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

Phase 3RecruitingNCT05878860

Atsena Therapeutics Inc.97 enrolled

Overview

This study will evaluate the safety and efficacy of ATSN-201 in subjects ≥ 5 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. 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. If the subject is not eligible at the Month 12 visit, eligibility may be reassessed at the Month 18 visit.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

X-linked Retinoschisis

Interventions

ATSN-201BIOLOGICAL

AAV.SPR-hGRK1-hRS1syn

Eligibility

Sex: ALLMin age: 5 Years

Medical Language ↔ Plain English

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 ≥ 5 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 (laser treatment is allowed as long as it occurs at least 2 weeks before surgery).

Locations (21)

Associated Retina Consultants

Phoenix, Arizona, United States

Outcomes

Primary Outcomes

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).

Time frame: From baseline to week 52

Part C (Phase 3, Randomized, Controlled) Effect of ATSN-201 on visual function.

Proportion of subjects with improvement ≥ 7dB from baseline in microperimetry across prespecified loci in the study eye.

Time frame: From baseline to week 52

Secondary Outcomes

Part A and Part B: Visual acuity as assessed by best-corrected visual acuity

Change in best-corrected visual acuity (BCVA).

Time frame: 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).

Time frame: From baseline to week 52

Part A and Part B: Visual function as assessed by contrast sensitivity

Change in contrast sensitivity.

Time frame: From baseline to week 52

Part A and Part B: Visual function as assessed by microperimetry

Change in microperimetry.

Time frame: 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).

Time frame: From baseline to week 52

Central Contacts

Atsena Therapeutics Clinical Trials

CONTACT

984-261-2001 clinicaltrials@atsenatx.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Shiley Eye Institute

La Jolla, California, United States

NOT_YET_RECRUITING

Children's Hospital of Los Angeles

Los Angeles, California, United States

RECRUITING

Stanford University

Palo Alto, California, United States

NOT_YET_RECRUITING

UC San Francisco

San Francisco, California, United States

RECRUITING

Bascom Palmer Eye Institute

Miami, Florida, United States

RECRUITING

Massachusetts Eye and Ear

Boston, Massachusetts, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, United States

NOT_YET_RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

RECRUITING

...and 11 more locations

Part A and Part B: Macular structure as assessed by fundus autofluorescence

Change in fundus autofluorescence (FAF).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: From baseline to week 52

Part C: Visual function as assessed by microperimetry

Change in microperimetry for subjects.

Time frame: 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.

Time frame: 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.

Time frame: 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 5-13 years of age.

Time frame: From baseline to week 52

Part C: Subject perception of change and severity (PGIC/PGIS)

Patient global impression of change and severity (PGIC/PGIS).

Time frame: From baseline to week 52

Part C: Evaluate the safety of ATSN-201

Incidence of treatment emergent adverse events (TEAEs).

Time frame: From baseline to week 52

Part C: To evaluate the quality of life in subjects treated with ATSN-201

Change from Baseline in EQ-5D-5L Health Index score and VAS score at Month 12 for subjects ≥ 12 years of age in the ATSN-201 group vs. controls.

Time frame: From baseline to week 52

Part C: Change from Baseline in EQ-5D-Y-5L Health

Index score and VAS score at Month 12 for subjects ≥ 8 to \< 12 years of age in the ATSN201 group vs. controls.

Time frame: From baseline to week 52