Study to Evaluate QR-110 in Leber's Congenital Amaurosis (LCA) Due to the c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation.

Detailed Description
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The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation. Subjects will receive QR-110 in one eye every 3 months, for a maximum of 4 doses. Up to 3 dose levels of QR-110 will be evaluated.

Official Title
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An Open-label, Multiple Dose, Dose Escalation Study to Evaluate the Safety and Tolerability of QR-110 in Subjects With Leber's Congenital Amaurosis (LCA) Due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene

Conditions
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Leber's Congenital Amaurosis

Intervention / Treatment
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* Drug: QR-110


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, ≥ 6 years of age at Screening with a clinical diagnosis of LCA and a molecular diagnosis of homozygosity or compound heterozygosity for the CEP290 p.Cys998X mutation. Best-corrected visual acuity greater than or equal to light perception in both eyes and equal to or worse than LogMAR +1.0 (Snellen notation 20/200) in the worse eye and equal to or worse than LogMAR +0.7 (Snellen notation 20/100) in the contralateral eye. Detectable outer nuclear layer (ONL) in the area of the macula. An electroretinogram (ERG) result consistent with LCA. Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging. Exclusion Criteria: Syndromic disease. Pregnant or breast-feeding female. Any clinically significant cardiac disease or defect. One or more coagulation parameters outside of the normal range. Any ocular disease or condition that could compromise treatment safety, visual acuity or interfere with assessment of efficacy and safety. Prior receipt of intraocular surgery or intravitreal injection within 3 months prior to study start or planned intraocular surgery or procedure during the course of the study. Use of any investigational drug or device within 90 days or 5 half-lives of Day 1, whichever is longer, or plans to participate in another study of a drug or device during the PQ-110-001 study period. Any prior receipt of genetic therapy for LCA

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QR-110<br>Administered every 3 months | Drug: QR-110<br>* RNA antisense oligonucleotide for intravitreal injection<br>* Other names: Sepofarsen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and Severity of Ocular Adverse Events in the Treatment and Contralateral Eyes |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and Severity of Non-ocular Adverse Events |  | 1 year | 
| Change in Best-corrected Visual Acuity (BCVA) |  | 1 year | 
| Change in Full-field Stimulus Test (FST) | Average Red Light Score | 1 year | 
| Change in Full-field Stimulus Test (FST) | Average Blue Light Score | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CEP290, p.Cys998X, c.2991+1655A>G, RNA therapy, Antisense oligonucleotide, Leber's congenital amaurosis