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

NCT03920007 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: ATSN-101-1U1111-1200-1308
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Leber Congenital Amaurosis; LCA; LCA1

Keywords

GUCY2D

Outcome Measures

Primary Outcomes (2)

• Number of participants with adverse events (AEs) from baseline up to the end of the observation period

  Number of participants with AEs will be summarized in each cohort and overall

  From baseline to week 52

• Number of participants with AEs from baseline up to the end of the safety follow-up period

  Number of participants with AEs will be summarized in each cohort and overall

  From baseline to week 260

Secondary Outcomes (2)

• Change in best -corrected visual acuity (BCVA)

  Baseline to week 52 and Baseline to week 260

• Change in sensitivity

  Baseline to week 52 and Baseline to week 260

Study Arms (1)

ATSN-101

EXPERIMENTAL

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

Drug: ATSN-101; Drug: ATSN-101 Diluent Solution; Drug: Prednisone; Drug: Triamcinalone Acetonide; Drug: 1% Prednisolone; Drug: Trimethoprim/polymyxin B

Interventions

ATSN-101 DRUG

Pharmaceutical form:Solution for intraocular administration Route of administration: Subretinal injection

ATSN-101

ATSN-101 Diluent Solution DRUG

Pharmaceutical form:Solution for parenteral use Route of administration: Subretinal injection

ATSN-101

Prednisone DRUG

Pharmaceutical form:Tablet Route of administration: Oral

ATSN-101

Triamcinalone Acetonide DRUG

Pharmaceutical form:Suspension Route of administration: Peri-ocular injection

ATSN-101

1% Prednisolone DRUG

Pharmaceutical form:Suspension Route of administration: Drops

ATSN-101

Trimethoprim/polymyxin B DRUG

Pharmaceutical form:Solution Route of administration: Topical

ATSN-101

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Atsena Therapeutics Inc.: lead

Study Sites (2)

Casey Eye Institute - Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Scheie Eye Institute, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Leber Congenital Amaurosis; Retinal cone dystrophy 2

Interventions

Prednisone; Prednisolone; Trimethoprim; Polymyxin B

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: April 18, 2019
• Study Start: September 12, 2019
• Primary Completion: May 19, 2023
• Study Completion (Estimated): May 19, 2027
• Last Updated: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

US (2)