ATSN-201 Gene Therapy in RS1-Associated X-linked Retinoschisis (LIGHTHOUSE)

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 will evaluate the safety and efficacy of ATSN-201 in subjects ≥ 6 years of age with RS1-associated X-linked retinoschisis (XLRS).

Study Overview

• Status: Recruiting
• Conditions: X-linked Retinoschisis
• Intervention / Treatment: Biological: ATSN-201

Detailed Description

The study is designed in three parts: a dose escalation phase (Part A), a dose expansion phase (Part B) and a randomized, controlled phase (Part C).

In Part C of the study, eligible patients who enroll in this study will be randomly assigned to be treated with ATSN-201 or to have no treatment; subjects assigned to ATSN-201 will receive the drug as a one-time subretinal injection of ATSN-201 in one eye or both eyes, depending on whether only one or both eyes meet criteria for treatment. Subjects will have regular assessments for 1 year as part of the Main Study Period and additional assessments over the next 4 years as part of the Extension Study Period.

Subjects who do not receive treatment as part of the control group can choose to receive ATSN-201 in one or both eyes after the 1-year Main Study Period if eligible.

• Study Type: Interventional
• Enrollment (Estimated): 97
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Atsena Therapeutics Clinical Trials; Phone Number: 984-261-2001; Email: clinicaltrials@atsenatx.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital of Los Angeles
      • Principal Investigator: Aaron Nagiel, MD, PhD
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • Bascom Palmer Eye Institute
      • Principal Investigator: Byron Lam, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health Sciences University
      • Principal Investigator: Lesley Everett, MD, PhD, MPhil
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Principal Investigator: Tomas Aleman, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Cohort 4, Control
Experimental: Cohort 1, Low Dose	Biological: ATSN-201; AAV.SPR-hGRK1-hRS1syn
Experimental: Cohort 2, High Dose	Biological: ATSN-201; AAV.SPR-hGRK1-hRS1syn
Experimental: Cohort 3, Mid Dose	Biological: ATSN-201; AAV.SPR-hGRK1-hRS1syn
Experimental: Cohort 4, Low Volume	Biological: ATSN-201; AAV.SPR-hGRK1-hRS1syn
Experimental: Cohort 4, High Volume	Biological: ATSN-201; AAV.SPR-hGRK1-hRS1syn
Experimental: Cohort 5, Pediatric	Biological: ATSN-201; AAV.SPR-hGRK1-hRS1syn
Experimental: Cohort 6, Treatment	Biological: ATSN-201; AAV.SPR-hGRK1-hRS1syn
No Intervention: Cohort 6, Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A (Dose Escalation) and Part B (Dose Expansion): 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
Part C (Phase 3, Randomized, Controlled) Effect of ATSN-201 on visual function.	Proportion of subjects ≥12 years of age with improvement ≥ 7dB from baseline in microperimetry across prespecified loci in the study eye.	From baseline to week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A and Part B: Visual acuity as assessed by best-corrected visual acuity	Change in best-corrected visual acuity (BCVA).	From baseline to week 52
Part A and Part B: Visual acuity as assessed by low-luminance visual acuity	Change in low-luminance visual acuity (LLVA).	From baseline to week 52
Part A and Part B: Visual function as assessed by contrast sensitivity	Change in contrast sensitivity.	From baseline to week 52
Part A and Part B: Visual function as assessed by microperimetry	Change in microperimetry.	From baseline to week 52
Part A and Part B: Macular structure as assessed by spectral domain optical coherence tomography	Change in spectral domain optical coherence tomography (SD-OCT).	From baseline to week 52
Part A and Part B: Macular structure as assessed by fundus autofluorescence	Change in fundus autofluorescence (FAF).	From baseline to week 52
Part A and Part B: 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
Part A and Part B: 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
Part A and Part B: Subject-reported visual function as assessed by the MRDQ in subjects 13 years of age or greater.	Description: Change in the Michigan Retinal Degeneration Questionnaire (MRDQ) score for subjects 13 years of age or greater.	From baseline to week 52
Part C: Macular structure as assessed by spectral domain optical coherence tomography	Change in spectral domain optical coherence tomography (SD-OCT).	From baseline to week 52
Part C: Visual acuity as assessed by best-corrected visual acuity or low-luminance visual acuity	Change in best-corrected visual acuity (BCVA) or low luminance visual acuity (LLVA).	From baseline to week 52
Part C: Visual acuity as assessed by best-corrected visual acuity as measured by Early Treatment Diabetic Retinopathy Study chart	Change in best-corrected visual acuity (BCVA) as assessed by ETDRS.	From baseline to week 52
Part C: Visual acuity as assessed by low luminance visual acuity as measured by Early Treatment Diabetic Retinopathy Study chart	Description: Change in low luminance visual acuity (LLVA) as assessed by ETDRS.	From baseline to week 52
Part C: Visual function as assessed by microperimetry	Change in microperimetry for subjects age 12 or greater.	From baseline to week 52
Part C: Functional vision as assessed by reading speed	Change from baseline in reading speed as measured by MNREAD for subjects 8 years of age and older.	From baseline to week 52
Part C: Subject-reported visual function as assessed by the MRDQ in subjects 13 years of age or greater	Change in the Michigan Retinal Degeneration Questionnaire (MRDQ) score for subjects 13 years of age or greater.	From baseline to week 52
Part C: 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 ages 6-13 years of age.	From baseline to week 52
Part C: Subject perception of change and severity (PGIC/PGIS)	Patient global impression of change and severity (PGIC/PGIS).	From baseline to week 52
Part C: Evaluate the safety of ATSN-201	Incidence of treatment emergent adverse events (TEAEs).	From baseline to week 52

Collaborators and Investigators

• Sponsor: Atsena Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2023
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2033

Study Registration Dates

• First Submitted: May 12, 2023
• First Submitted That Met QC Criteria: May 24, 2023
• First Posted (Actual): May 26, 2023

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: XLRS, RS1
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Retinoschisis
• Other Study ID Numbers: ATSN-201-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No