X-linked Retinoschisis
Conditions
Keywords
XLRS, RS1
Brief summary
This study will evaluate the safety and efficacy of ATSN-201 in subjects ≥ 6 years of age with RS1-associated X-linked retinoschisis (XLRS).
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. Some subjects may have all their study visits at a surgery site. Some subjects may go to one study site (a medical site) to determine eligibility and another study site (a surgery site) to have surgery - including pre-operative care and approximately 1-week of post-operative care per treated eye. After the surgery, they will go back to the other study site (the medical site) to complete the follow-up visits. 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.
Interventions
BIOLOGICALATSN-201
AAV.SPR-hGRK1-hRS1syn
Sponsors
Atsena Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Cohort 4 will be partially masked. Cohort 6 will be partially masked.
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A (Dose Escalation) and Part B (Dose Expansion): Safety and tolerability as assessed by dose-limiting toxicities and treatment-emergent adverse events | From baseline to week 52 | Incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs). |
| Part C (Phase 3, Randomized, Controlled) Effect of ATSN-201 on visual function. | From baseline to week 52 | Proportion of subjects ≥12 years of age with improvement ≥ 7dB from baseline in microperimetry across prespecified loci in the study eye. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part C: Evaluate the safety of ATSN-201 | From baseline to week 52 | Incidence of treatment emergent adverse events (TEAEs). |
| Part A and Part B: Visual acuity as assessed by best-corrected visual acuity | From baseline to week 52 | Change in best-corrected visual acuity (BCVA). |
| Part A and Part B: Visual acuity as assessed by low-luminance visual acuity | From baseline to week 52 | Change in low-luminance visual acuity (LLVA). |
| Part A and Part B: Visual function as assessed by contrast sensitivity | From baseline to week 52 | Change in contrast sensitivity. |
| Part A and Part B: Visual function as assessed by microperimetry | From baseline to week 52 | Change in microperimetry. |
| Part A and Part B: Macular structure as assessed by spectral domain optical coherence tomography | From baseline to week 52 | Change in spectral domain optical coherence tomography (SD-OCT). |
| Part A and Part B: Macular structure as assessed by fundus autofluorescence | From baseline to week 52 | Change in fundus autofluorescence (FAF). |
| Part A and Part B: Subject-reported visual function as assessed by the NEI VFQ-25 in adult subjects | From baseline to week 52 | 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. |
| Part A and Part B: Subject-reported visual function as assessed by the CVAQC in pediatric subjects | From baseline to week 52 | 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. |
| Part A and Part B: Subject-reported visual function as assessed by the MRDQ in subjects 13 years of age or greater. | From baseline to week 52 | Description: Change in the Michigan Retinal Degeneration Questionnaire (MRDQ) score for subjects 13 years of age or greater. |
| Part C: Macular structure as assessed by spectral domain optical coherence tomography | From baseline to week 52 | Change in spectral domain optical coherence tomography (SD-OCT). |
| Part C: Visual acuity as assessed by best-corrected visual acuity or low-luminance visual acuity | From baseline to week 52 | Change in best-corrected visual acuity (BCVA) or low luminance visual acuity (LLVA). |
| Part C: Visual acuity as assessed by best-corrected visual acuity as measured by Early Treatment Diabetic Retinopathy Study chart | From baseline to week 52 | Change in best-corrected visual acuity (BCVA) as assessed by ETDRS. |
| Part C: Visual acuity as assessed by low luminance visual acuity as measured by Early Treatment Diabetic Retinopathy Study chart | From baseline to week 52 | Description: Change in low luminance visual acuity (LLVA) as assessed by ETDRS. |
| Part C: Visual function as assessed by microperimetry | From baseline to week 52 | Change in microperimetry for subjects age 12 or greater. |
| Part C: Functional vision as assessed by reading speed | From baseline to week 52 | Change from baseline in reading speed as measured by MNREAD for subjects 8 years of age and older. |
| Part C: Subject-reported visual function as assessed by the CVAQC in pediatric subjects | From baseline to week 52 | Change in the Cardiff Visual Ability Questionnaire for Children (CVAQC) score for pediatric subjects ages 6-13 years of age. |
| Part C: Subject-reported visual function as assessed by the MRDQ in subjects 13 years of age or greater | From baseline to week 52 | Change in the Michigan Retinal Degeneration Questionnaire (MRDQ) score for subjects 13 years of age or greater. |
| Part C: Subject perception of change and severity (PGIC/PGIS) | From baseline to week 52 | Patient global impression of change and severity (PGIC/PGIS). |
Countries
Canada, United Kingdom, United States
Contacts
CONTACTAtsena Therapeutics Clinical Trials
Outcome results
None listed