Study of Subretinally Injected ATSN-101 Administered in Patients With Leber Congenital Amaurosis Caused by Biallelic Mutations in GUCY2D

A Phase 1/2 Dose Escalation Study of Subretinally Injected ATSN-101 Administered in Patients With Leber Congenital Amaurosis Caused by Biallelic Mutations in GUCY2D

Primary Objective:

To evaluate the safety and tolerability of ascending doses of ATSN-101 administered as a unilateral subretinal injection in patients with Leber Congenital Amaurosis (LCA) caused by autosomal recessive guanylate cyclase 2D (GUCY2D) mutations (GUCY2D-LCA).

Secondary Objective:

To evaluate the efficacy of ascending doses of ATSN-101 administered as a unilateral subretinal injection in patients with GUCY2D-LCA.

Study Overview

• Status: Active, not recruiting
• Conditions: Leber Congenital Amaurosis; LCA; LCA1
• Intervention / Treatment: Drug: Prednisone; Drug: Triamcinalone Acetonide; Drug: 1% Prednisolone; Drug: Trimethoprim/polymyxin B; Drug: ATSN-101; Drug: ATSN-101 Diluent Solution

Detailed Description

Study duration per participant is approximately 112 weeks including: an approximately 56-day screening/baseline period, an approximately 52-week study observation period including 1 treatment day, and an approximately 52-week safety follow-up period. The end of study visit will be approximately 260 weeks after the Investigational Medicinal Product (IMP) administration.

The study is separated into 2 parts including a dose escalation phase (Part A) and a dose expansion phase (Part B). In Part B participants will be treated at the maximum tolerated dose (MTD) or maximum administered dose (MAD) determined from Part A.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute - Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Scheie Eye Institute, University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria :

• Male or female participant with clinical diagnosis of Leber congenital amaurosis caused by biallelic mutations in the GUCY2D (retinal guanylate cyclase) gene with all of the following: a) Documented mutations in both alleles of the GUCY2D gene per testing in a CLIA-approved laboratory, b) For Cohort 1-3, best corrected visual acuity (BCVA) of 20/200 or worse in the eye to be injected; subsequent cohorts may include BCVA of 20/80 or worse in the eye to be injected, c) Photoreceptor (outer nuclear) layer structure identifiable on an optical coherence tomography (OCT) scan across the central retina.
• Age ≥18 years for Cohorts 1 through 4, and age ≥ 6 years and <18 years for Cohort 5.
• Male and female participants must follow the contraception requirements of the trial.
• Participants must agree to not donate blood, organs, tissues, cells or sperm for at least three months following ATSN-101 administration.

Exclusion criteria:

• Complicating systemic diseases (such as medical conditions causing immunosuppression) that would preclude the gene transfer, ocular surgery or planned study procedures.
• History of human immunodeficiency virus (HIV) infection.
• Pre-existing eye conditions in the study eye that would preclude the planned surgery or interfere with the assessment and interpretation of study endpoints: for example, glaucoma or optic neuropathy that has resulted in significant visual loss, corneal or lenticular abnormalities or opacities that would preclude view of the fundus or performance of the outcome measures, uveitis, retinopathy and maculopathy that in the opinion of the Investigator are causing significant visual loss.
• Presence of significant ocular abnormalities in the study eye that in the opinion of the Investigator would preclude the planned surgery, effective safety follow-up, or interfere with the interpretation of study endpoints (eg, glaucoma, corneal or significant lens abnormalities or opacities, pre-existing uveitis, intraocular infection, choroidal neovascularization).
• Any contraindication to the planned surgical procedure, such as contraindications to the use of anaesthesia or allergy to medications planned in the peri-operative period.
• Known allergy or hypersensitivity to any component of the investigational medicinal product (IMP), diagnostic agents used during the study or medications planned for use in the peri-operative period, particularly corticosteroids.
• Women who are pregnant (defined as positive beta-Human Chorionic Gonadotropin (HCG) blood or urine test), lactating or breastfeeding.
• Any ocular procedure, either planned or performed within 6 months of Day 1, which would interfere with the planned surgery or the interpretation of study endpoints in the opinion of the Principal Investigator (PI).
• Laboratory test abnormalities or abnormalities in electrocardiogram that in the opinion of the PI would make the participant unsuitable for participation in the study.
• Significant intercurrent illness or infection during the 28 days prior to enrollment.
• Current substance use disorder.
• Use of any investigational agent administered within 5 times the elimination half-life of that investigational agent prior to ATSN-101 administration.
• Enrollment in any other clinical treatment study, for any condition, including those relating to GUCY2D-LCA, throughout the duration of the ATSN-101 study participation.
• Use of anticoagulation therapy within two weeks prior to surgery.
• Use of immunosuppressive medications.
• Current, planned during the course of this trial, or past (within 5 times the elimination half-life of that therapy prior to ATSN-101 administration) use of anti-viral therapy that would inactivate the investigational agent.
• Received gene therapy within the last 15 years.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ATSN-101; ATSN-101 single dose according to an ascending dose design (dose escalation phase) or ATSN-101 single dose (dose expansion phase)

Drug: Prednisone; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Triamcinalone Acetonide; Pharmaceutical form:Suspension Route of administration: Peri-ocular injection; Drug: 1% Prednisolone; Pharmaceutical form:Suspension Route of administration: Drops; Drug: Trimethoprim/polymyxin B; Pharmaceutical form:Solution Route of administration: Topical; Drug: ATSN-101; Pharmaceutical form:Solution for intraocular administration Route of administration: Subretinal injection; Drug: ATSN-101 Diluent Solution; Pharmaceutical form:Solution for parenteral use Route of administration: Subretinal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) From Baseline up to the End of the Observation Period	Number of participants with treatment-emergent AEs will be summarized in each cohort (this includes cohorts 1 - 5)	From Baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline of Best-Corrected Visual Acuity (BCVA) Between the Treated and Untreated Eyes	Mean change from Baseline to Week 52 in BCVA (LogMAR) in the treated eye and untreated eye (control). In logMAR notation (logarithm of the minimum angle of resolution) is interpreted as follows: Lower LogMAR values indicates better vision. Higher LogMAR values indicates worse vision.	Baseline to Week 52
Change From Baseline of Sensitivity Between the Treated and Untreated Eye - Light Adapted	Mean change from Baseline to Week 52 in sensitivity as measured by the full-field stimulus testing - Light Adapted in the treated eye and untreated eye. Full-field stimulus testing was performed for three stimulus colors - blue, red, and white.	Baseline to Week 52
Mean Change From Baseline of Sensitivity Between the Treated and Untreated Eye - Dark Adapted	Mean change from Baseline to Week 52 in sensitivity as measured by the full-field stimulus testing - Dark Adapted in the treated eye and untreated eye. Full-field stimulus testing was performed for three stimulus colors - blue, red, and white.	Baseline to Week 52
Number of Participants With Adverse Events (AEs) From Baseline up to the End of the Observation Period	Number of participants with treatment-emergent AEs will be summarized in each cohort (this includes cohorts 1 - 5)	From Baseline to Week 260
Change From Baseline of Best-Corrected Visual Acuity (BCVA) Between the Treated and Untreated Eyes	Mean change from Baseline to Week 260 in BCVA (LogMAR) in the treated eye and untreated eye (control). In logMAR notation (logarithm of the minimum angle of resolution) is interpreted as follows: Lower LogMAR values indicates better vision. Higher LogMAR values indicates worse vision.	Baseline to Week 260
Change From Baseline of Sensitivity Between the Treated and Untreated Eye - Light Adapted	Mean change from Baseline to Week 260 in sensitivity as measured by the full-field stimulus testing - Light Adapted in the treated eye and untreated eye. Full-field stimulus testing was performed for three stimulus colors - blue, red, and white.	Baseline to Week 260
Mean Change From Baseline of Sensitivity Between the Treated and Untreated Eye - Dark Adapted	Mean change from Baseline to Week 260 in sensitivity as measured by the full-field stimulus testing - Dark Adapted in the treated eye and untreated eye. Full-field stimulus testing was performed for three stimulus colors - blue, red, and white.	Baseline to Week 260

Collaborators and Investigators

• Sponsor: Atsena Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2019
• Primary Completion (Actual): May 19, 2023
• Study Completion (Estimated): May 19, 2027

Study Registration Dates

• First Submitted: April 10, 2019
• First Submitted That Met QC Criteria: April 17, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): August 3, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: GUCY2D
• Additional Relevant MeSH Terms: Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Leber Congenital Amaurosis; Retinal cone dystrophy 2; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Lipids; Polycyclic Compounds; Pyrimidines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Membrane Proteins; Pregnadienetriols; Pregnadienediols; Macrocyclic Compounds; Peptides, Cyclic; Lipopeptides; Polymyxins; Antimicrobial Cationic Peptides; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Prednisone; Prednisolone; Trimethoprim; Polymyxin B
• Other Study ID Numbers: ATSN-101-1; U1111-1200-1308 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes