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This study will evaluate the safety and efficacy of ATSN-201 in subjects ≥ 6 years of age with RS1-associated X-linked retinoschisis (XLRS).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1, Low Dose | Experimental |
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| Cohort 2, High Dose | Experimental |
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| Cohort 3, Mid Dose | Experimental |
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| Cohort 4, Low Volume | Experimental |
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| Cohort 4, High Volume | Experimental |
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| Cohort 4, Control | No Intervention | ||
| Cohort 5, Pediatric | Experimental |
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| Cohort 6, Treatment | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ATSN-201 | Biological | AAV.SPR-hGRK1-hRS1syn |
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| 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 |
| 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 |
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Part A and B:
Inclusion Criteria:
Exclusion Criteria:
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.
Age ≥ 6 years.
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.
BCVA of 34 to 73 ETDRS letters (corresponding to a Snellen acuity of 20/200 to 20/40).
Presence of foveal schisis on SD-OCT.
Exclusion Criteria:
General None of the following criteria can be met for unilateral or bilateral dosing.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Atsena Therapeutics Clinical Trials | Contact | 984-261-2001 | clinicaltrials@atsenatx.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Los Angeles | Recruiting | Los Angeles | California | 90027 | United States |
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| ID | Term |
|---|---|
| D041441 | Retinoschisis |
| ID | Term |
|---|---|
| D012162 | Retinal Degeneration |
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
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Cohort 4 will be partially masked. Cohort 6 will be partially masked.
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| Cohort 6, Control | No Intervention |
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 |
| Bascom Palmer Eye Institute | Recruiting | Miami | Florida | 33136 | United States |
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| Oregon Health Sciences University | Recruiting | Portland | Oregon | 97239 | United States |
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| Children's Hospital of Philadelphia | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
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