assessed by microperimetry | Change in microperimetry. | From baseline to week 52 | 
| Visual function as assessed by static perimetry | Change in static perimetry. | From baseline to week 52 | 
| Macular structure as assessed by spectral domain optical coherence tomography | Change in spectral domain optical coherence tomography (SD-OCT). | From baseline to week 52 | 
| Macular structure as assessed by fundus autofluorescence | Change in fundus autofluorescence (FAF). | From baseline to week 52 | 
| Subject-reported visual function as assessed by the NEI VFQ-25 in adult subjects | Change in the National Eye Institute's Visual Function Questionnaire 25 (NEI VFQ-25) score for adult subjects with scores from 0 to 100 where a higher score indicates a better outcome. | From baseline to week 52 | 
| Subject-reported visual function as assessed by the CVAQC in pediatric subjects | Change in the Cardiff Visual Ability Questionnaire for Children (CVAQC) score for pediatric subjects with scores from -3.00 to +2.80 where a higher score indicates a worse outcome. | From baseline to week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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XLRS, RS1